@article {pmid40622765,
year = {2025},
author = {Pesca, C and Lo Iacono, L and Carola, V},
title = {The impact of childhood maltreatment and parental styles on telomere length: the modulatory role of A118G.},
journal = {European journal of psychotraumatology},
volume = {16},
number = {1},
pages = {2521152},
doi = {10.1080/20008066.2025.2521152},
pmid = {40622765},
issn = {2000-8066},
mesh = {Humans ; Female ; Male ; *Parenting/psychology ; Adult ; *Receptors, Opioid, mu/genetics ; Young Adult ; Surveys and Questionnaires ; Child ; *Child Abuse ; *Adult Survivors of Child Abuse ; *Parent-Child Relations ; },
abstract = {Background: Child maltreatment (CM) has been linked to both psychological and biological alterations across the lifespan. While extensive research has addressed the psychological consequences of early adverse experiences, the biological mechanisms - particularly those related to cellular aging - remain less understood. This study examined the effects of different CM types and perceived parenting styles on telomere length (TL), a recognized biomarker of cellular aging, in healthy young adults. Additionally, it explored whether the A118G polymorphism of the μ-opioid receptor gene (OPRM1) moderates these associations.Methods: A sample of 105 healthy young adults participated in the study. Participants completed validated self-report questionnaires assessing CM (Childhood Trauma Questionnaire - Short Form; CTQ-SF) and parental bonding (Parental Bonding Instrument; PBI). Saliva samples were collected for DNA extraction. TL was measured using Real-Time PCR, and A118G (rs1799971) genotyping was conducted via the TaqMan® protocol.Results: Individuals with a history of CM exhibited significantly shorter TL compared to those without such experiences. Specifically, TL showed significant negative correlations with emotional abuse and emotional neglect. Conversely, higher levels of parental care were positively associated with TL. Among parenting styles, the 'affectionless control' pattern - characterized by low care and high overprotection - demonstrated the strongest negative association with TL when reported for both parents. Moreover, the OPRM1 A118G polymorphism moderated the relationship between CM and TL: individuals with the A/A genotype were more vulnerable to TL shortening in the context of CM than G-allele carriers.Conclusion: These findings suggest that CM contributes to accelerated cellular aging and that parenting style, particularly affectionless control, exacerbates this effect. The moderating role of the μ-opioid receptor gene highlights the potential involvement of genetic factors in individual sensitivity to early-life adversity.},
}

Humans
Female
Male
*Parenting/psychology
Adult
*Receptors, Opioid, mu/genetics
Young Adult
Surveys and Questionnaires
Child
*Child Abuse
*Adult Survivors of Child Abuse
*Parent-Child Relations

@article {pmid40619637,
year = {2025},
author = {Beydoun, MA and Noren Hooten, N and Asefa, NG and Georgescu, MF and Song, M and Beydoun, HA and Banerjee, S and Khubchandani, J and Meirelles, O and Launer, LJ and Evans, MK and Zonderman, AB},
title = {Telomere Length, Epigenetic Age Acceleration, and Mortality Risk in US Adult Populations: An Additive Bayesian Network Analysis.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70159},
doi = {10.1111/acel.70159},
pmid = {40619637},
issn = {1474-9726},
support = {/AG/NIA NIH HHS/United States ; },
abstract = {Telomere length and DNA methylation (DNAm) clocks serve as markers of biological aging and have been linked to mortality risk. This study applies additive Bayesian networks (ABNs) to examine associations between DNAm clocks, telomere length, and mortality, with a focus on racial and sex differences in aging. Data from three US cohorts-NHANES (n = 2522), HRS (n = 1029), and HANDLS (n = 92-470)-were analyzed using correlation matrices, Cox models, ABNs, and generalized structural equation models (GSEM) with mortality from the National Death Index. Epigenetic clocks, particularly GrimAgeEAA, HannumAgeEAA, and DunedinPoAM (or DunedinPACE), were stronger mortality predictors than telomere length. ABNs highlighted key relationships, consistently linking age and GrimAgeEAA to mortality in NHANES and HRS. GSEM models derived from ABNs indicated an inverse association between female sex and GrimAgeEAA in NHANES (β = -0.500) and HRS (β = -0.563), suggesting slower biological aging in women, although GrimAge clock incorporates sex in its definition. GrimAgeEAA strongly predicted mortality (LnHR, β ± SE of +0.476 ± 0.0393 in NHANES and +0.511 ± 0.0775 in HRS). Non-Hispanic Black adults exhibited accelerated aging via DunedinPoAM, partially mediating their higher mortality risk. Hispanic adults in NHANES had unique associations with PhenoAgeEAA (β = +0.197), a mortality predictor. DNAm clocks, particularly GrimAgeEAA, outperform telomere length in predicting mortality. Second-generation epigenetic aging markers offer insights into demographic disparities in aging and mortality, with ABNs revealing complex interrelations among aging biomarkers, sex, race, and mortality risk.},
}

@article {pmid40617643,
year = {2025},
author = {Mendez, KJW and Katki, HA and Bupp, C and Spellman, SR and Stewart, DV and Savage, SA and Levine, JE and Saber, W and Aviv, A and Gadalla, SM},
title = {REMOVED: Leukocyte Telomere Shortening in Recipients after Hematopoietic Cell Transplant and Its Association with Factors That Affect Recipient Outcomes: An Analysis of BMT CTN Protocol 1202.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {2S},
pages = {S44},
doi = {10.1016/j.jtct.2025.01.072},
pmid = {40617643},
issn = {2666-6367},
mesh = {Humans ; *Hematopoietic Stem Cell Transplantation/methods/adverse effects ; *Leukocytes/metabolism ; *Telomere Shortening ; Male ; Female ; Adult ; Middle Aged ; },
abstract = {This abstract has been removed: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article has been removed at the request of the author. This abstract has been removed because it was not presented at the 2025 BMT Tandem Meeting.},
}

Humans
*Hematopoietic Stem Cell Transplantation/methods/adverse effects
*Leukocytes/metabolism
*Telomere Shortening
Male
Female
Adult
Middle Aged

@article {pmid40617640,
year = {2025},
author = {Mendez, KJW and Lai, TP and Spellman, SR and Verhulst, S and Anderson, J and Saber, W and Gadalla, SM and Aviv, A},
title = {REMOVED: Long Donor Leukocyte Telomeres Increase the Risk of Severe COVID-19 in Recipients of Allogeneic Hematopoietic Cell Transplant.},
journal = {Transplantation and cellular therapy},
volume = {31},
number = {2S},
pages = {S372},
doi = {10.1016/j.jtct.2025.01.574},
pmid = {40617640},
issn = {2666-6367},
mesh = {Humans ; *COVID-19/etiology ; *Hematopoietic Stem Cell Transplantation/adverse effects ; *Leukocytes/metabolism ; SARS-CoV-2 ; *Telomere/genetics ; Male ; Transplantation, Homologous/adverse effects ; Female ; Middle Aged ; Adult ; Tissue Donors ; Risk Factors ; },
abstract = {This abstract has been removed: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). This article has been removed at the request of the author. This abstract has been removed because it was not presented at the 2025 BMT Tandem Meeting.},
}

Humans
*COVID-19/etiology
*Hematopoietic Stem Cell Transplantation/adverse effects
*Leukocytes/metabolism
SARS-CoV-2
*Telomere/genetics
Male
Transplantation, Homologous/adverse effects
Female
Middle Aged
Adult
Tissue Donors
Risk Factors

@article {pmid40616366,
year = {2025},
author = {He, W and Hu, D and Guo, M and Nie, B and Zhang, G and Jia, Y and Hou, Z and Shu, S and Shao, Y and Simonsen, HT and Twamley, A and Li, C and Wang, L},
title = {The telomere-to-telomere genome of Sanicula chinensis unveils genetic underpinnings of low furanocoumarin diversity and content in one basal lineage of Apiaceae.},
journal = {The Plant journal : for cell and molecular biology},
volume = {123},
number = {1},
pages = {e70311},
doi = {10.1111/tpj.70311},
pmid = {40616366},
issn = {1365-313X},
support = {2023YFA0915802//National Key Research and Development Program of China/ ; JCYJ20241202130723030//Shenzhen Science and Technology Program/ ; 2060302//Innovation Program of Chinese Academy of Agricultural Sciences, Key project at central government level/ ; 32400192//National Natural Science Foundation of China/ ; 32300223//National Natural Science Foundation of China/ ; 32470245//National Natural Science Foundation of China/ ; },
mesh = {*Furocoumarins/metabolism ; *Genome, Plant/genetics ; *Apiaceae/genetics/metabolism ; *Telomere/genetics ; Phylogeny ; Genetic Variation ; },
abstract = {Furanocoumarins are specialized defense compounds in Apiaceae, but the evolutionary path of their biosynthesis is not well understood. We generated a telomere-to-telomere (T2T) genome for Sanicula chinensis, an early-diverging species within the Saniculoideae subfamily, to explore its evolution. Comparative genomics revealed that S. chinensis and Apioideae species each underwent unique whole-genome duplication (WGD). Unlike most species in the Apioideae subfamily, S. chinensis produces a limited diversity and content of furanocoumarins but shows high esculetin levels. This metabolic profile likely stems from three genetic factors: elevated expression of p-Coumaroyl ester 3'-hydroxylase (C3'H) and hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT), which shift the metabolic pathway toward simple coumarins; the absence of a key biosynthetic gene cluster, including prenyltransferase (PT) and p-coumaroyl-CoA 2'-hydroxylase (C2'H), found in Apioideae; and incomplete or inactive PT enzymes in S. chinensis. Our results not only shed light on the evolutionary history of furanocoumarin biosynthesis in Apiaceae, but also provide avenues for tailoring furanocoumarin content for agricultural or medical applications in plants.},
}

*Furocoumarins/metabolism
*Genome, Plant/genetics
*Apiaceae/genetics/metabolism
*Telomere/genetics
Phylogeny
Genetic Variation

@article {pmid40614724,
year = {2025},
author = {Kim, D and Bhargava, R and Wang, SC and Tseng, WC and Lee, D and Patel, R and Oh, S and Bowman, RW and Smith, BA and Kim, M and Na, CH and O'Sullivan, RJ and Miller, KM},
title = {TRIM24 directs replicative stress responses to maintain ALT telomeres via chromatin signaling.},
journal = {Molecular cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molcel.2025.06.009},
pmid = {40614724},
issn = {1097-4164},
abstract = {An inability to replicate the genome can cause replication stress and genome instability. Here, we develop biotinylation of lac operator (LacO) array replication stress protein network identification (BLOCK-ID) in human cancer cells, a proteomic method to identify and visualize proteins at stressed replication forks. This approach identified mediators of the replication stress response, including the chromatin acetylation reader protein tripartite motif containing 24 (TRIM24). We uncovered a crucial role for TRIM24 in coordinating alternative lengthening of telomeres (ALT), a replication stress-directed telomere extension mechanism. Our data reveal that TRIM24 is recruited to telomeres via a p300/CREB binding protein (CBP)-dependent acetylation chromatin signaling cascade to organize the assembly of ALT-associated promyelocytic leukemia (PML) bodies (APBs) and promote de novo telomere DNA synthesis. Tethering of TRIM24 at telomeres was sufficient to stimulate de novo telomere DNA synthesis in a small ubiquitin-like modifier (SUMO)-dependent but p300/CBP- and PML-independent manner. Collectively, these findings uncover an indispensable epigenetic signaling pathway involving TRIM24 and p300/CBP that mediates ALT-telomere maintenance.},
}

@article {pmid40613523,
year = {2025},
author = {Wang, Z and Zhao, C and Huang, Y and Li, C},
title = {Role of telomere maintenance genes as a predictive biomarker for colorectal cancer immunotherapy response and prognosis.},
journal = {Biomolecules & biomedicine},
volume = {},
number = {},
pages = {},
doi = {10.17305/bb.2025.12053},
pmid = {40613523},
issn = {2831-090X},
abstract = {Colorectal cancer (CRC) represents a significant global health challenge. Although telomere maintenance plays a crucial role in tumorigenesis, the prognostic value and immunotherapeutic relevance of telomere maintenance genes (TMGs) in CRC remain poorly understood. In this study, relevant data were retrieved from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. TMG scores were calculated using the single-sample gene set enrichment analysis (ssGSEA) method, and TMGs associated with prognosis were subsequently identified. TCGA-CRC samples were classified into subtypes via consensus clustering (ConsensusClusterPlus). A risk prediction model was then constructed using univariate and Lasso Cox regression analyses. Survival analysis was performed using Kaplan-Meier curves generated with the survival package. Key genes were validated in vitro using cellular models. Immune cell infiltration was evaluated through ssGSEA, TIMER, and MCP-Counter tools, and chemotherapy responses were predicted using the pRRophetic package. From 28 prognosis-related TMGs, two distinct CRC subtypes were established, with subtype C1 demonstrating more favorable clinical outcomes. Additionally, a risk model incorporating seven TMG-related genes (CDC25C, CXCL1, RTL8C, FABP4, ITLN1, MUC12, and ERI1) was developed for CRC prognosis. Differential mRNA expression levels of these genes were confirmed between CRC cell lines and normal control cells. Furthermore, silencing MUC12 suppressed CRC cell migration and invasion in vitro. Importantly, CRC patients classified as low-risk exhibited superior responses to immunotherapy, whereas high-risk patients showed increased sensitivity to conventional anti-cancer treatments. This study represents the first systematic evaluation of TMGs in CRC prognosis and immunotherapy, providing novel insights that could inform personalized therapeutic strategies.},
}

@article {pmid40611236,
year = {2025},
author = {Yang, CH and Huang, MLH and Davis, WA and Jenkins, AJ and Davis, TME},
title = {Determinants of temporal change in telomere length and its associations with chronic complications and mortality in type 2 diabetes: the Fremantle diabetes study phase II.},
journal = {Cardiovascular diabetology},
volume = {24},
number = {1},
pages = {267},
pmid = {40611236},
issn = {1475-2840},
support = {513781 and 1042231//National Health and Medical Research Council/ ; 513781 and 1042231//National Health and Medical Research Council/ ; },
mesh = {Humans ; *Diabetes Mellitus, Type 2/mortality/genetics/diagnosis ; Male ; Female ; Middle Aged ; Time Factors ; Aged ; *Telomere/genetics ; Risk Factors ; Australia/epidemiology ; Risk Assessment ; *Telomere Shortening ; Prognosis ; *Telomere Homeostasis ; Chronic Disease ; Age Factors ; Prospective Studies ; Adult ; },
abstract = {BACKGROUND: Relative telomere length (rTL), a biomarker of biological ageing, has been implicated in type 2 diabetes and its complications. We aimed to identify the associates of rTL change over 4 years (∆rTL), and to investigate whether rTL and ∆rTL are associated with complications and mortality in adults with type 2 diabetes from the Australian observational community-based Fremantle Diabetes Study Phase II (FDS2).

METHODS: Participants (n = 819) from the FDS2 cohort had baseline and Year-4 (mean ± SD 4.2 ± 0.4 years) rTL measured by qPCR (intra- and inter-assay %CV: 0.56% and 2.69%, respectively). The rTL change (∆rTL; % change/year) was categorised as Shortened (< - 2.69%), Unchanged (- 2.69% to + 2.69%) or Lengthened (> + 2.69%). Multiple logistic regression identified clinical and biochemical determinants of ∆rTL Shortened versus Not Shortened (Unchanged plus Lengthened). rTL and ∆rTL (continuous and categorical) were added to Cox and competing risk regression models of conventional predictors of major complications, CVD death and all-cause mortality during a mean ± SD 11.5 ± 2.1 years of follow-up.

RESULTS: rTL was inversely correlated with age (r = - 0.186, P < 0.001). ∆rTL was shortened in 25.5% subjects, unchanged in 10.5%, and lengthened in 64.0%. Shortening was associated with older age, male sex, smoking, obesity, lipid-modifying drug use, and higher platelet count and serum bilirubin levels (P < 0.05). There were no statistically significant unadjusted or age- and sex-adjusted associations between baseline rTL, Year-4 rTL, or ∆rTL, and any incident micro- or macrovascular complications. In unadjusted Cox regression, ∆rTL lengthening was associated with a lower risk of CVD death (hazard ratio 0.98 (0.97, 0.99), P = 0.042) but this association became non-significant after adjustment for conventional risk factors.

CONCLUSIONS: In adults with type 2 diabetes, rTL does not always shorten over time. rTL and ∆rTL were associated with baseline conventional cardiometabolic risk factors but not independently with major incident complications. There was a weak association between ∆rTL and CVD mortality. These findings question the utility of rTL and ∆rTL in usual type 2 diabetes care.},
}

Humans
*Diabetes Mellitus, Type 2/mortality/genetics/diagnosis
Male
Female
Middle Aged
Time Factors
Aged
*Telomere/genetics
Risk Factors
Australia/epidemiology
Risk Assessment
*Telomere Shortening
Prognosis
*Telomere Homeostasis
Chronic Disease
Age Factors
Prospective Studies
Adult

@article {pmid40609992,
year = {2025},
author = {Moskaleva, EY and Glukhov, AI and Zhirnik, AS and Vysotskaya, OV and Vorobiova, SA},
title = {Telomere Length and Telomerase Activity as Biomarkers in the Diagnostics and Prognostics of Pathological Conditions.},
journal = {Biochemistry. Biokhimiia},
volume = {90},
number = {6},
pages = {700-724},
doi = {10.1134/S0006297925600814},
pmid = {40609992},
issn = {1608-3040},
mesh = {Humans ; *Telomerase/metabolism ; *Telomere/metabolism/genetics ; Biomarkers/metabolism ; *Telomere Homeostasis ; Prognosis ; Neoplasms/diagnosis/genetics ; },
abstract = {Telomere biology still remains a topic of interest in life sciences. Analysis of several thousand clinical samples from healthy individuals performed in recent years has shown that the telomere length (TL) in peripheral blood leukocytes correlates with the TL in cells of internal organ and reflects their condition. TL decreases under the influence of damaging factors and can serve as an indicator of health status. The telomere shortening leads to the cell proliferation arrest and is considered as a marker of replicative aging of proliferating cells. A decrease in the TL in peripheral blood leukocytes is viewed as an indicator of organism aging. Recent studies have allowed to formulate the concept on the role of the CST-polymerase α/primase in the C-strand fill in after completion of 3'G overhang synthesis by telomerase during telomere replication. The discovery of the telomeric RNA (TERRA) and its role in the regulation of telomerase activity (TA) and alternative lengthening of telomeres, as well as the possibility of TERRA translation, has provided evidence of the complex epigenetic regulation of the TL maintenance. Analysis of the published data indicates that telomeres are dynamic structures, whose length undergoes significant changes under the influence of damaging factors. TL is determined not only by the chronological age, but also by the exposure to the exogenous and endogenous deleterious factors during the lifetime. A decrease in the TL due to inherited mutations in the genes coding for proteins involved in the telomere structure formation and telomere replication (primarily, proteins of the shelterin and CST complexes and telomerase) has been found in a number of hereditary diseases - telomeropathies. The assessment of TL and TA is of great importance for the diagnostics of telomeropathies and can be useful in the diagnostics of cancer. Analysis of TL can be used for monitoring the health status (e.g., in the case of exposure to ionizing radiation and space flight factors), as well as predicting individual's sensitivity to the action of various damaging agents. The application of modern advancement in genetic technologies in the analysis of TL and TA makes it available for the use in clinical and epidemiological studies, diagnostics of telomeropathies, and monitoring of astronauts' health.},
}

Humans
*Telomerase/metabolism
*Telomere/metabolism/genetics
Biomarkers/metabolism
*Telomere Homeostasis
Prognosis
Neoplasms/diagnosis/genetics

@article {pmid40609742,
year = {2025},
author = {Toor, AA and Horton, M and Khalid, H and Krieger, E and Lai, TP and Spellman, SR and Levine, JE and Saber, W and Stewart, V and Gadalla, SM},
title = {Understanding Telomere Biology in Hematopoietic Cell Transplantation: A Dynamical Systems Perspective.},
journal = {Transplantation and cellular therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jtct.2025.06.024},
pmid = {40609742},
issn = {2666-6367},
abstract = {BACKGROUND: . T cell proliferation and repertoire reconstitution is a hallmark of successful hematopoietic cell transplantation (HCT). This process may be modeled as a dynamical system and in such a system, precise telomere length (TL) measurement may reflect the proliferative capacity of donor T cells. TL for different chromosomes span a few orders of magnitude, and different blood cell populations including T cell clones display variable TL; these differences across the cell populations are not represented when examining average leukocyte TL. This study aims to develop a method that integrates the entire spectrum of TL observed within a sample to better understand the influence on clinical outcomes following HCT.

METHODS: . To better reflect the entire span of TL, we used data generated using the Telomere Shortest Length Assay (TeLSA) that provides discrete measurements of individual telomeres for each blood DNA sample. TeSLA leukocyte TL (LTL) measurements were performed on 72 paired samples collected from the donor pre-transplant (D-LTL) and the recipient 90 days following HCT (post-HCT LTL). Area under the curve (AUC) calculations were used to incorporate the full distribution of measured LTL from each sample. The magnitude of LTL shortening after HCT was calculated as the difference between the AUCs for D-LTL and corresponding post-HCT LTL, and referred to as AUC delta-TL.

RESULTS: . Telomere band lengths ranged from 350 base pairs to 16.7 kilobases with a logarithmically declining distribution in all samples when arrayed in descending order. The AUC delta-TL predicted patient overall survival (OS; P-log rank <0.0001); HCT recipients with an intermediate degree of TL shortening (25[th]-75[th] percentile/Q2&3) post-HCT experienced the best outcomes (2 years OS =92%), whilst donors with minimal (<25[th] percentile/Q1; 2 years OS=33%; adjusted HR vs. intermediate shortening=9.3, p=0.001) or maximal (>75[th] percentile/Q4; 2 years OS=59%; adjusted HR=6.0, p=0.01) TL shortening had worse outcomes.

CONCLUSION: . The findings described herein suggest that the degree of donor telomere attrition may correlates with clinical outcomes following transplant, possibly reflecting alloreactive T cell expansion. Accounting for the entire span of telomere lengths, may better identify post-transplant risk groups.},
}

@article {pmid40606259,
year = {2024},
author = {Mansoubi, S and Mohsenpour, M},
title = {Comparison of Telomere Structure in Eukaryotes.},
journal = {Archives of Razi Institute},
volume = {79},
number = {6},
pages = {1365-1374},
pmid = {40606259},
issn = {2008-9872},
mesh = {*Telomere/chemistry/ultrastructure ; *Saccharomyces cerevisiae/genetics ; Animals ; Humans ; Telomere-Binding Proteins/metabolism ; Saccharomyces cerevisiae Proteins ; Mammals/genetics ; },
abstract = {Telomeres are DNA-protein complexes that are located at the ends of eukaryotic chromosomes. The fusion of broken chromosome ends is prevented by the presence of telomeres, which act to inhibit this process. This specific function of telomeres serves to distinguish normal chromosome ends from double-stranded breaks in DNA. Telomeres contain a series of short, repeated sequences arranged in a tandem array. The number of repeats varies between different organisms, with a range of 20 to 1,000 repeats being typical. A G-rich strand is replicated by lagging strand synthesis, which creates a 3' overhang. In addition, a complementary C-rich strand is replicated by leading strand synthesis. The objective of this study is to undertake a comparative analysis of the structure of telomeres in Saccharomyces cerevisiae, Saccharomyces pombe and mammals. In Saccharomyces cerevisiae, the Rap1 protein binds to the double-stranded telomeric sequences, as well as to the Rif1 and Rif2 proteins, which regulate telomere length. Cdc13 and the Cdc13-interacting factors Ten1 and Stn1 bind to the single-stranded overhang. In Saccharomyces pombe telomeres, Taz1 binds to the double-stranded DNA (dsDNA), and Rap1 and Rif1 also bind to the ds region via Taz1. Pot1 interacts with Tpz1, forming a complex that binds to the 3' overhang. The protein Poz1 serves to connect the dsDNA binding complex, comprising Taz1 and Rap1, to the ssDNA binding complex, which includes Pot1 and Tpz1. Furthermore, Ccq1 interacts with Tpz1 and facilitates the recruitment of telomerase. The Stn1/Ten1 complex exhibits a binding affinity for a single-stranded telomere. In mammalian telomeres, the shelterin complex that binds double-stranded telomeric DNA is composed of six subunits. The double-stranded telomeric DNA is bound by TRF1 and TRF2. TPP1 and POT1 are capable of binding single-stranded DNA. TIN2 serves to connect the dsDNA binding complex TRF1/TRF2 to the ssDNA binding complex POT1/TPP1. Rap1 binds to the telomere by interacting with TRF1 and TRF2. Moreover, this study will address the regulation and comparison of the shelterin complex. Additionally, in mammals, the activation of DNA damage response pathways is necessary when double-strand DNA is broken. This, in turn, elucidates the specific repair pathways that are employed. We conclude by discussing the T-loop structure, as telomeres in several species have been shown to fold back into a structure called a T-loop, which is believed to mediate telomere protection.},
}

*Telomere/chemistry/ultrastructure
*Saccharomyces cerevisiae/genetics
Animals
Humans
Telomere-Binding Proteins/metabolism
Saccharomyces cerevisiae Proteins
Mammals/genetics

@article {pmid40601421,
year = {2025},
author = {Liu, H and Zhang, JQ and Tao, JP and Chen, C and Su, LY and Xiong, JS and Xiong, AS},
title = {A telomere-to-telomere gapless genome reveals SlPRR1 control of circadian rhythm and photoperiodic flowering in tomato.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
pmid = {40601421},
issn = {2047-217X},
support = {32402552//National Natural Science Foundation of China/ ; BK20221009//Natural Science Foundation of Jiangsu Province/ ; BE2023350//Key Research and Development Program of Jiangsu/ ; ZR2021QC018//Shandong Provincial Natural Science Foundation/ ; //Nanjing Agricultural University/ ; },
mesh = {*Solanum lycopersicum/genetics/physiology/growth & development ; *Photoperiod ; *Circadian Rhythm/genetics ; *Flowers/genetics/growth & development ; *Genome, Plant ; *Plant Proteins/genetics/metabolism ; *Telomere/genetics ; Phylogeny ; Gene Expression Regulation, Plant ; Genomics/methods ; },
abstract = {Cultivated tomato (Solanum lycopersicum) is a major vegetable crop of high economic value that serves as an important model for studying flowering time in day-neutral plants. A complete, continuous, and gapless genome of cultivated tomato is essential for genetic research and breeding programs. Here, we report the construction of a telomere-to-telomere (T2T) gap-free genome of S. lycopersicum cv. VF36 using a combination of sequencing technologies. The 815.27-Mb T2T "VF36" genome contained 600.23 Mb of transposable elements. Through comparative genomics and phylogenetic analysis, we identified structural variations between the "VF36" and "Heinz 1706" genomes and found no evidence of a recent species-specific whole-genome duplication in the "VF36" tomato. Furthermore, a core circadian oscillator, SlPRR1, was identified, which peaked at night in a circadian rhythm. CRISPR/Cas9-mediated knockdown of SlPRR1 in tomatoes demonstrated that slprr1 mutant lines exhibited significantly earlier flowering under long-day condition than wild type. We present a hypothetical model of how SlPRR1 regulates flowering time and chlorophyll biosynthesis in response to photoperiod. This T2T genomic resource will accelerate the genetic improvement of large-fruited tomatoes, and the SlPRR1-related hypothetical model will enhance our understanding of the photoperiodic response in cultivated tomatoes, revealing a regulatory mechanism for manipulating flowering time.},
}

*Solanum lycopersicum/genetics/physiology/growth & development
*Photoperiod
*Circadian Rhythm/genetics
*Flowers/genetics/growth & development
*Genome, Plant
*Plant Proteins/genetics/metabolism
*Telomere/genetics
Phylogeny
Gene Expression Regulation, Plant
Genomics/methods

@article {pmid40600342,
year = {2025},
author = {Wolf, SE and George, EM and Dong, J and Rosvall, KA},
title = {Telomere-Related Gene Networks in the Ovary Shift Across Environmental Factors.},
journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jez.70003},
pmid = {40600342},
issn = {2471-5646},
support = {//S.E.W. was supported by a Bruce McEwen Career Development Fellowship from the Social Dimensions of Health and Aging Research Network (NIH R24 AG065172), the NIH training program T32 HD049336, and the Center for the Integrative Study of Animal Behavior. E.M.G. was supported by an NSF graduate research fellowship, the NIH training program T32 HD049336, the Animal Behavior Society, and McKinley Research Fund. Additional support from NSF IOS-1656109 and IOS-1942192 to K.A.R., with Research Support for Postbaccalaureates for J.D./ ; },
abstract = {The ovary is key to linking environmental factors with the timing and quality of offspring development. Focused on free-living female tree swallows (Tachycineta bicolor), we measured temporal variation in ovarian expression of genes involved in the regulation of telomere length. Using qPCR, we quantified mRNA abundance of shelterin proteins (TERF1, TERF2, TERF2IP, TPP1, POT1), telomerase (TERT), antioxidants (SOD1, PRDX-1, GPX), and glucocorticoid receptors (MR, GR). We asked how they differ across breeding stages and social environments, and then we assessed effects on gene co-expression, which reflects coordinated changes across this network of interacting genes. We hypothesized that maintenance of telomeres is upregulated and more strongly coregulated in the lead up to reproduction, i.e., before egg-laying and following a social challenge. We did not find a main effect of environmental context on mRNA abundance, but we did detect subtle differences in gene co-expression networks. Females exhibited stronger coregulation among shelterin proteins and stronger crosstalk with glucocorticoid receptors during incubation. In response to a conspecific challenger, coregulation of antioxidants with shelterin and glucocorticoid receptors was weaker or more negatively correlated, suggesting semi-independent social modulation of these telomere regulatory networks. While the consequences of these transcriptional differences require more research, our results suggest that the environment could contribute to protection of the ovary, including its telomeres.},
}

@article {pmid40596487,
year = {2025},
author = {Yamauchi, S and Ecoff, K and Gurau, A and Rodgers, KP and Brock, MV and Mei, Y},
title = {TERT PfeRNA regulates telomere length during cellular senescence of normal human bronchial epithelial cells.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {21838},
pmid = {40596487},
issn = {2045-2322},
support = {CA259658/NH/NIH HHS/United States ; },
mesh = {Humans ; *Telomerase/metabolism/genetics ; *Cellular Senescence/genetics ; *Epithelial Cells/metabolism/cytology ; *Bronchi/cytology/metabolism ; *Telomere/metabolism/genetics ; *Telomere Homeostasis ; Cell Line ; Cell Proliferation ; },
abstract = {Telomeres progressively shorten with each cell division in human somatic cells, but the mechanisms governing telomere length remain incompletely understood. Although telomerase reverse transcriptase (TERT) is central to telomere maintenance, the discrepancy between TERT level and telomere length highlights the unidentified molecules that regulate TERT's functional activities. Here, we identify novel TERT-associated protein functional effector sncRNAs (TpfeRNAs) that modulate telomerase activity and telomere length during cellular senescence of normal human bronchial epithelial (NHBE) cells. We found that in senescent NHBE cells, telomerase activity, TERT mRNA levels, and telomere length were 60%, 2.7%, and 76% of those in proliferative cells, respectively. Using immunoprecipitation and TA cloning assays, we identified TpfeRNAa and TpfeRNAb, which were differentially expressed in proliferative and senescent NHBE cells. Blocking TpfeRNAb in senescent cells increased telomere length by 18% and boosted telomerase activity by tenfold, while ectopic expression of TpfeRNAb in proliferative decreased telomere length by 10%. These findings uncover TpfeRNAb as a key regulator of TERT activity to control telomere length, providing new insights into cellular senescence and aging-related diseases.},
}

Humans
*Telomerase/metabolism/genetics
*Cellular Senescence/genetics
*Epithelial Cells/metabolism/cytology
*Bronchi/cytology/metabolism
*Telomere/metabolism/genetics
*Telomere Homeostasis
Cell Line
Cell Proliferation

@article {pmid40595131,
year = {2025},
author = {Ismail, A and Jaalouk, K and Koteish, J and Tarhini, Y and Sadier, NS and Abou-Abbas, L and Jaalouk, K},
title = {Exploring the association between depression and telomere length: A systematic review and meta-analysis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {22967},
pmid = {40595131},
issn = {2045-2322},
mesh = {Humans ; *Telomere/genetics ; *Depressive Disorder, Major/genetics ; *Depression/genetics ; *Telomere Homeostasis ; *Telomere Shortening ; Male ; },
abstract = {Telomere length has emerged as a potential biomarker of cellular aging and has been implicated in various psychiatric disorders, including depression. However, recent studies investigating the association between depression and telomere length have yielded inconsistent findings. The objective of this study is to systematically review the current literature to evaluate the correlation between depression and telomere length, while also examining the influence of potential moderators such as age, gender, assessment techniques, tissue resources, and depression assessment protocols on this association. We systematically included studies measuring telomere length in individuals meeting clinical or rating scale thresholds for Major Depressive Disorder (MDD), employing a thorough search strategy across PubMed, Embase, PsycINFO, and Google Scholar. Using a structured data abstraction form, studies were meticulously assessed for inclusion or exclusion based on predetermined criteria. Analysis involved standardized mean differences within a random effects model framework, allowing for a comprehensive examination of the association between depression and telomere length while accounting for heterogeneity across studies. Following the meticulous screening of titles, abstracts, and full texts, a total of 71 articles meeting our inclusion criteria were identified and included in the meta-analysis. Our analysis revealed a significant association between depression and telomere length, with a Cohen's d effect size of -0.354 (p-value < 0.0001, I[2] = 80%). Subgroup analysis uncovered significant influences of various factors on the relationship between depression and telomere length, including depression assessment tools, measurement scales, telomere measurement techniques, source tissue, and the presence of comorbid medical conditions. Moreover, multivariable meta-regression showed that age, depression measurement technique, and telomere measurement technique significantly impacted this association. Our findings underscore the complexity of the relationship between depression and telomere length and emphasize the importance of considering multiple factors when interpreting study outcomes. Further studies are necessary to elucidate the potential causality underlying this association and to explore the bidirectional connection between depression severity and telomere shortening.},
}

Humans
*Telomere/genetics
*Depressive Disorder, Major/genetics
*Depression/genetics
*Telomere Homeostasis
*Telomere Shortening
Male

@article {pmid40593584,
year = {2025},
author = {Sobinoff, AP and Wells, JK and Chow, M and Nelson, CB and Wu, X and Cohen, SB and Lau, YH and Bryan, TM and Fox, A and Pickett, HA},
title = {NONO, SFPQ, and PSPC1 promote telomerase recruitment to the telomere.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {5769},
pmid = {40593584},
issn = {2041-1723},
support = {2003250//Department of Health | National Health and Medical Research Council (NHMRC)/ ; ECF171269//Cancer Institute NSW (Cancer Institute New South Wales)/ ; },
mesh = {*Telomerase/metabolism/genetics ; Humans ; *Telomere/metabolism ; Animals ; *RNA-Binding Proteins/metabolism/genetics ; *DNA-Binding Proteins/metabolism/genetics ; *Drosophila Proteins/metabolism/genetics ; HEK293 Cells ; *Nuclear Proteins/metabolism/genetics ; PTB-Associated Splicing Factor/metabolism/genetics ; Coiled Bodies/metabolism ; RNA/metabolism ; Molecular Chaperones ; },
abstract = {Telomerase is a ribonucleoprotein enzyme that maintains telomeric repeats on chromosome ends in continuously dividing cells. Telomere maintenance via telomerase is dependent on the correct assembly of the enzyme complex, complex stabilization by associated cofactors, and effective recruitment to the telomere. Here, we show that telomerase is regulated in each of these processes by the Drosophila behaviour/human splicing (DBHS) family of RNA/DNA binding proteins (NONO, SFPQ and PSPC1). The DBHS proteins associate with catalytically active telomerase through the hTR RNA template component. Cells lacking the DBHS proteins display telomerase retention in nuclear Cajal bodies and impaired telomerase recruitment to the telomere, with NONO and PSPC1 depletion culminating in progressive telomere shortening in several cell lines, with the exception of long-term NONO depletion in 293 and 293T. Our results reveal the DBHS protein family as components of the telomerase trafficking machinery integral to telomere maintenance.},
}

*Telomerase/metabolism/genetics
Humans
*Telomere/metabolism
Animals
*RNA-Binding Proteins/metabolism/genetics
*DNA-Binding Proteins/metabolism/genetics
*Drosophila Proteins/metabolism/genetics
HEK293 Cells
*Nuclear Proteins/metabolism/genetics
PTB-Associated Splicing Factor/metabolism/genetics
Coiled Bodies/metabolism
RNA/metabolism
Molecular Chaperones

@article {pmid40593162,
year = {2025},
author = {Tournoy, TK and Martens, DS and De Backer, J and Coucke, P},
title = {How sample handling distorts telomere studies.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {20427},
pmid = {40593162},
issn = {2045-2322},
support = {12X9623N//Fonds Wetenschappelijk Onderzoek/ ; G072022N//Fonds Wetenschappelijk Onderzoek/ ; },
mesh = {Humans ; *Telomere/genetics ; Male ; Female ; Adult ; Middle Aged ; *Specimen Handling/methods ; *Telomere Homeostasis ; Aged ; Reproducibility of Results ; Real-Time Polymerase Chain Reaction ; *Blood Specimen Collection/methods ; },
abstract = {Telomere length (TL) is investigated as a biomarker for aging and disease-susceptibility, but measurement using quantitative polymerase chain reaction (qPCR) faces challenges in accuracy and reproducibility. The potential impact of pre-analytical factors on TL measurements remains underexplored. We evaluated the impact of delayed blood processing, a typical feature in population studies. Blood samples from 35 adults were processed for buffy coat extraction either immediately or kept at 4 °C and processed after three and seven days (total n = 105). After processing, samples were stored at -80 °C. Relative TL was measured via qPCR and expressed as T/S ratio. Strikingly, delayed blood processing led to a significant increase in TL: the mean T/S ratio was 0.886 ± 0.205 at day 0, rising to 1.022 ± 0.240 at day 3 (p = 0.03) and to 1.190 ± 0.205 at day 7 (p < 0.001), corresponding to increases of 15% and 34%, respectively. Notably, TL correlated inversely with DNA integrity. These findings underscore the critical impact of delayed sample processing on TL measurements, emphasizing the need for consistent pre-analytical protocols to ensure accurate and reliable research outcomes. The impact of our findings is considerable as it may overshadow not only previously reported results but also real biological differences in TL between studied groups of patients.},
}

Humans
*Telomere/genetics
Male
Female
Adult
Middle Aged
*Specimen Handling/methods
*Telomere Homeostasis
Aged
Reproducibility of Results
Real-Time Polymerase Chain Reaction
*Blood Specimen Collection/methods

@article {pmid40592147,
year = {2025},
author = {Zhang, S and Chen, H and Li, L and Li, Z and Wang, D},
title = {Exposure to placental microplastic and placental and umbilical cord blood telomere length.},
journal = {Ecotoxicology and environmental safety},
volume = {302},
number = {},
pages = {118536},
doi = {10.1016/j.ecoenv.2025.118536},
pmid = {40592147},
issn = {1090-2414},
abstract = {Exposure to microplastics poses potential risks to human health, particularly during pregnancy and early life; however, research in this field remains scarce. Therefore, we aimed to investigate the association between prenatal microplastic exposure and telomere length (TL), a recognized marker of biological aging. Placental microplastic exposure and its potential effects on umbilical cord blood TL and placental tissues were investigated in a cohort of 1121 pregnant women from Shenyang, China. Microplastic concentrations in placental samples were quantified using LD-IR chemical imaging, while TL in umbilical cord blood and placental tissues was measured using qRT-PCR. Adjusted multivariable regression models, stratified analysis, and mixture analyses, including Bayesian Kernel Machine Regression (BKMR) and quantile g-computation, were employed to assess associations and interactions. Placental microplastics (particularly polyvinyl chloride (PVC), polypropylene (PP), and polybutylene succinate (PBS)), were prevalent, with median total concentrations of 15 n/10 g of placental tissue. In cord blood, higher PVC and PBS levels were significantly associated with reduced TL (adjusted β = -0.13 and -0.14, respectively; p ≤ 0.01). PP exposure showed no significant association with cord blood TL. For placental TL, all three microplastics demonstrated significant negative associations, with PP showing the strongest effect (β = -0.13, p < 0.001). Stratified analysis revealed no sex-based differences in associations. Quantile g-computation indicated significant cumulative effects of microplastics on TL, with PBS contributing the most to TL reduction. BKMR analysis highlighted non-linear exposure-response relationships, with lower quantiles showing positive associations and higher quantiles indicating detrimental effects on TL, potentially due to oxidative stress or inflammation. These findings underscore the pervasive presence of microplastics in placental tissues and their potential role in disrupting telomere maintenance, raising concerns about their long-term health implications for newborns.},
}

@article {pmid40585571,
year = {2025},
author = {Aoyagi Blue, Y and Iimura, H and Sato, MP and Shirasawa, K},
title = {The impact of telomere-to-telomere genome assembly in the plant pan-genomics era.},
journal = {Breeding science},
volume = {75},
number = {1},
pages = {3-12},
pmid = {40585571},
issn = {1344-7610},
abstract = {Advances in sequencing technologies have enabled the determination of genome sequences of multiple lines within a single species. Comparative analysis of multiple genome sequences reveals all genes present within a species, providing insight into the genetic mechanisms that lead to the establishment of species. Highly accurate pan-genome analysis requires telomere-to-telomere gapless genome assembly, providing an ultimate genome sequence that covers all chromosomal regions without any undetermined nucleotide sequences. This review describes the genome sequencing technologies and sophisticated bioinformatics required for telomere-to-telomere gapless genome assembly, as well as a genetic mapping that can evaluate the accuracy of telomere-to-telomere genome assembly. Pan-genome analyses may contribute to the understanding of genetic mechanisms not only within a single species but also across species.},
}

@article {pmid40578221,
year = {2025},
author = {Majumdar, V and Kumar, PB and Arasappa, R and Hegde, S and Manjunath, NK and Chakraborty, P and Murugesh, K and Palanisamy, A and Jose, A},
title = {The mediating influence of serum Klotho levels and the KL-VS heterozygosity on telomere shortening in schizophrenia.},
journal = {Schizophrenia research},
volume = {282},
number = {},
pages = {166-175},
doi = {10.1016/j.schres.2025.06.013},
pmid = {40578221},
issn = {1573-2509},
abstract = {Schizophrenia (SZ) has a considerable contribution of accelerated aging, and exploration of the mechanistic underpinnings of telomere attrition, one of the core pathophysiological hallmarks of accelerated aging could boost the development of new avenues for intervention in SZ. The longevity protein Klotho (KL) is reported to regulate the expression of key factors like telomeric repeat-binding factor. We tested the cross-sectional association between KL levels, its longevity genetic variant KL-VS and telomere length in schizophrenia, including 240 patients and 243 healthy controls (HCs). Relative telomere length (rTL) was measured through real-time polymerase chain reaction, and the KL-VS variant was genotyped using TaqMan® allelic discrimination assay. The associations between study variables were tested using linear regression, and mediation analysis was conducted using the SPSS Macro PROCESS. There was a significant association between rTL with serum KL levels in chronic patients, indicating their coregulation in the disease. KL levels partly mediated the indirect negative influence of telomere length on the risk of schizophrenia, with a 27.26 % contribution to the total association between telomere length and schizophrenia, substantiating the role of deficiency of circulating Klotho in partly contributing to the process of accelerated aging in schizophrenia. Furthermore, serum KL levels and heterozygosity of the KL-VS variant (Het[+ve]) were significantly and positively associated with rTL in patients with SZ, but not in HCs, indicating a disease-specific influence of the KL on telomere length, which supports the hypothesis of a contextual advantage.},
}

@article {pmid40575787,
year = {2025},
author = {Li, S and Zhang, L and Zhang, H},
title = {Corrigendum: A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma.},
journal = {Frontiers in pharmacology},
volume = {16},
number = {},
pages = {1600217},
doi = {10.3389/fphar.2025.1600217},
pmid = {40575787},
issn = {1663-9812},
abstract = {[This corrects the article DOI: 10.3389/fphar.2024.1532610.].},
}

@article {pmid40573115,
year = {2025},
author = {Polom, J and Boccardi, V},
title = {Employing Nutrition to Delay Aging: A Plant-Based Telomere-Friendly Dietary Revolution.},
journal = {Nutrients},
volume = {17},
number = {12},
pages = {},
pmid = {40573115},
issn = {2072-6643},
mesh = {Humans ; *Telomere/metabolism ; *Aging ; Telomere Shortening ; Oxidative Stress ; Antioxidants ; *Diet ; Telomerase/metabolism ; },
abstract = {Telomere attrition is a hallmark of cellular aging, influenced by oxidative stress, chronic inflammation, and metabolic dysregulation. Emerging evidence suggests that dietary patterns rich in plant-based, minimally processed foods may influence telomere dynamics, potentially extending healthspan. This narrative review synthesizes current literature on the molecular mechanisms by which specific nutrients-such as antioxidants, polyphenols, omega-3 fatty acids, and methyl donors-affect telomere length and telomerase activity. Conversely, high consumption of ultra-processed foods (UPFs) has been associated with accelerated telomere shortening and dysfunction, likely due to increased oxidative stress, inflammation, and nutrient deficiencies. We propose a tiered dietary intervention model including preventive, therapeutic, and regenerative phases, tailored to individual aging trajectories and physiological statuses. This model emphasizes the consumption of whole plant foods, functional bioactives, and the reduction of UPFs to preserve telomere integrity. Implementing such dietary strategies may offer a viable approach to mitigate age-related cellular decline and promote healthy aging.},
}

Humans
*Telomere/metabolism
*Aging
Telomere Shortening
Oxidative Stress
Antioxidants
*Diet
Telomerase/metabolism

@article {pmid40573097,
year = {2025},
author = {Kim, M and Baik, I},
title = {Effects of Hawthorn Fruit Supplementation on Facial Skin Phenotypes and Leukocyte Telomere Length Stratified by TERT Polymorphisms.},
journal = {Nutrients},
volume = {17},
number = {12},
pages = {},
doi = {10.3390/nu17121983},
pmid = {40573097},
issn = {2072-6643},
support = {RS-2024-00336637//National Research Foundation of Korea Grant/ ; },
mesh = {Humans ; Female ; Middle Aged ; Male ; *Telomerase/genetics ; Aged ; *Dietary Supplements ; Double-Blind Method ; *Leukocytes/drug effects ; Adult ; *Skin Aging/drug effects ; *Crataegus/chemistry ; Phenotype ; *Fruit ; *Telomere ; *Polymorphism, Single Nucleotide ; *Skin/drug effects ; Face ; *Telomere Homeostasis ; },
abstract = {OBJECTIVES: A randomized, double-blind, placebo-controlled intervention study aimed to evaluate whether hawthorn fruit (HF) supplementation can influence facial skin phenotypes and leukocyte telomere length (TL) and whether these effects differ by genetic polymorphisms related to TL.

PARTICIPANTS/METHODS: Among 41 male and female adults aged 25-75 years who participated in the study, 36 completed initial and follow-up examinations over 6 months. The HF supplementation group (n = 17) was instructed to take a powdered HF supplement (900 mg/day), while controls (n = 19) were to take a cornstarch placebo (900 mg/day). Facial skin phenotypes, including pigmentation, pores, hydration, wrinkles, and elasticity, were measured before and after the intervention, and changes in these phenotype scores were calculated. Sequencing of telomerase reverse transcriptase (TERT) polymorphisms, such as rs7705526 (C>A) and rs2853669 (A>G), was conducted.

RESULTS: The HF supplementation group exhibited significantly improved hydration scores compared to the control group; the mean changes (follow-up measure-baseline measure) [standard deviation] in hydration scores over 6 months were 1.71 [8.18] and -3.00 [8.42] for the supplementation group and control group, respectively (p < 0.05) (Cohen's d = 0.57). However, changes in other phenotypes and leukocyte TL were similar between groups. The genotype-specific analysis revealed that the improvement of hydration state was most noticeable among carriers with the CC genotype of rs7705526 (p < 0.05) (Cohen's d = 1.50) and that the HF supplementation group exhibited reduced wrinkle scores while the control group showed increased scores among carriers of the AA genotype of rs2853669 (p < 0.05) (Cohen's d = 1.40). In correlation analysis for all participants, hydration scores were positively correlated with leukocyte TL (Spearman correlation coefficient: 0.36; p < 0.05).

CONCLUSIONS: These findings suggest that HF consumption may have potential anti-skin-aging effects. Future studies may need to elucidate the biological mechanisms underlying these effects.},
}

Humans
Female
Middle Aged
Male
*Telomerase/genetics
Aged
*Dietary Supplements
Double-Blind Method
*Leukocytes/drug effects
Adult
*Skin Aging/drug effects
*Crataegus/chemistry
Phenotype
*Fruit
*Telomere
*Polymorphism, Single Nucleotide
*Skin/drug effects
Face
*Telomere Homeostasis

@article {pmid40568934,
year = {2025},
author = {Mender, I and Girotti, R and Gryaznov, S},
title = {Novel telomere-targeting dual-pharmacophore dinucleotide prodrugs for anticancer therapy.},
journal = {Nucleic acids research},
volume = {53},
number = {12},
pages = {},
pmid = {40568934},
issn = {1362-4962},
support = {//MAIA Biotechnology, Inc/ ; },
mesh = {*Prodrugs/pharmacology/chemistry/chemical synthesis/therapeutic use ; *Telomere/drug effects/metabolism ; Humans ; Animals ; *Antineoplastic Agents/pharmacology/chemistry/chemical synthesis/therapeutic use ; Mice ; Cell Line, Tumor ; *Telomerase/antagonists & inhibitors/metabolism ; Deoxyuridine/analogs & derivatives/pharmacology/chemistry ; Neoplasms/drug therapy ; Thionucleosides/chemistry/pharmacology ; Pharmacophore ; },
abstract = {Telomerase is an attractive therapeutic target due to its expression in most cancer cells. This study focuses on harnessing the potential of telomerase to alter telomeres as a therapeutic modality. We designed and synthesized divalent dinucleotide prodrugs comprised of 6-thio-2'-deoxyguanosine (6-thio-dG; THIO) and 5-fluoro-2'-deoxyuridine (5-FdU) nucleosides. Although dinucleotides containing 5-FdU pharmacophores showed better activity in vitro versus compounds containing only THIO pharmacophores, we observed greater activity for THIO-containing compounds in vivo. The homopurine compounds MAIA-2022-12 and MAIA-2021-20, with two 6-thio-dG pharmacophores, linked by 3', 5'- and 5', 5'-phosphodiester bonds, respectively, demonstrated the greatest anticancer efficacy among the compounds tested and induced host immune-memory responses in vivo. The sequential combination of MAIA-2022-12 or MAIA-2021-20 with the immune anti-PD-1 or anti-PD-L1 checkpoint inhibitors demonstrated superior anticancer efficacy compared with the corresponding monotherapies. We conclude that MAIA-2022-12 and MAIA-2021-20 are promising candidates for future preclinical and potential clinical studies.},
}

*Prodrugs/pharmacology/chemistry/chemical synthesis/therapeutic use
*Telomere/drug effects/metabolism
Humans
Animals
*Antineoplastic Agents/pharmacology/chemistry/chemical synthesis/therapeutic use
Mice
Cell Line, Tumor
*Telomerase/antagonists & inhibitors/metabolism
Deoxyuridine/analogs & derivatives/pharmacology/chemistry
Neoplasms/drug therapy
Thionucleosides/chemistry/pharmacology
Pharmacophore

@article {pmid40567516,
year = {2025},
author = {She, JS and Liu, R and Mao, SQ and Zhou, BK and Wu, XJ and Ding, MZ and Wang, LX and Cao, YN and Wu, HY and Long, YH and Guo, F and Huang, HF and Gao, L},
title = {Causal relationships between leukocyte telomere length and female reproductive system diseases: a bidirectional Mendelian randomization study.},
journal = {Reproductive and developmental medicine},
volume = {9},
number = {2},
pages = {83-91},
pmid = {40567516},
issn = {2589-8728},
abstract = {OBJECTIVE: Although numerous observational studies have revealed a correlation between leukocyte telomere length (LTL) and female reproductive system diseases (RSDs), the findings of these studies have tended to be consistent. In this study, we accordingly sought to clarify the causal relationships between LTL and RSDs.

METHODS: We performed a bidirectional two-sample Mendelian randomization (MR) analysis using pooled statistics from genome-wide association studies of LTL and nine female RSDs. The final results were analyzed using five MR methods, with the inverse variance weighted (IVW) method used as the primary outcome. We applied MR-PRESSO to exclude outliers. Sensitivity analyses were also conducted to assess heterogeneity and pleiotropy.

RESULTS: In the forward MR analysis, a genetic prediction of longer LTLs was found to be causally associated with higher risks of endometriosis (IVW: odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.06-1.46, P = 0.008), leiomyoma of the uterus (IVW: OR = 1.73, 95% CI = 1.52-1.98, P = 4.9E-16), and ovarian cysts (IVW: OR = 1.31, 95% CI:1.19-1.45, P = 1.5E-07). In the reverse MR results, female RSDs were shown to have no significant effect on LTLs (all P values >0.05). Sensitivity analysis confirmed the robustness of these results.

CONCLUSIONS: Our findings substantiate the assumption that a genetically predicted longer LTL elevates the risk of endometriosis, leiomyoma of the uterus, and ovarian cysts, with no influence of RSDs on LTL. These findings contribute to establishing a causal link between LTL and RSDs, overcoming the constraints of earlier observational studies. They also imply that LTL could potentially serve as a biomarker for the occurrence of endometriosis, leiomyoma of the uterus, and ovarian cysts.},
}

@article {pmid40566527,
year = {2025},
author = {Baliou, S and Apetroaei, MM and Hatzidaki, E and Kuzmin, SV and Tzatzarakis, MN and Arsene, AL and Tsatsakis, A and Ioannou, P},
title = {The Interplay Between Obesity and Type 2 Diabetes: Common Pathophysiological Mechanisms Contributing to Telomere Shortening.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
pmid = {40566527},
issn = {2075-1729},
abstract = {The worldwide prevalence of obesity continues to increase, representing a serious public health issue due to associated comorbidities. Obesity is associated with type 2 diabetes mellitus (T2D), which shares similar pathophysiological mechanisms. In both conditions, oxidative stress, inflammation, mitochondrial dysfunction, abnormal adipose tissue function, and senescence are observed, ultimately leading to insulin resistance. In both cases, hypertrophic adipose tissue is associated with telomere shortening. Elucidating the mechanisms underlying telomere shortening in obesity and diabetes may be crucial for deepening our understanding of these pathologies, with the ultimate aim of its translational implications. Several studies have shown that telomere shortening is present in patients with metabolic disorders, emphasizing its prognostic value for the onset and progression of these diseases. From this perspective, this article highlights the importance of telomere biology, which can aid in developing new therapeutic options for metabolic disorders.},
}

@article {pmid40563586,
year = {2025},
author = {Baliou, S and Pelagiadis, I and Apetroaei, MM and Vakonaki, E and Arsene, AL and Hatzidaki, E and Tzatzarakis, MN and Ioannou, P and Tsatsakis, A and Stiakaki, E},
title = {The Telomere Length Signature in Leukemias-From Molecular Mechanisms Underlying Telomere Shortening to Immunotherapeutic Options Against Telomerase.},
journal = {Cancers},
volume = {17},
number = {12},
pages = {},
doi = {10.3390/cancers17121936},
pmid = {40563586},
issn = {2072-6694},
abstract = {The nucleoprotein structures known as telomeres provide genomic integrity by protecting the ends of chromosomes. Tumorigenesis is associated with alterations in telomere function and stability. This narrative review provides evidence of the potential prognostic value of telomere length and telomerase in leukemias. On the one hand, oxidative stress and mitochondrial dysfunction can accelerate telomere shortening, leading to higher susceptibility and the progression of leukemia. On the other hand, cytogenetic alterations (such as gene fusions and chromosomal abnormalities) and genomic complexity can result from checkpoint dysregulation, the induction of the DNA damage response (DDR), and defective repair signaling at telomeres. This review thoroughly outlines the ways by which telomere dysfunction can play a key role in the development and progression of four primary leukemias, including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and acute leukemias of myeloid or lymphoid origin, highlighting the potential prognostic value of telomere length in this field. However, telomerase, which is highly active in leukemias, can prevent the rate of telomere attrition. In line with this, leukemia cells can proliferate, suggesting telomerase as a promising therapeutic target in leukemias. For this reason, telomerase-based immunotherapy is analyzed in the fight against leukemias, leveraging the immune system to eliminate leukemia cells with uncontrolled proliferation.},
}

@article {pmid40561208,
year = {2025},
author = {Catto, LFB and Aggarwal, N and Shalhoub, RN and Ma, X and Darden, I and Machado, T and Zhang, Y and Redekar, N and Thongon, N and Colla, S and Aubert, G and Dunbar, CE and Wu, CO and Young, NS and Patel, BA and Gutierrez-Rodrigues, F and Groarke, EM},
title = {Clinical and molecular features of immunodeficiency in patients with telomere biology disorders.},
journal = {Blood},
volume = {},
number = {},
pages = {},
doi = {10.1182/blood.2024026735},
pmid = {40561208},
issn = {1528-0020},
abstract = {Immunodeficiency in telomere biology disorders (TBDs) has been described in pediatric patients with severe phenotypes, but less characterized within the broader TBD spectrum. We collected complete blood counts, lymphocyte subsets, and infection history from 88 consecutive TBD patients with a median age of 37 years (range 6-76). Most patients were >18 years old (80/88; 90%) and harbored either a TERT (45%) or TERC (32%) germline mutation. Thirty-two patients (36%) experienced significant infections (opportunistic, recurrent, and/or requiring hospitalization); 47% had lymphopenia, and 3% severe neutropenia. Absolute lymphocyte counts (ALC) <0.96 and <1.1 x103/µL, but not severe neutropenia, associated with increased infection risk and lower overall survival, respectively. Decreased CD3+ T-cells, both CD4+ and CD8+, associated with BMF, increased infection risk, and reduced survival. Low CD3+ and CD4+ associated with solid cancers. Telomere length was shortened across the cohort without correlation with ALC or lymphocyte subsets. In a predominantly adult cohort of TBDs, immunodeficiency was marked by T lymphopenia, possibly a consequence of accelerated aging in the hematopoietic compartment. An ALC cut-off of <1.1 x103/µL may be a useful biomarker to identify patients with an increased risk of infection, a major cause of death of TBD patients.},
}

@article {pmid40561046,
year = {2025},
author = {Bae, CY and Kim, IH and Kim, SH and Chun, H and Kim, BS and Jeon, MH},
title = {Effects of lifestyle on telomere length: A study on the Korean population.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0325233},
pmid = {40561046},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; *Life Style ; Middle Aged ; Republic of Korea ; Adult ; *Telomere/genetics ; *Telomere Homeostasis ; Aged ; *Aging/genetics ; Exercise ; Sleep ; Alcohol Drinking ; Smoking ; },
abstract = {Telomere length is a known indicator of biological aging, typically decreasing with age. Biological age is a benchmark for assessing an individual's health and aging. Correlations between telomere length and lifestyle factors have primarily been investigated from the perspective of a single variable and predominantly examined in postmenopausal women in Korea. This study aimed to analyze the effects of multiple lifestyle factors on telomere length in a diverse Korean population comprising 368 healthy adults (174 men and 194 women). We measured anthropometric and blood-related parameters and collected data on lifestyle-related factors, such as exercise, smoking, alcohol consumption, sleep, and stress, using surveys. Telomere length was quantified using monochrome multiplex quantitative real-time polymerase chain reaction (qPCR), and the relationship between lifestyle factors and telomere length was analyzed using correlation and regression analyses (p-value <0.10). Our findings indicated that telomere age, derived from telomere length, significantly increased with each adverse lifestyle factor. For men, significant contributors included exercise, smoking, and stress, whereas for women, significant contributors were exercise, alcohol consumption, sleep, and stress. The results showed that lifestyle and biological age considerably affected telomere age and accelerated the aging process. These results emphasize the importance of lifestyle in the management of biological aging.},
}

Humans
Female
Male
*Life Style
Middle Aged
Republic of Korea
Adult
*Telomere/genetics
*Telomere Homeostasis
Aged
*Aging/genetics
Exercise
Sleep
Alcohol Drinking
Smoking

@article {pmid40560939,
year = {2025},
author = {Campbell, AM and Anderson, MG and Haussmann, MF and Rowell, R and Jacobs, L},
title = {Telomere length as a biomarker for cumulative experience in broiler chickens.},
journal = {PloS one},
volume = {20},
number = {6},
pages = {e0326195},
pmid = {40560939},
issn = {1932-6203},
mesh = {Animals ; *Chickens/genetics ; Male ; *Telomere/genetics/metabolism ; Biomarkers/metabolism ; *Telomere Homeostasis ; },
abstract = {Cumulative experience can be defined as the sum of all positive and negative experiences during an animal's lifetime. Telomere length shows promise as a biomarker of cumulative experience in humans and non-human animals but is not yet assessed for broiler chickens. Therefore, our objective was to determine telomere length changes due to positive and negative experiences in fast-growing broiler chickens. In three replicated experiments, male Ross 708 broilers were housed in a 2 × 2 factorial study investigating high environmental complexity as a positive environment (vs. low complexity; 6 pens/treatment) and high stocking density as a negative environment (vs. low density; 6 pens/treatment). Telomere length was quantified at day 48 of age via quantitative RT-PCR (qRT-PCR) from gonad and kidney samples (N = 9 samples/treatment/tissue/experiment). Prior to analysis, raw relative telomere length (rTL) values were z-transformed to allow comparison between experiments. Combined data from the three experiments were analyzed using mixed models with complexity, density, and their interactions as fixed factor and pen nested within experiment and qRT-PCR plate number as random factors. Over all three trials, birds housed in high complexity environments tended (P = 0.0503) to have longer telomeres from kidney tissue than birds housed in low complexity environments. Stocking density did not impact combined kidney telomere length and gonadal telomere length was not impacted by environmental complexity or stocking density. Longer telomeres (statistical trend) in response to positive experience (environmental complexity) when compared to low-complexity indicate that high-complexity environments elicited positive cumulative experience in broiler chickens, although effect size was small. Telomere length has the potential to be a valuable tool in the assessment of cumulative experience in production settings, and future works should replicate these findings and expand upon this work by comparing telomere length with other more traditional animal welfare markers.},
}

Animals
*Chickens/genetics
Male
*Telomere/genetics/metabolism
Biomarkers/metabolism
*Telomere Homeostasis

@article {pmid40560727,
year = {2025},
author = {Analikwu, BT and Deshayes, A and van der Torre, J and Guérin, TM and Katan, AJ and Béneut, C and Barth, R and Phipps, J and Scolari, V and Veaute, X and Busso, D and Dubrana, K and Mattarocci, S and Dekker, C and Marcand, S},
title = {Telomeres stall DNA loop extrusion by condensin.},
journal = {Cell reports},
volume = {44},
number = {7},
pages = {115900},
doi = {10.1016/j.celrep.2025.115900},
pmid = {40560727},
issn = {2211-1247},
abstract = {DNA loop extrusion by SMC proteins is a key process underlying chromosomal organization. It is unknown how loop extruders interact with telomeres where DNA is densely covered with proteins. Using complementary in vivo and in vitro single-molecule approaches, we study how loop-extruding condensin interacts with Rap1, the telomeric DNA-binding protein of Saccharomyces cerevisiae. We show that dense linear Rap1 arrays can completely halt DNA loop extrusion, with a blocking efficiency depending on the array length and the DNA gap size between proteins. In anaphase cells, dense Rap1 arrays are found to accumulate condensin and to cause a local chromatin decompaction, as monitored with a microscopy-based approach, with direct implications for the resolution of dicentric chromosomes produced by telomere fusions. Our findings show that linear arrays of DNA-bound proteins can efficiently halt DNA loop extrusion by SMC proteins, which may impact cellular processes from telomere functions to transcription and DNA repair.},
}

@article {pmid40558975,
year = {2025},
author = {Yang, Y and Huang, J and Dong, G and Hu, X},
title = {Telomere-to-Telomere Assembly of the Cordyceps militaris CH1 Genome and Integrated Transcriptomic and Metabolomic Analyses Provide New Insights into Cordycepin Biosynthesis Under Light Stress.},
journal = {Journal of fungi (Basel, Switzerland)},
volume = {11},
number = {6},
pages = {},
pmid = {40558975},
issn = {2309-608X},
support = {No. 2022EHB047//Program of Hubei Province for International Cooperation/ ; No.20232354C01//Amway (China) Daily-Use Commodity/ ; },
abstract = {Cordyceps militaris, a model species in the genus Cordyceps, is widely distributed globally and is known for its significant medicinal value. It has been traditionally used in Chinese medicine to enhance immunity, alleviate fatigue, and treat tumors, among other therapeutic purposes. Here, we successfully assembled a telomere-to-telomere (T2T) level genome of C. militaris CH1 using PacBio HiFi and Hi-C technologies. The assembled genome is 32.67 Mb in size, with an N50 of 4.70 Mb. Gene prediction revealed a total of 10,749 predicted genes in the C. militaris CH1 genome, with a gene completeness of 99.20%. Phylogenetic analysis showed the evolutionary relationship between C. militaris CH1 and other Cordyceps species, suggesting that the divergence between this strain and C. militaris ATCC 34164 occurred approximately 1.36 Mya. Combined transcriptomic and metabolomic analyses identified 842 differentially expressed genes and 2052 metabolites that were significantly altered under light stress, primarily involving key pathways related to amino acid metabolism, purine metabolism, and secondary metabolite biosynthesis. Joint analysis of genes and metabolites revealed 79 genes coding for enzymes associated with the synthesis of adenine and adenosine, with the expression of 52 genes being upregulated, consistent with the accumulation trends of adenine and adenosine. Four gene clusters related to the synthesis of cordycepin were identified, with a significant upregulation of cns3 (FUN_003263), suggesting that light stress may promote cordycepin biosynthesis. This comprehensive analysis not only provides new insights into the genomics, metabolomics, and functional gene research of C. militaris CH1 but also offers a potential biological foundation for understanding the synthesis mechanisms of cordycepin and its efficient production.},
}

@article {pmid40556866,
year = {2025},
author = {Vos, S and Martens, DS and De Waele, E and Dewyspelaere, G and Mistiaen, G and Goeminne, P and Nawrot, TS},
title = {Telomere length and COVID-19 disease severity: insights from hospitalized patients.},
journal = {Frontiers in aging},
volume = {6},
number = {},
pages = {1577788},
pmid = {40556866},
issn = {2673-6217},
abstract = {INTRODUCTION: Telomere length is associated with various disease and immune function and may therefore impact COVID-19 disease severity. We studied the associations between telomere length as a geroprotective susceptibility marker and clinical outcomes in hospitalized COVID-19 patients.

METHODS: 283 hospitalised COVID-19 patients (before vaccination, recruited between May 2020 and March 2021) were recruited for this cross-sectional study. Blood telomere length was determined by qPCR. The association between blood telomere length and clinical outcomes was examined using logistic regression, while adjusting for various covariates and confounders including demographic factors, comorbidity, body-mass index and blood cell counts. The primary clinical outcomes assessed were duration of stay, risk of ICU admission, and risk of requiring ventilation support.

RESULTS: Independent of sex and chronological age, an interquartile-range (IQR) increase in blood telomere length was associated with more favourable clinical outcomes in hospitalised COVID-19 patients: specifically, the odds ratio for ICU admission was 0.55 (95%CI: 0.32-0.88). Moreover, the odds ratio for the risk of ventilation was 0.52 (95%CI: 0.31-0.84). Finally, ordinal logistic regression revealed a lower odds for being in a higher quantile of hospital duration (OR: 0.79, 95%CI: 0.58-1.06).

DISCUSSION: To conclude, we found that in hospitalised COVID-19 patients, longer telomeres was associated with lower diseases severity in hospitalised COVID-19 patients, that could not be explained by shifts in blood cell counts. Therefore supporting the geroprotective or immunoprotective effects associated with longer telomeres conferring lower susceptibility to severe COVID-19 outcomes.},
}

@article {pmid40556056,
year = {2025},
author = {Talon, AF and Razia, D and Sum, J and Sista, R},
title = {EXPRESS: Narrative Review: Chronic Lung Allograft Dysfunction with Focus on Short Telomere Syndrome, Adjunctive Therapies, and MRI Detection.},
journal = {Journal of investigative medicine : the official publication of the American Federation for Clinical Research},
volume = {},
number = {},
pages = {10815589251355173},
doi = {10.1177/10815589251355173},
pmid = {40556056},
issn = {1708-8267},
abstract = {Lung transplantation (LTx) is a vital treatment option for patients with end-stage lung diseases, significantly enhancing survival rates and quality of life. Nonetheless, chronic lung allograft dysfunction (CLAD) remains the primary cause of long-term morbidity and mortality in LTx recipients, posing substantial challenges to patient outcomes and healthcare systems. Despite progress in surgical methods and immunosuppressive treatments, CLAD management is complicated by its multifaceted, potentially irreversible nature. This review delves into critical aspects such as short telomere syndrome (STS), innovations in early detection, and adjunctive therapeutic approaches, offering insights into strategies that may extend the survival of LTx recipients. STS exacerbates CLAD by accelerating cellular aging and hindering tissue repair, necessitating a multidisciplinary approach involving pulmonologists, geneticists, hepatologists, and hematologists to devise comprehensive care plans. The review emphasizes dynamic magnetic resonance imaging as a promising tool for early CLAD detection, enhancing patient monitoring capabilities. Additionally, it examines the roles of extracorporeal photopheresis (ECP), total lymphoid irradiation (TLI), and anti-thymocyte globulins as adjunctive therapies, advocating for their inclusion in standard treatment protocols. This could lead to broader adoption and insurance coverage. Furthermore, we attempt to provide a framework to help decide which adjunctive treatments should be pursued based on the available evidence. By assessing these strategies and highlighting the importance of personalized care, this review aims to guide future research and clinical practice, ultimately improving CLAD management in lung transplant recipients.},
}

@article {pmid40552812,
year = {2025},
author = {Hoyer, LL and Souza, CP and Hung, C-C and Hogan, EK and Hernandez, AG},
title = {A telomere-to-telomere genome assembly for Malassezia pachydermatis ATCC 14522 (CBS 1879).},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0012525},
doi = {10.1128/mra.00125-25},
pmid = {40552812},
issn = {2576-098X},
abstract = {Pacific Biosciences (PacBio) long-read sequencing was used to generate a telomere-to-telomere genome assembly for the Malassezia pachydermatis type strain ATCC 14522 (CBS 1879). The assembly included six chromosomes. The nuclear genome was 8.4 Mb, with a GC content of 55.3%, and 4,519 predicted genes.},
}

@article {pmid40552254,
year = {2025},
author = {Andreikos, DA and Spandidos, DA},
title = {Telomere length and skin cancer risk: A systematic review and meta-analysis of melanoma, basal cell carcinoma and squamous cell carcinoma.},
journal = {Oncology letters},
volume = {30},
number = {2},
pages = {395},
pmid = {40552254},
issn = {1792-1082},
abstract = {Skin cancer is one of the most prevalent types of cancer worldwide, with its global incidence rising despite prevention efforts. Telomere length (TL) has emerged as a potential biomarker for cancer risk; however, its relationship with skin cancer risk remains incompletely understood. To explore the association between TL and the risk of melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), a systematic review and meta-analysis was conducted. Longer TL was significantly associated with an increased risk in melanoma (pooled odds ratio: 0.51; 95% confidence interval: 0.38-0.69; P<0.0001). A significant association between longer TL and increased melanoma risk was identified in both familial melanoma and the general population. Subgroup analyses revealed consistent associations across sex, population source and adjustments for confounding factors. Geographic stratification indicated stronger associations in studies conducted in the USA compared with those from European populations. A meta-analysis of BCC and SCC studies did not achieve statistical significance, although qualitative synthesis suggested a potential association between shortened TL and increased risk. The significant association of longer TL and increased melanoma risk diverges from the conventional hypothesis that telomere shortening elevates cancer risk, highlighting a cancer-type specific telomeric relationship. The inconclusive findings for BCC and SCC underscore the necessity for further detailed investigation. Large-scale prospective studies with standardized methodologies are imperative to validate these findings and explore the underlying mechanisms. The present findings suggested that TL could potentially serve as a valuable biomarker for melanoma risk stratification in dermatologic oncology.},
}

@article {pmid40551485,
year = {2025},
author = {Wen, W and Chen, S and Coulter, K and Kim, SY},
title = {The association of depressive symptoms and telomere length among Mexican-origin youth: How it varies by family environment.},
journal = {Journal of research on adolescence : the official journal of the Society for Research on Adolescence},
volume = {35},
number = {2},
pages = {e70047},
pmid = {40551485},
issn = {1532-7795},
support = {1651128//National Science Foundation/ ; 0956123//National Science Foundation/ ; 1R21MD012706-01A1/MD/NIMHD NIH HHS/United States ; 3R21MD-012706-02S1/MD/NIMHD NIH HHS/United States ; 5R03HD060045-02//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 2P2CHD042849-21A1//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 2T32HD007081-46A1//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 2699//Russell Sage Foundation/ ; 10023427//Spencer Foundation/ ; JRG-102//Hogg Foundation for Mental Health/ ; //Office of the Vice President for Research and Creative Grant and Special Research Grant from the University of Texas at Austin/ ; //College of Natural Sciences Catalyst Grant from the University of Texas at Austin/ ; 1K99MD019319/MD/NIMHD NIH HHS/United States ; },
mesh = {Humans ; Female ; Adolescent ; Male ; *Depression/ethnology/psychology/genetics ; *Mexican Americans/psychology/statistics & numerical data ; *Telomere Shortening ; Child ; Parenting/psychology/ethnology ; *Emigrants and Immigrants/psychology ; *Telomere ; Socialization ; White ; },
abstract = {Telomere length is an important indicator of aging and related diseases. Identifying risk and protective factors for telomere shortening early in life among youth from Mexican immigrant families is critical for reducing ethnic health disparities. This study investigates how familial environmental factors (i.e., culture-general and culture-specific parenting and parentification experiences) shape individual differences in the association between depressive symptoms and telomere length. Adolescents from immigrant families (n = 325; Mwave1.age = 12.81) self-reported their perceptions of maternal hostility, warmth, cultural socialization, and parentification experiences across three waves during adolescence, as well as depressive symptoms in late adolescence (Mwave3.age = 17.61). Youth also provided dried blood spots for telomere length assessment at Wave 3. Moderation models were conducted in Mplus 8.3 with basic sociodemographic variables and BMI controlled. Maternal hostility, cultural socialization, and parentification during adolescence, but not maternal warmth, were critical family context factors impacting biological (i.e., telomere length) responses to depressive symptoms. Higher depressive symptoms were related to shorter telomere length in late adolescence only for youth who experienced high levels of maternal hostility, lower cultural socialization, or lower parentification experiences during adolescence. This study highlights the importance of cultivating cultural assets through culturally specific parenting and family experiences during adolescence, demonstrating their role in mitigating the link between depressive symptoms and accelerated cellular aging as shown by telomere length.},
}

Humans
Female
Adolescent
Male
*Depression/ethnology/psychology/genetics
*Mexican Americans/psychology/statistics & numerical data
*Telomere Shortening
Child
Parenting/psychology/ethnology
*Emigrants and Immigrants/psychology
*Telomere
Socialization
White

@article {pmid40550303,
year = {2025},
author = {Janet Chik, HY and Gillings, MM and Ton, R and van der Velde, M and Taylor, MP and Swaddle, JP and Dugdale, HL and Griffith, SC},
title = {Telomere length declines with mean blood lead concentration in an urban passerine.},
journal = {Environmental research},
volume = {},
number = {},
pages = {122210},
doi = {10.1016/j.envres.2025.122210},
pmid = {40550303},
issn = {1096-0953},
abstract = {Lead (Pb) is a highly toxic and widespread environmental pollutant and can severely harm body tissues as well as DNA. Pb could potentially damage telomeres, whose length and shortening rate are linked with cellular senescence, physiological state, and mortality. Yet, studies investigating Pb and telomere dynamics in natural systems remain inconclusive. In this study, we used a free-living house sparrow (Passer domesticus) population in Broken Hill, Australia, chronically exposed to varying levels of environmental Pb, to assess the effects of Pb on telomere length and telomere rate of change. Using all data from adults and juveniles, we found that mean blood Pb concentration had a negative relationship with telomere lengths measured at capture sites, such that a standard deviation increase in the concentration of blood Pb was associated with an 8% decrease in telomere length. In a series of robustness analyses we found that this negative relationship existed at both the individual and the site levels. Although not statistically significant, the relationship between telomere length and soil Pb also appeared to be consistent with that found for blood Pb. Our results demonstrated that while exposure to Pb damages telomeres in free-living house sparrows, the biological effect is relatively weak, and is only identified with a sample size of over 500 individuals. Nevertheless, our data reveal that in this urban setting in Australia, a human commensal bird is suffering from lead-induced damage to telomeres. Given the well-established relationship between telomere shortening and life-span, our study highlights a clear risk of Pb contamination on the biota of the urban area, including humans.},
}

@article {pmid40544370,
year = {2025},
author = {Martin, C and Ruthsatz, K and Gomez-Mestre, I and Burraco, P},
title = {Growth but Not Corticosterone, Oxidative Stress, or Telomere Length Is Negatively Affected by Microplastic Exposure in a Filter-Feeding Amphibian.},
journal = {Journal of experimental zoology. Part A, Ecological and integrative physiology},
volume = {},
number = {},
pages = {},
doi = {10.1002/jez.70005},
pmid = {40544370},
issn = {2471-5646},
support = {//The German Research Foundation (DFG) project (533973724); a new actor on the stage of global change: A multi-level perspective on the toxicity of microplastics pollution in amphibians) supported C.M. and K.R. Ramón y Cajal Fellowship RYC 2023-044964-I (Spanish Ministry of Science and Innovation) supported P.B./ ; },
abstract = {Microplastics (MPs) are of increasing global concern for species inhabiting aquatic habitats. However, the mechanisms behind animal responses to MPs still require comprehensive exploration. Amphibians are the most threatened vertebrate group with most species having a complex life cycle, commonly with an aquatic larval stage. Here, we investigated whether exposure to an environmentally relevant concentration of MPs affects the growth of filter-feeding larvae of the African clawed frog (Xenopus laevis), and the consequences for their stress physiology (corticosterone [CORT] levels), or health and ageing physiology (oxidative stress and telomere length, the latter in the liver and gut). We conducted a 3 × 2 experiment with three levels of fiber exposure (fibers absent -control-, and MP and cellulose fiber treatments), and two stress levels (CORT absent -control-, and CORT present simulating a stressful condition). We observed a negative impact of MP exposure on larval growth; however, this did not alter the CORT levels, oxidative stress. or telomere length. Our study shows that realistic concentrations of MPs are not enough to induce major alterations on the stress or health and ageing physiology of a filter-feeding amphibian. Whether compensatory growth responses during the post-metamorphic stages could lead to detrimental effects later in life should be explored in amphibians and other organisms with complex life cycles.},
}

@article {pmid40540389,
year = {2025},
author = {Huang, YC and Lu, HY and Zhang, L and Olivier, A and Wu, TL and Hsu, CY and LeGrand, C and Zeng, H and Curran, S and Wang, Q and Nannapaneni, R and Zhang, X and Ticó, M and Mariotti, M and Wu, RTY and Combs, GF and Cheng, WH},
title = {Dietary Selenium Deficiency Accelerates the Onset of Aging-Related Gut Microbial Changes in Aged Telomere-Humanized Mice, With Akkermansia muciniphila Being the Most Prominent and Alleviating Selenium Deficiency-Induced Type 2 Diabetes.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70130},
doi = {10.1111/acel.70130},
pmid = {40540389},
issn = {1474-9726},
support = {DK117407/NH/NIH HHS/United States ; 3062-51000-050-00D//Agricultural Research Service/ ; },
abstract = {Previous studies have shown that dietary selenium (Se) deficiency in mice reshapes gut microbiota, exacerbates healthspan deterioration (e.g., type 2 diabetes), and paradoxically activates beneficial longevity pathways. This study demonstrated that dietary Se deficiency accelerated many age-related gut microbial changes in aged telomere-humanized C57BL/6J diabetic mice in a sexually dimorphic manner, with Akkermansia muciniphila showing the greatest enrichment in males. However, dietary Se deficiency did not enrich A. muciniphila in mature or middle-aged male C57BL/6J wild-type mice. Oral gavage of A. muciniphila alleviated Se deficiency-induced type 2 diabetes-like symptoms, reversed mucosal barrier dysfunction and gut inflammation, and resulted in a trend of symbiotic and competitive suppression changes in certain gut bacteria in mature wild-type mice under conventional conditions. The beneficial effects of A. muciniphila appeared to be independent of selenoproteins sensitive to dietary Se deficiency, such as GPX1, SELENOH, and SELENOW, in the liver and muscle. Altogether, these results show that dietary Se deficiency accelerates age-related A. muciniphila enrichment specifically in aged male mice with severe insulin resistance and pancreatic senescence, indicating a potential hormetic response to Se deficiency through reshaped gut microbiota, which alleviates hyperglycemia and partially compensates for healthspan decline.},
}

@article {pmid40539277,
year = {2025},
author = {Sharma, A and Sowpati, DT},
title = {Analysis of tandem repeats in seven telomere-to-telomere primate genomes.},
journal = {Journal of genetics},
volume = {104},
number = {},
pages = {},
pmid = {40539277},
issn = {0973-7731},
mesh = {Animals ; *Telomere/genetics ; Humans ; *Primates/genetics ; *Tandem Repeat Sequences/genetics ; *Genome ; High-Throughput Nucleotide Sequencing ; Evolution, Molecular ; Y Chromosome/genetics ; },
abstract = {Tandem repeats (TRs) are highly polymorphic low complexity regions present in all the genomes. The length variation in TRs, particularly that of short TRs (STRs), is associated with several cellular functions such as gene expression and genome organization. In humans, an abnormal expansion of a few STR loci is linked to neurodegenerative diseases. Despite their importance, limitations and gaps in reference genomes prohibit the comprehensive analysis of TRs. Recent advances in high-throughput sequencing technologies have enabled the generation of gapless, telomere-to-telomere (T2T) genomes of humans and other ape species. Here, we report the TR landscape of seven primate T2T genomes, including humans. Our analysis indicates that TRs of 1-100 nucleotide (nt) motifs cover 3.5-6.9% of large primate genomes, with the highest density observed in gorilla (69 kb per Mbp). Large motif size TRs are prevalent and contribute abundantly to higher-order repeats. As an example, we describe a species-specific 32 nt A/T rich motif that contributes to subtelomeric repeats. Finally, we present the motif decomposition and substructure of pentameric repeats in Y chromosomes of six ape species. Our work illutrates the dynamics of TRs in large genomes, and showcases the utility of complete genomes for better understanding the role of low complexity sequences.},
}

Animals
*Telomere/genetics
Humans
*Primates/genetics
*Tandem Repeat Sequences/genetics
*Genome
High-Throughput Nucleotide Sequencing
Evolution, Molecular
Y Chromosome/genetics

@article {pmid40537010,
year = {2025},
author = {Zhang, Q and Xu, C and Fan, J and Lou, C and Chen, J and Zhang, J and Mo, J},
title = {Telomere length as a predictive marker for long-term cognitive function in a mouse model of subarachnoid hemorrhage.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-24-01150},
pmid = {40537010},
issn = {1673-5374},
abstract = {Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis. Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage. However, there is notable absence of biological markers to predict long-term prognosis in this patient population. Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage, this study postulates that telomere length, a recognized biomarker for aging, could be used as a prognostic indicator for subarachnoid hemorrhage. A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage. Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals. Concurrently, the relative telomere length was analyzed by quantitative polymerase chain reaction, which was performed using DNA extracted from ear notch and brain tissue after each assessment. Furthermore, proteomic analysis was employed to investigate differential protein expression in hippocampal tissue. Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time. There was a significant positive correlation between telomere length and neurological test scores, confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage. Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes, energy metabolism, and cellular signal transduction. This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice. Thus, telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.},
}

@article {pmid40536886,
year = {2025},
author = {Yadav, HK and Singh, N and Singh, B and Kaur, V and Sawant, SV},
title = {Telomere-to-telomere genome assembly of linseed (Linum usitatissimum L.) for functional genomics and accelerated genetic improvement.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70183},
pmid = {40536886},
issn = {1467-7652},
support = {//Department of Biotechnology, Ministry of Science and Technology, India/ ; },
abstract = {Linseed (Linum usitatissimum L.), a member of the Linaceae family, is a versatile crop valued for its oil, fibre, nutritional and medicinal applications. Recognized as a superfood, linseed is rich in omega-3 fatty acid (~55%), lignans, high-quality proteins, dietary fibre and bioactive secondary metabolites. Previously published genome assemblies of linseed are quite fragmented and non-contiguous. In this study, we present a telomere-to-telomere (T2T) chromosome-scale genome assembly of the Indian linseed variety T397 using advanced sequencing approaches. The assembly comprises ~595 Mb of genomic sequences, with a scaffold N50 of 32.86 Mb, spanning 15 chromosomes, including 29 telomeres and 15 centromeres. A total of 34 572 protein-encoding genes were predicted with an average length of 2980.7 bp and an average of 5.0 exons per gene. Gene family analysis determines a considerable number of unique genes in linseed and its close relationship with Manihot esculenta and Ricinus communis. The higher expression of oleosin and FAD3 genes in linseed highlights their roles in oil accumulation and enrichment for omega-3 fatty acid. The metabolites found in the seeds were enriched for the biosynthesis of unsaturated fatty acids. Various potential key structural genes and transcription factors that regulate oil metabolism especially unsaturated fatty acids biosynthesis has been identified. Overall, the present study provides the potential genomic resources for accelerated genetic studies and improvement of linseed.},
}

@article {pmid40533492,
year = {2025},
author = {Zhou, Y and Chen, C and Fang, D and Wang, C and Peng, Y and Wang, B and Zhang, M and You, Y and Liu, Y and Deng, G and Jian, J and Xu, D},
title = {Telomere-to-telomere genome assembly of Phoxinus lagowskii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1025},
pmid = {40533492},
issn = {2052-4463},
mesh = {*Telomere/genetics ; *Genome ; Animals ; DNA Transposable Elements ; *Cyprinidae/genetics ; },
abstract = {As an important economic and ecological fish, Amur minnow (Phoxinus lagowskii) plays a significant role in food products as well as evolutionary, ecological research. However, a high-quality chromosome-level genome of P. lagowskii is not currently available. In this study, we report a T2T (Telomere-to-telomere) genome for P. lagowskii with chromosome-level. The finally assembled genome size is 1.04 G, with a contig N50 of 41.7 Mb, comprising 25 chromosomes. The transposable elements constituted 512.40 Mb (49.22%) of the assembled P. lagowskii genome, with DNA transposons 25.02% being the predominant repeat type. A total of 2,4610 protein-coding genes were predicted in P. lagowskii genome, with 99.96% of these genes being functionally annotated. The identification of telomeres, BUSCO assessment, mapping coverage, and sequencing depth collectively demonstrated the high quality of the genome assembly. The T2T genomic information serves as an invaluable resource for studies in evolution, comparative genomics, fish breeding applications, and ecological research.},
}

*Telomere/genetics
*Genome
Animals
DNA Transposable Elements
*Cyprinidae/genetics

@article {pmid40531666,
year = {2025},
author = {Liu, F and Li, Y and Wang, G and Zhang, D and Yang, X and Zhou, C and Zhou, R and Liu, H},
title = {The telomere-to-telomere gapless genome of grass carp provides insights for genetic improvement.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf059},
pmid = {40531666},
issn = {2047-217X},
support = {2024B03J1082//Guangzhou Key R&D Program/ ; U23A20249//National Natural Science Foundation of China/ ; },
mesh = {*Carps/genetics ; Animals ; *Telomere/genetics ; *Genome ; Molecular Sequence Annotation ; Genomics/methods ; Centromere/genetics ; Chromosomes/genetics ; },
abstract = {BACKGROUND: The grass carp (Ctenopharyngodon idella) is a large herbivorous freshwater fish belonging to the Cyprinidae family. It is widely cultivated as a food source in China and is renowned as one of the Four Great Domestic Fishes. Despite its economic importance, the published genome assemblies of grass carp remain incomplete due to gaps, thereby hindering molecular research and genetic improvement.

RESULTS: In this study, we report the assembly of a telomere-to-telomere (T2T) gap-free genome of the grass carp with total length of 890,918,310 bp for 24 chromosomes without gaps, representing the highest completeness and assembly quality to date. Our assembly contains 27,446 protein-coding genes, and 93.04% of all were annotated with multiple databases, with 48 telomeres and 24 centromeres characterized. Gap-free reference genomes enable us to study the structure of centromeres and identify conserved centromere-specific satellite motifs for grass carp. Furthermore, we identified 108 gene-related gaps across 12 chromosomes and 38 structural variations across 17 chromosomes in this T2T assembly.

CONCLUSIONS: The validated gap-free genome provides invaluable resource for future genomic studies grass carp, offering new insights into its genetic architecture and evolutionary dynamics.},
}

*Carps/genetics
Animals
*Telomere/genetics
*Genome
Molecular Sequence Annotation
Genomics/methods
Centromere/genetics
Chromosomes/genetics

@article {pmid40531189,
year = {2025},
author = {Roy, S and Azzalin, CM},
title = {Reading the DNA of telomeres.},
journal = {eLife},
volume = {14},
number = {},
pages = {},
pmid = {40531189},
issn = {2050-084X},
mesh = {*Telomere/genetics/metabolism ; Humans ; *DNA Damage ; *DNA/metabolism/genetics ; Neoplasms/genetics ; },
abstract = {Experiments with tools designed to detect DNA damage reveal unique and conserved features of telomeres in cancer cells.},
}

*Telomere/genetics/metabolism
Humans
*DNA Damage
*DNA/metabolism/genetics
Neoplasms/genetics

@article {pmid40530773,
year = {2025},
author = {Zhou, J and Antinori, ME and Bellotti, G and Chalot, M and Puglisi, E},
title = {Telomere-to-telomere genome assembly of Talaromyces purpureogenus strain ISA502 isolated from maize rhizosphere.},
journal = {Microbiology resource announcements},
volume = {},
number = {},
pages = {e0012225},
doi = {10.1128/mra.00122-25},
pmid = {40530773},
issn = {2576-098X},
abstract = {We present a telomere-to-telomere genome assembly of Talaromyces purpureogenus strain ISA502, isolated from the maize rhizosphere. The 30.33 Mb genome, assembled using hybrid sequencing, comprises 8 chromosomes with 99% BUSCO completeness, offering improved resolution over existing fragmented genomes and advancing studies on its ecological and biotechnological significance.},
}

@article {pmid40530700,
year = {2025},
author = {Smoom, R and May, CL and Lichtental, D and Bar-Ness, K and Rangel, R and Khoury, J and Nachmani, D and Avrahami, D and Ahangari, F and Skordalakes, E and Kaminski, N and Kaestner, KH and Tzfati, Y},
title = {Separation of telomere protection from length regulation by two different point mutations at amino acid 492 of RTEL1.},
journal = {Nucleic acids research},
volume = {53},
number = {11},
pages = {},
doi = {10.1093/nar/gkaf507},
pmid = {40530700},
issn = {1362-4962},
support = {2071/18//Israel Science Foundation/ ; 1342/23//Israel Science Foundation/ ; 2166/24//Israel Science Foundation/ ; 1R01DK139049-01/DK/NIDDK NIH HHS/United States ; R01-CA249929/DK/NIDDK NIH HHS/United States ; U01-DK-134995/DK/NIDDK NIH HHS/United States ; R01-HL-127349/DK/NIDDK NIH HHS/United States ; R01-HL-141852/DK/NIDDK NIH HHS/United States ; //Israel-UK-Palestine GROWTH/ ; },
mesh = {Animals ; Mice ; *Point Mutation ; *Telomere/genetics/metabolism ; *DNA Helicases/genetics/metabolism ; *Telomere Homeostasis/genetics ; Humans ; Microcephaly/genetics/pathology ; DNA Damage ; Intellectual Disability/genetics/pathology ; Disease Models, Animal ; X-Linked Intellectual Disability/genetics/pathology ; Growth Disorders/genetics/pathology ; Dyskeratosis Congenita/genetics/pathology ; Limb Deformities, Congenital/genetics/pathology ; Hematopoiesis/genetics ; Lung/pathology ; Amino Acid Substitution ; Fetal Growth Retardation ; },
abstract = {RTEL1 is an essential DNA helicase that plays multiple roles in genome stability and telomere length regulation. The ultra-long telomeres of the house mouse hinder its utility as a model for telomere-related diseases. We have previously generated a mouse model with human-length telomeres, termed "Telomouse," by substituting methionine 492 of mouse Rtel1 to a lysine (Rtel1M492K). In humans, a methionine to isoleucine mutation at this position causes the fatal telomere biology disorder Hoyeraal-Hreidarsson syndrome (HHS). Here, we introduced the Rtel1M492I point mutation into the mouse genome, generating another mouse model, which we termed "HHS mouse." The HHS mouse telomeres are not as short as those of the Telomouse but nevertheless display higher levels of telomeric DNA damage, fragility, and recombination, associated with anaphase bridges and micronuclei. The HHS mouse also exhibits aberrant hematopoiesis and pre-fibrotic alterations in the lung. These observations indicate that the two mutations at the same codon separate critical functions of RTEL1: Rtel1M492K mainly reduces the telomere length setpoint, while Rtel1M492I predominantly disrupts telomere protection. The two mouse models enable dissecting the mechanistic roles of RTEL1 and the different contributions of short telomeres and DNA damage to telomere biology disorders and genomic instability.},
}

Animals
Mice
*Point Mutation
*Telomere/genetics/metabolism
*DNA Helicases/genetics/metabolism
*Telomere Homeostasis/genetics
Humans
Microcephaly/genetics/pathology
DNA Damage
Intellectual Disability/genetics/pathology
Disease Models, Animal
X-Linked Intellectual Disability/genetics/pathology
Growth Disorders/genetics/pathology
Dyskeratosis Congenita/genetics/pathology
Limb Deformities, Congenital/genetics/pathology
Hematopoiesis/genetics
Lung/pathology
Amino Acid Substitution
Fetal Growth Retardation

@article {pmid40527455,
year = {2025},
author = {Kletkiewicz, H and Kowalski, K and Kęsy, J and Trzeciak, P and Nowak, A and Jefimow, M and Przybylska-Piech, A},
title = {Unpredictable warm spells in winter increase blood cortisol level but lengthen telomeres in a seasonal rodent Phodopus sungorus.},
journal = {Proceedings. Biological sciences},
volume = {292},
number = {2049},
pages = {20250819},
doi = {10.1098/rspb.2025.0819},
pmid = {40527455},
issn = {1471-2954},
mesh = {Animals ; *Phodopus/physiology/blood/genetics ; Seasons ; *Hydrocortisone/blood ; Photoperiod ; Male ; *Telomere ; Stress, Physiological ; *Telomere Shortening ; Female ; },
abstract = {Global warming and the increased frequency of unpredictable weather events may disrupt the proper timing of seasonal adjustments of a phenotype. This may lead to the deterioration of the animal's condition and shorten its lifespan. We tested whether warm spells in winter affect the baseline and stress-induced cortisol level and leukocyte relative telomere length in two winter phenotypes of Siberian hamster, Phodopus sungorus, responding and non-responding to short photoperiod. We found that both phenotypes increased cortisol levels in winter and that warm spells augmented this response. Under stable cold conditions, non-responding individuals were more vulnerable to short-term stress than responding ones. However, telomere length increased, suggesting that animals have a high potential to cope with stress and prevent telomere shortening or that these two variables are not directly related. In responding individuals, the higher incidence of torpor also prevented telomeres shortening. These results indicate that both phenotypes, responding and non-responding to short photoperiod, can overcome the challenges posed by an unpredictably changing environment.},
}

Animals
*Phodopus/physiology/blood/genetics
Seasons
*Hydrocortisone/blood
Photoperiod
Male
*Telomere
Stress, Physiological
*Telomere Shortening
Female

@article {pmid40524536,
year = {2025},
author = {Duque, A and Lin, J and Jeliffe-Pawlowski, L and Coleman-Phox, K and Rand, L and Wojcicki, JM},
title = {Leukocyte telomere length and birth characteristics associated with obesity in infancy in a predominantly Latinx cohort.},
journal = {Pediatric obesity},
volume = {},
number = {},
pages = {e70034},
doi = {10.1111/ijpo.70034},
pmid = {40524536},
issn = {2047-6310},
support = {//Preterm Birth Inititiatve (PTBi)/ ; //Little Giraffe Foundation/ ; },
abstract = {BACKGROUND: Previous studies suggest that in utero exposures may impact future weight gain trajectories in infancy. Leukocyte telomere length (LTL) collected at birth may be an additional variable to test in models for childhood obesity as adult studies suggest that LTL may be predictive of metabolic disease.

METHODS: Using a primarily Latinx mother-child longitudinal cohort design, we assessed the relationship between newborn LTL measured via quantitative PCR and obesity at 12 months (WFA ≥ 95th percentile). Secondary outcomes included weight-for-age (WFA) Z scores at 12 months and covariates included birth anthropometrics and maternal prenatal health. Logistic and linear regression models were used to assess independent predictors for infant obesity and WFA Z scores.

RESULTS: We followed 302 children until 12 months including 65.89% with Latinx ethnicity and 4.97% had obesity at 12 months. Independent predictors of obesity at 12 months included higher birthweight Z scores (OR 2.24, 1.16, 5.05) and WFA Z scores at 6 months (OR 1.56, 1.19, 2.05). Longer LTL at birth and higher Apgar scores at 5 min were protective (OR 0.04, 95%CI 0.002, 0.79 and OR 0.30, 95%CI 0.13-0.72, respectively). LTL at birth was negatively associated with WFA Z scores at 12 months of age in multivariable models (Coeff = -0.58, 95%CI -1.05, -0.12).

CONCLUSIONS: LTL at birth may be a marker, in addition to birthweight, that can be used to assess an infant's risk for subsequent obesity. Future studies are needed to better assess and determine possible maternal exposures associated with shorter newborn LTL.},
}

@article {pmid40523014,
year = {2025},
author = {Kumawat, S and Shametov, A and Valeeva, LR and Ju, Y and Martinez, I and Logeswaran, D and Chen, H and Coughlan, JM and Chen, JJ and Yuan, YW and Sobel, JM and Koo, DH and Shakirov, EV and Choi, JY},
title = {Monkeyflower (Mimulus) uncovers the evolutionary basis of the eukaryote telomere sequence variation.},
journal = {PLoS genetics},
volume = {21},
number = {6},
pages = {e1011738},
pmid = {40523014},
issn = {1553-7404},
mesh = {*Telomere/genetics ; *Evolution, Molecular ; Telomerase/genetics ; Phylogeny ; RNA/genetics ; Genetic Variation ; In Situ Hybridization, Fluorescence ; Transcriptome ; Eukaryota/genetics ; },
abstract = {Telomeres are nucleoprotein complexes with crucial role of protecting chromosome ends. Because of its vital functions, components of the telomere, including its sequence, should be under strong evolutionary constraint. Yet across the tree of life there are numerous examples of telomere sequence variation and the evolutionary mechanism driving this diversification is unclear. Here, we studied the telomeres in Mimulus by investigating the noncoding telomerase RNA (TR), which is a core component of the telomere maintenance complex and determines the telomere sequence in eukaryotes. We conducted de novo transcriptomics and genome analysis of 18 species, and discovered Mimulus has evolved at least three different telomere sequences: (AAACCCT)n, (AAACCCG)n, and (AAACCG)n. We discovered several species with TR duplications, implying functional consequences that could influence telomere evolution. For instance, M. lewisii harbored two sequence-divergent TR paralogs while its sister species the paralog had pseudogenized. Nanopore-sequencing and fluorescence in situ hybridization indicated M. lewisii had a sequence heterogeneous telomere, and Telomeric Repeat Amplification Protocol combined with Terminal Restriction Fragment analysis confirmed the telomerase can use both TR paralogs for telomere synthesis. Interestingly in closely related species M. cardinalis, TR was also duplicated and both paralogs were expressed but its telomere consisted of a single telomere repeat. Evolutionary analysis indicated the TR paralogs arose from an ancient duplication, which also underlies the evolutionary origin of multiple Mimulus species with divergent telomere sequences. We propose sequence variation in eukaryotic telomeres arises from an evolutionary process involving TR duplication, sequence divergence, and loss of TR paralog.},
}

*Telomere/genetics
*Evolution, Molecular
Telomerase/genetics
Phylogeny
RNA/genetics
Genetic Variation
In Situ Hybridization, Fluorescence
Transcriptome
Eukaryota/genetics

@article {pmid40519641,
year = {2025},
author = {Zhang, H and Audry, J and Runge, KW},
title = {A Chromosome End Without Terminal Telomere Repeats is Stable for Multiple Cell Divisions.},
journal = {microPublication biology},
volume = {2025},
number = {},
pages = {},
pmid = {40519641},
issn = {2578-9430},
abstract = {We have formed new short telomeres in Schizosaccharomyces pombe using an inducible nuclease that cuts near telomere repeats in cells that lack, cannot recruit or cannot fully activate telomerase. Sequencing these new telomeres showed that cells can divide at least 4 times with ~30 bp of non-telomeric sequence at the chromosome end in cells lacking telomerase, which contrasts with current models for the roles of terminal single-stranded telomere repeats and the telomere proteins in telomere protection and replication. Cells that cannot recruit or activate telomerase had similar results, with additional terminal truncations or telomere repeat addition.},
}

@article {pmid40515885,
year = {2025},
author = {Jiang, Y and Liu, J and Pan, B and Yu, S and Hu, C and Li, Q and Cheng, H and Chen, L and Jiang, M and Xu, D and Wang, C and Yan, J},
title = {Prediction of lung adenocarcinoma prognosis and clinical treatment efficacy by telomere-associated gene risk model.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {1102},
pmid = {40515885},
issn = {2730-6011},
support = {ZYTS-80//Teaching reform project of Southwest Medical University/ ; Q20015//Youth Innovation Research Project of Sichuan Province in 2020/ ; },
abstract = {BACKGROUND: The most prevalent cause of cancer-related death in China and across the globe is lung adenocarcinoma (LUAD). Telomere shortening (TS) has been found to contribute to the development of LUAD. Therefore, our aim is to investigate the impact of telomere-related genes (TRGs) on immunotherapy and clinical prognosis prediction in LUAD.

MATERIALS AND METHODS: TRGs were obtained from TelNet, while RNA-seq and clinical information were retrieved from the GEO and TCGA databases. TelNet preserves a series of genes known to be engaged in telomere maintenance and also provides information on the type of telomere maintenance mechanism in which the gene is involved. Data pertinent to RNA sequencing and clinical parameters were accessed from two widely-accessed electronic repositories- the GEO and TCGA databases, respectively. We conducted univariate Cox regression analysis in order to recognize prognostic TRGs and employed multivariate Cox regression analysis to develop a risk model for these TRGs. The patients were stratified into high-risk and low-risk groups based on the first quartile of the risk score. The predictive ability and stability of the model were subsequently verified through Kaplan-Meier analysis, ROC curve, and C-index. We investigated the immune landscapes of different risk groups and predicted their responses to immunotherapy. Lastly, we evaluated the sensitivity of different groups to commonly used chemotherapeutic and targeted drugs through drug sensitivity analysis.

RESULTS: Univariate Cox analysis identified 12 prognostic TRGs, while a signature consisting of 4 prognostic TRGs was constructed through multivariate Cox analysis. Survival analysis indicated a significantly shorter survival time in the high-risk group. The predictive immunotherapy analysis suggested that patients in the high-risk group may have a more favorable response to immunotherapy. Finally, we identified 28 appropriate chemotherapeutic and 51 targeted drugs for different patient groups.

CONCLUSION: The study has successfully developed a prognostic model for LUAD prediction that takes into account TRGs and predicts both prognosis and response to immunotherapy.},
}

@article {pmid40502707,
year = {2025},
author = {Gong, Y and Wang, Y and Delgado-Peraza, F and Nogueras-Ortiz, C and Noren Hooten, N and Croteau, DL and Temre, M and Molnar, AE and Bodogai, M and Zou, A and Abdelmohsen, K and Zhu, W and Zhang, Y and Gorospe, M and Weng, NP and Evans, MK and Kapogiannis, D and Liu, Y},
title = {Telomere attrition alters extracellular vesicles conferring adverse impacts on neuronal viability and inflammatory response.},
journal = {iScience},
volume = {28},
number = {6},
pages = {112661},
pmid = {40502707},
issn = {2589-0042},
abstract = {Telomere shortening is a hallmark of aging associated with various diseases, yet its impact on extracellular vesicles (EVs) remains poorly understood. We investigated EV abundance, size, cargo content, and functional implications in a human aging cohort and the telomerase reverse transcriptase null (Tert [-/-]) mice. Human plasma EVs showed reduced telomeric DNA cargo with age. In generation 3 (G3) Tert [-/-]mice with shortened telomeres, we observed a significant reduction in plasma EV concentration and tissue-specific changes in EV levels and telomeric DNA content. Proteomic analysis revealed altered protein levels related to inflammation and lipid metabolism in plasma- and tissue-derived EVs. Functionally, EVs from G3 Tert [-/-]mice stimulated a pro-inflammatory response in bone marrow-derived macrophages and exhibited neurotoxic effects on primary cultured neurons. These findings highlight the intricate interplay between telomere shortening and EV biology, underscoring the potential of EVs as intercellular mediators, biomarkers, and therapeutic targets for conditions associated with telomere loss.},
}

@article {pmid40501906,
year = {2025},
author = {Spindler, J and Pandolfo, F and Koch, AE and Piccirillo, P and Bihler, J and Morgenstern, M and Buschbaum, S and Coon, J and Hänsel-Hertsch, R and Mehta, KPM and Panier, S},
title = {SLX4IP acts in parallel to FANCM to limit BLM-dependent replication stress at ALT telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.28.656696},
pmid = {40501906},
issn = {2692-8205},
abstract = {UNLABELLED: Alternative Lengthening of Telomeres (ALT) is a telomerase-independent telomere maintenance mechanism that enables cancer cells to gain unlimited replicative capacity. ALT relies on recombination-mediated telomere elongation and is promoted by telomeric replication stress. However, ALT requires strict regulation, as excessive replication stress or recombination are cytotoxic. Central to ALT is the RecQ helicase BLM, which regulates telomeric replication stress and promotes telomere recombination and DNA synthesis. Despite its key role in the ALT pathway, BLM must be tightly regulated to prevent deleterious outcomes. Here, we identify SLX4IP as a key suppressor of BLM-driven replication stress at ALT telomeres. Loss of SLX4IP in ALT-positive cells leads to BLM-dependent telomeric replication stress and impaired replication fork progression. Mechanistically, SLX4IP limits the unwinding of unligated Okazaki fragments by BLM on the lagging strand during telomere replication. This reduces the formation of toxic 5' DNA flaps and prevents hyperactivation of ATR signalling and deleterious recombination levels. We also uncover a synthetic lethal interaction between SLX4IP and FANCM, an ATPase/translocase that is a known regulator of BLM at telomeric replication forks in ALT cells. We demonstrate that SLX4IP and FANCM act in parallel to restrain BLM activity, thereby maintaining the balance of replication stress and recombination that is necessary for productive ALT. These findings reveal a vulnerability in ALT-positive cancers lacking SLX4IP and establish SLX4IP as a potential biomarker for therapeutic strategies targeting FANCM.

HIGHLIGHTS: SLX4IP depletion activates the replication stress response at ALT telomeresSLX4IP acts in parallel to FANCM to limit replication stress at ALT telomeresThe synthetic lethal interaction between SLX4IP and FANCM is dependent on BLMSLX4IP depletion causes BLM-dependent lagging-strand replication stress.},
}

@article {pmid40499086,
year = {2025},
author = {Kimball, TN and Prapiadou, S and Tack, RWP and Yong-Qiang Tan, B and Senff, JR and Kourkoulis, C and Singh, S and Rosand, J and Anderson, CD},
title = {Association of Leucocyte Telomere Length With Stroke, Dementia, and Late-Life Depression: The Role of Modifiable Risk Factors.},
journal = {Neurology},
volume = {105},
number = {1},
pages = {e213794},
pmid = {40499086},
issn = {1526-632X},
mesh = {Humans ; Female ; Male ; Risk Factors ; Middle Aged ; *Leukocytes ; *Stroke/epidemiology/genetics ; Aged ; *Dementia/epidemiology/genetics ; *Depression/genetics/epidemiology ; Mendelian Randomization Analysis ; *Telomere ; United Kingdom/epidemiology ; Incidence ; },
abstract = {BACKGROUND AND OBJECTIVES: Stroke, dementia, and late-life depression (LLD) are age-related brain diseases that pose significant public health challenges and costs. Leucocyte telomere length (LTL) is a biological aging marker influenced by both genetic and lifestyle factors. The aim of our study was to determine the association between LTL and these diseases. We further investigated whether modifying risk factors of age-related brain disease, as measured using the Brain Care Score (BCS), mitigates LTL associations.

METHODS: We analyzed participants from the UK Biobank with available LTL and risk factor information. We examined LTL's associations with stroke, dementia, and LLD, individually and as a composite outcome, using continuous measures and tertile stratification. Disease risks were evaluated through cumulative incidence curves, incidence rates per 1,000 person-years, and adjusted Cox models. Risk comparisons across LTL tertiles were stratified by risk factor profiles, with high BCS (≥15) indicating healthier lifestyle choices and low BCS (≤10) reflecting less optimal lifestyle choices. Mendelian randomization (MR) was used to test causal associations.

RESULTS: The study included 356,173 participants (median age 56 years; 53.69% female). Shorter LTL was consistently associated with higher incidence rates across all outcomes. Participants in the shortest LTL tertile had elevated risks of the composite outcome (hazard ratio [HR] 1.11; 95% CI 1.08-1.15), stroke (HR 1.08; 95% CI 1.02-1.15), dementia (HR 1.19; 95% CI 1.12-1.26), and LLD (HR 1.14; 95% CI 1.09-1.18). Individuals with both shorter LTL and lower BCS faced significantly increased risks of age-related brain diseases (HR 1.11; 95% CI 1.07-1.16) and individually for stroke (HR 1.10; 95% CI 1.02-1.19), dementia (HR 1.17; 95% CI 1.08-1.28), and LLD (HR 1.13; 95% CI 1.07-1.19). Conversely, individuals with higher BCS within the shortest LTL group did not show a significant increase in risk of any age-related brain diseases. MR analyses did not identify causal relationships between LTL and these outcomes.

DISCUSSION: Individuals with shorter LTL are at increased risk of stroke, dementia, and LLD. Improved modifiable risk factor profiles seem to mitigate the impact of LTL on these diseases. Future research should explore the effectiveness of lifestyle interventions in mitigating adverse biological aging effects on brain health.},
}

Humans
Female
Male
Risk Factors
Middle Aged
*Leukocytes
*Stroke/epidemiology/genetics
Aged
*Dementia/epidemiology/genetics
*Depression/genetics/epidemiology
Mendelian Randomization Analysis
*Telomere
United Kingdom/epidemiology
Incidence

@article {pmid40498073,
year = {2025},
author = {Couteau, F and Gagné, LM and Boulay, K and Rousseau, P and Carbonneau, M and McQuaid, M and Sharma, J and Sawchyn, C and Fernandez, E and Glatz, D and Rizk, R and Lalonde, ME and Mehrjoo, Y and Chu, TW and Moquin-Beaudry, G and Beauséjour, C and Sergeev, M and Costantino, S and Avizonis, D and Topisirovic, I and Jabado, N and Wurtele, H and Autexier, C and Mallette, FA},
title = {R-2-hydroxyglutarate-mediated inhibition of KDM4A compromises telomere integrity.},
journal = {Nucleic acids research},
volume = {53},
number = {11},
pages = {},
pmid = {40498073},
issn = {1362-4962},
support = {//Fondation de l'Hôpital Maisonneuve-Rosemont/ ; MOP-133442/CAPMC/CIHR/Canada ; GER-163050/CAPMC/CIHR/Canada ; MOP-133449/CAPMC/CIHR/Canada ; PJT-166130/CAPMC/CIHR/Canada ; RGPIN-2019-05082//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2017-05227//Natural Sciences and Engineering Research Council of Canada/ ; //Terry Fox New Investigator Award/ ; //Terry Fox New Frontiers Program Project/ ; //Leukemia Lymphoma Society/ ; 18198//Cancer Research Society/ ; 24032//Cancer Research Society/ ; //Canada Foundation of Innovation/ ; //Dr. John R. and Clara M. Fraser Memorial Trust/ ; 116128//Terry Fox Foundation/ ; //McGill University/ ; //Fonds de Recherche du Québec - Santé/ ; //Cole Foundation/ ; //CRC/ ; },
mesh = {Humans ; *Glutarates/pharmacology/metabolism ; Isocitrate Dehydrogenase/genetics/metabolism ; *Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors/metabolism/genetics ; *Telomere/metabolism/drug effects/genetics ; Cellular Senescence/drug effects/genetics ; Histones/metabolism ; Cell Line, Tumor ; Tumor Suppressor Protein p53/metabolism/genetics ; Mutation ; },
abstract = {Mutation, deletion, or silencing of genes encoding cellular metabolism factors occurs frequently in human malignancies. Neomorphic mutations in isocitrate dehydrogenases 1 and 2 (IDH1/2) promoting the production of R-2-hydroxyglutarate (R-2HG) instead of α-ketoglutarate (αKG) are recurrent in human brain cancers and constitute an early event in low-grade gliomagenesis. Due to its structural similarity with αKG, R-2HG acts as an inhibitor of αKG-dependent enzymes. These include the JUMONJI family of lysine demethylases, among which KDM4A is particularly sensitive to R-2HG-mediated inhibition. However, the precise molecular mechanism through which inhibition of αKG-dependent enzymes by R-2HG promotes gliomagenesis remains poorly understood. Here, we show that treatment with R-2HG induces cellular senescence in a p53-dependent manner. Furthermore, expression of mutated IDH1R132H or exposure to R-2HG, which leads to KDM4A inhibition, causes telomeric dysfunction. We demonstrate that KDM4A localizes to telomeric repeats and regulates abundance of H3K9(me3) at telomeres. We show that R-2HG caused reduced replication fork progression, and that depletion of SMARCAL1, a helicase involved in replication fork reversal, rescues telomeric defects caused by R-2HG or KDM4A depletion. These results establish a model whereby IDH1/2 mutations cause R-2HG-mediated inhibition of KDM4A, leading to telomeric DNA replication defects, telomere dysfunction, and associated genomic instability.},
}

Humans
*Glutarates/pharmacology/metabolism
Isocitrate Dehydrogenase/genetics/metabolism
*Jumonji Domain-Containing Histone Demethylases/antagonists & inhibitors/metabolism/genetics
*Telomere/metabolism/drug effects/genetics
Cellular Senescence/drug effects/genetics
Histones/metabolism
Cell Line, Tumor
Tumor Suppressor Protein p53/metabolism/genetics
Mutation

@article {pmid40492114,
year = {2025},
author = {Zhang, Y and Fan, J and Zhao, J and Zhu, H and Xia, Y and Xu, H},
title = {A telomere-associated molecular landscape reveals immunological, microbial, and therapeutic heterogeneity in colorectal cancer.},
journal = {Frontiers in molecular biosciences},
volume = {12},
number = {},
pages = {1615533},
pmid = {40492114},
issn = {2296-889X},
abstract = {BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignancies of the gastrointestinal tract and remains a leading cause of cancer-related mortality worldwide. Although telomere biology has been increasingly implicated in immune modulation and tumor progression, its clinical significance in CRC remains poorly understood.

METHODS: We developed a telomere score, termed TELscore, by integrating transcriptomic and intratumoral microbiome profiles from publicly available colorectal cancer (CRC) cohorts. To comprehensively characterize TELscore subgroups, we performed pathway enrichment analysis, tumor immune microenvironment (TIME) profiling, and microbiome niche assessment. Whole-slide histopathological images (WSIs) and immunohistochemical (IHC) staining were utilized to visualize immune features, including tertiary lymphoid structures (TLSs), across subgroups. Patients were stratified into high and low TELscore categories, and the predictive robustness was validated across multiple independent training and validation cohorts. Chemotherapeutic drug sensitivity was evaluated using pharmacogenomic data from the Genomics of Drug Sensitivity in Cancer (GDSC) database. Furthermore, the predictive capacity of TELscore for immunotherapy response was independently assessed in an external cohort. Finally, single-cell RNA sequencing (scRNA-seq) analysis was conducted to further dissect the cellular landscape and immunological heterogeneity within the TME.

RESULTS: TELscore stratified patients into two biologically and clinically distinct subgroups. The high TELscore group, which exhibited significantly shorter DFS, showed marked enrichment of tumorigenic pathways such as EMT, along with a distinctly immunosuppressive TME. This was reflected by elevated ESTIMATE/TIDE scores and corroborated by CIBERSORT, which revealed increased infiltration of M0 macrophages and upregulation of immunosuppressive signatures. In contrast, the low TELscore group was enriched for cell cycle related pathways, including E2F targets and the G2/M checkpoint, and demonstrated higher infiltration of pro-inflammatory M1 macrophages. 16S rRNA sequencing further revealed a divergent intratumoral microbiome between subgroups, the high TELscore group harbored significantly greater relative abundance of Selenomonas and Lachnoclostridium, two pathogenic genera previously associated with colorectal tumorigenesis. Complementary histopathological assessment via WSI demonstrated a marked absence of intraTLSs in high TELscore tumors. From a therapeutic standpoint, high TELscore tumors exhibited reduced sensitivity to standard chemotherapeutic agents-including Fluorouracil, Irinotecan, Oxaliplatin, and Docetaxel-as reflected by elevated IC50 values. Conversely, these tumors demonstrated increased susceptibility to MAPK pathway inhibitors, such as Selumetinib and Trametinib. Notably, TELscore also served as a robust predictor of immunotherapy response, which was validated in the IMvigor210 cohort. Finally, scRNA analysis highlighted profound cellular and functional divergence between TELscore subgroups. We identified intensified intercellular communication between inflammatory macrophages and fibroblasts, reinforcing the presence of an immunosuppressive niche.

CONCLUSION: TELscore is a robust stratification tool that captures the interplay between tumor biology, immune characteristics, and microbial ecology in colorectal cancer. By identifying clinically relevant subtypes with distinct therapeutic vulnerabilities, TELscore offers a powerful framework to advance personalized treatment and precision oncology.},
}

@article {pmid40487781,
year = {2025},
author = {Mondolin, V and Karlsson, H and Perasto, L and Paunio, T and Vitikainen, E and Martens, DS and Karlsson, L and Tuulari, JJ and Kataja, EL},
title = {Associations of Leukocyte Telomere Length With Trait Resilience, Adverse Childhood Experiences, and Psychological Distress Among Expecting Parents in the FinnBrain Birth Cohort.},
journal = {Biological psychiatry global open science},
volume = {5},
number = {4},
pages = {100498},
pmid = {40487781},
issn = {2667-1743},
abstract = {BACKGROUND: Telomere attrition has previously been associated with mental health problems and adverse childhood experiences (ACEs). Resilience has been shown to protect against mental health problems even in the context of ACEs. In this study, we examined the associations between leukocyte telomere length (LTL), symptoms of psychological distress, ACEs, and trait resilience. We examined whether LTL mediates the negative effects of ACEs and whether trait resilience moderates the association between LTL and distress.

METHODS: The study population was drawn from the ongoing FinnBrain Birth Cohort Study and included 342 mothers and 339 fathers who had provided blood samples and questionnaire data during pregnancy. Questionnaire data included the Connor-Davidson Resilience Scale 10, Edinburgh Postnatal Depression Scale, Symptom Checklist-90, and Trauma and Distress Scale. Data analysis included regression analysis, mixed-methods models, and statistical evaluation.

RESULTS: ACEs were associated with depressive and anxiety symptoms. However, contrary to the initial hypothesis, LTL was not associated with ACEs or distress symptoms and thus did not mediate their association. Furthermore, resilience was not associated with LTL and did not moderate the possible association between LTL and distress symptoms.

CONCLUSIONS: We found no association between TL and ACEs, psychological distress, or trait resilience. The mild distress symptoms, limited exposure to high ACEs, and the predominantly moderate to high socioeconomic status in the sample may be relevant to interpreting these findings. Encouragingly, not all ACEs necessarily lead to telomere attrition.},
}

@article {pmid40484928,
year = {2025},
author = {Bai, J and Wang, M and Luo, Y and Duan, B and Yang, Y and Fu, Y and Li, S and Yang, Z and Zheng, P and Yu, T and Yin, X and Bai, H and Long, Q and Ma, Y},
title = {Tumor microenvironment remodeling with a telomere-targeting agent and its cooperative antitumor effects with a nanovaccine.},
journal = {Journal of nanobiotechnology},
volume = {23},
number = {1},
pages = {429},
pmid = {40484928},
issn = {1477-3155},
support = {82203034//National Natural Science Foundation of China/ ; 82073371//National Natural Science Foundation of China/ ; 202201AT070238//Science and Technology Project of Yunnan Province/ ; 2021-I2M-1-043//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/ ; 202401BC070009//Major Project in Basic Research of Yunnan Province/ ; 202002AA100009//Yunnan Province Major Science and Technology Special Project/ ; },
mesh = {Animals ; *Tumor Microenvironment/drug effects ; Mice ; *Cancer Vaccines/pharmacology ; *Telomere/drug effects/metabolism ; Cell Line, Tumor ; Humans ; *Antineoplastic Agents/pharmacology ; Female ; Mice, Inbred BALB C ; Immunogenic Cell Death/drug effects ; Cell Proliferation/drug effects ; Nanoparticles/chemistry ; Myeloid-Derived Suppressor Cells/drug effects ; Nanovaccines ; },
abstract = {The nucleoside analogue 6-thio-2'-deoxyguanosine (6-thio-dG, also known as THIO) is a telomere-targeting agent with important clinical potency. It can selectively kill telomerase-positive tumor cells. We previously reported that THIO could successfully induce immunogenic cell death (ICD) in multiple mouse tumor cell lines. In this study, we further explored the potential impact of THIO on remodeling the tumor microenvironment, regulating anti-tumor immune responses, and its possible synergistic effects with other therapeutic methods, such as tumor vaccines. Our results showed that THIO could also induce ICD in various human tumor cell lines. The induction of ICD in tumor cells promoted the migration and maturation of antigen-presenting cells. Administration of THIO significantly inhibited the growth of established CT26 and TC-1 tumors in mice. Meanwhile, it enhanced the anti-tumor CTL response and reduced the levels of immunosuppressive myeloid-derived suppressor cells (MDSCs) in both the spleen and tumor tissues. Additionally, THIO had a direct inhibitory effect on the proliferation and differentiation of MDSCs. Moreover, when combined with bacterial biomimetic vesicles or a nanovaccine, such as THIO with BBV or different Q11-tumor antigen peptide nanofibers, it exhibited enhanced anti-tumor effects and immune responses compared to monotherapy in either "immune hot" TC-1 tumors or "immune cold" B16-F10 tumors. In summary, THIO has the ability to remodel the tumor microenvironment, exert a specific killing effect on tumor cells, and effectively cooperate with tumor vaccines. This broadens the anti-tumor mechanisms of THIO and provides a promising strategy for improving anti-tumor immunotherapies.},
}

Animals
*Tumor Microenvironment/drug effects
Mice
*Cancer Vaccines/pharmacology
*Telomere/drug effects/metabolism
Cell Line, Tumor
Humans
*Antineoplastic Agents/pharmacology
Female
Mice, Inbred BALB C
Immunogenic Cell Death/drug effects
Cell Proliferation/drug effects
Nanoparticles/chemistry
Myeloid-Derived Suppressor Cells/drug effects
Nanovaccines

@article {pmid40483557,
year = {2025},
author = {She, H and Liu, Z and Xu, Z and Zhang, H and Wu, J and Cheng, F and Wang, X and Qian, W},
title = {A complete telomere-to-telomere assembly of Spinacia oleracea genome reveals Y chromosome evolution and centromere landscape.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101410},
doi = {10.1016/j.xplc.2025.101410},
pmid = {40483557},
issn = {2590-3462},
}

@article {pmid40481860,
year = {2025},
author = {de Mendonça Nunes, B and Nunes de Oliveira, MB and da Silva Dantas, FJ and de Souza da Fonseca, A},
title = {Low-power red laser and ultraviolet A LED irradiation reduces mRNA levels from telomere maintenance genes in Saccharomyces cerevisiae.},
journal = {Lasers in medical science},
volume = {40},
number = {1},
pages = {260},
pmid = {40481860},
issn = {1435-604X},
mesh = {*Saccharomyces cerevisiae/radiation effects/genetics ; *RNA, Messenger/metabolism/genetics ; *Low-Level Light Therapy ; *Ultraviolet Rays ; *Telomere/radiation effects/genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; },
abstract = {Therapeutic protocols based on photobiomodulation (PBM) have been used for treatment of clinical conditions, such as wounds, pain, and inflammation processes. Existent data indicates that PBM is capable of altering reactive oxygen species (ROS) production. High levels of ROS can cause shortening and dysfunctional telomeres. Therefore, a better understanding of the effects induced by PBM on telomere maintenance is needed. This study aimed to assess the expression of genes related to telomere maintenance in Saccharomyces cerevisiae after irradiation with low-power red laser and ultraviolet A LED. Cultures of S. cerevisiae were exposed to low-power red laser (660 nm, 21.2 J/cm[2], 205 s, 99 mW) and ultraviolet A LED (390 nm, 6 J/cm[2], 205 s, 7 mW), incubated for 1 h in rich medium, total mRNA was extracted, cDNA was synthetized, and RAP1, RIF1, RIF2, STN1 and TEN1 mRNA levels in S. cerevisiae FF18733 cells were evaluated by real-time quantitative polymerase chain reaction. The results indicated that, at the fluences evaluated, exposure to low-power red laser does not induce changes on genes expression but exposure to ultraviolet A LED alone, and to simultaneous ultraviolet A LED and low-power red laser significantly (p < 0.05) reduce STN1 and TEN1 mRNA levels in S. cerevisiae. Exposure to low-power red laser could not affect mRNA telomere maintenance genes but exposure to ultraviolet A LED, and simultaneous low-power red laser and ultraviolet A LED, could decrease gene expression of telomere maintenance genes in S. cerevisiae. Our results could be taken into account for irradiation conditions carried out in current clinical protocols based on low-power lasers and LEDs as well as for developing new clinical protocols targeting telomere maintenance involved in PBM-induced therapeutic effects.},
}

*Saccharomyces cerevisiae/radiation effects/genetics
*RNA, Messenger/metabolism/genetics
*Low-Level Light Therapy
*Ultraviolet Rays
*Telomere/radiation effects/genetics
Saccharomyces cerevisiae Proteins/genetics/metabolism

@article {pmid40481055,
year = {2025},
author = {Han, JN and Li, Y and Li, W and Yan, HH and Yuan, F and Chen, HG and Han, DJ and Kang, ZS and Zeng, QD},
title = {Haplotype-resolved telomere-to-telomere genome assembly of the dikaryotic fungus pathogen Rhizoctonia cerealis.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {951},
pmid = {40481055},
issn = {2052-4463},
mesh = {Haplotypes ; *Telomere/genetics ; *Genome, Fungal ; *Rhizoctonia/genetics ; },
abstract = {Rhizoctonia cerealis, the causal agent of sharp eyespot, is a highly destructive pathogen of wheat. Despite its global importance, the genetic and molecular mechanisms underlying virulence of R. cerealis remain poorly understood. R. cerealis is a dikaryotic organism and the haplotype phase has been isolated. Based on the PacBio HiFi, Oxford Nanopore, and Hi-C platforms, we assembled the first high quality telomere-to-telomere (T2T) haplotype-resolved genome of R. cerealis, with sizes of 41.50 and 41.05 Mb, and N50 sizes of 2.67 and 2.42 Mb, respectively. High consensus quality values of 57.75 and 57.09 for the two haplotypes validated the accuracy of the assembly. The assembly achieved R-AQI and S-AQI scores of 92.5 and 100, respectively, both indicating reference-level quality. A total 25,353 protein coding genes were predicted for the two haplotypes with a BUSCO score of 96.7%. The genome assembly will serve as the foundation for further research on allele-specific expression, genetic variation and evolution of R. cerealis.},
}

Haplotypes
*Telomere/genetics
*Genome, Fungal
*Rhizoctonia/genetics

@article {pmid40480910,
year = {2025},
author = {Marston, K and Lau, CE and Andrusaityte, S and Bhopal, S and Grazuleviciene, R and Gutzkow, KB and Haro, N and Karachaliou, M and Koutra, K and Krog, NH and Lepeule, J and Maitre, L and Martens, DS and Pozo, OJ and Wijnhoven, A and Nawrot, TS and Vrijheid, M and Robinson, O},
title = {Associations of family affluence with cortisol production and telomere length in European children.},
journal = {EBioMedicine},
volume = {},
number = {},
pages = {105793},
doi = {10.1016/j.ebiom.2025.105793},
pmid = {40480910},
issn = {2352-3964},
abstract = {BACKGROUND: Shorter telomere length is associated with environmental stressors and has been proposed to underlie health inequalities in ageing trajectories. However, the relationship between socioeconomic position, psychosocial stress and telomere length is understudied in childhood, when ageing trajectories may be first defined. We aimed to examine the associations between family affluence, cortisol production and telomere length in a large cross-sectional study of European children.

METHODS: 1160 children, aged 5-12 years, participating in the Human Early Life Exposome (HELIX) project, were recruited from cohorts in the UK, France, Spain, Norway, Lithuania, and Greece. Family material wealth was assessed using the international family affluence scale (FAS), psychosocial stress was defined by total urinary cortisol production, and leucocyte telomere length was measured through qPCR. Associations of FAS with cortisol production and telomere length were analysed using sequentially adjusted multivariable linear regression. The mediating role of cortisol production in the association between FAS and telomere length was examined using natural effects models.

FINDINGS: Compared to children of low FAS, children with high FAS had 4.94% (95% CI: 1.2%, 8.8%) longer telomeres after adjustment for sex, age, ethnicity and cohort. Estimates were similar upon further adjustment for perinatal, child health, and other socioeconomic factors. Additionally, children of medium and high FAS had significantly lower levels of cortisol production than children of low FAS (medium FAS: -20.8%, 95% CI: -31%, -8.5%; high FAS: -16.6% SD, 95% CI: -28%, -3.4%). However, cortisol production was not associated with telomere length, and no significant mediation of cortisol production and other tested mediators was found for the relationship between FAS and telomere length.

INTERPRETATION: The impacts of economic disadvantage are biologically observable in children and have implications for understanding health inequalities, both in child development and the onset of later age-related disease. Given the lack of mediation by cortisol production levels, as assessed via spot urine samples, further research should investigate alternative mechanisms underlying the association between affluence and telomere length.

FUNDING: UK Research and Innovation (Grants: MR/S03532X/1, MR/Y02012X/1), European Community (Grants: 874583, 308333).},
}

@article {pmid40475990,
year = {2025},
author = {Wang, L and Pan, R and Yan, N and Luo, Y and Wang, Y},
title = {Association of self-reported sleep duration with leukocyte telomere length in type 2 diabetes mellitus patients.},
journal = {Frontiers in endocrinology},
volume = {16},
number = {},
pages = {1549175},
pmid = {40475990},
issn = {1664-2392},
mesh = {Humans ; *Diabetes Mellitus, Type 2/genetics/physiopathology ; Male ; Female ; *Leukocytes/metabolism ; Middle Aged ; Cross-Sectional Studies ; *Sleep/physiology ; Self Report ; Aged ; *Telomere/genetics ; China/epidemiology ; *Telomere Homeostasis ; Adult ; Sleep Duration ; },
abstract = {BACKGROUND: Leukocyte telomere length (LTL) is a biomarker of aging, and sleep duration is associated with LTL. However, research exploring the relationship between sleep duration and LTL has yielded inconsistent results. This study aimed to investigate the association between sleep duration and LTL in Chinese patients with type 2 diabetes mellitus (T2DM).

METHODS: A cross-sectional study involving 1,027 T2DM patients was conducted in Ningxia Province, China. Sleep duration was assessed through self-reported measures, while leukocyte telomere length (LTL) was determined using a quantitative polymerase chain reaction (q-PCR) method. Restricted cubic splines (RCS) analysis was initially performed to evaluate the potential nonlinear relationship between sleep duration and LTL. Subsequently, a multiple mixed-effect linear regression model was utilized to examine this association.

RESULTS: Binary analysis revealed an inverse association between sleep duration and LTL (β=-0.170, 95%CI: (-0.271, -0.068), p=0.001), indicating that for every 1-hour increase in sleep duration, LTL decreased by 0.17 kb. RCS analysis showed no evidence of a nonlinear relationship between sleep duration and LTL. After controlling for potential covariates, sleep duration remained negatively associated with LTL (β=-0.123, 95% CI: (-0.229, -0.017), p=0.022). When stratified by sleep quality (moderate or good vs. poor) and age (< 60 vs.≥60 years old), a negative association between sleep duration and LTL was particularly observed among individuals with moderate or good sleep quality and who were under 60 years old.

CONCLUSION: This study adds to the growing literature relating sleep duration with biomarkers of aging and suggests that the shortening of LTL may reflect potential mechanisms through which longer sleep duration contributes to pathological conditions in T2DM patients. It is recommended that healthcare providers, health promoters, and patients pay greater attention to sleep habits, avoiding excessively long sleep durations, to potentially slow cellular aging.},
}

Humans
*Diabetes Mellitus, Type 2/genetics/physiopathology
Male
Female
*Leukocytes/metabolism
Middle Aged
Cross-Sectional Studies
*Sleep/physiology
Self Report
Aged
*Telomere/genetics
China/epidemiology
*Telomere Homeostasis
Adult
Sleep Duration

@article {pmid40475761,
year = {2025},
author = {Feng, L and Bai, K and He, L and Wang, H and Zhang, W},
title = {Transcriptomic insights into the mechanism of action of telomere-related biomarkers in rheumatoid arthritis.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1585895},
pmid = {40475761},
issn = {1664-3224},
mesh = {Humans ; *Arthritis, Rheumatoid/genetics/diagnosis/immunology/metabolism ; Biomarkers/metabolism ; *Transcriptome ; *Telomere/genetics/metabolism ; Gene Expression Profiling ; Computational Biology/methods ; Gene Regulatory Networks ; Nomograms ; },
abstract = {BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease. The mechanism by which telomeres are involved in the development of RA remains unclear. This study aimed to investigate the relationship between RA and telomeres.

METHODS: In this study, we identified differentially expressed genes (DEGs) between RA and control samples by analyzing transcriptome data from a public database. Candidate genes were determined through the intersection of DEGs and telomere-related genes. Biomarkers were subsequently identified using machine learning algorithms, receiver operating characteristic analysis, and expression level comparisons between RA and control samples. Additionally, a nomogram model was employed to predict the diagnostic ability of biomarkers for RA. Subsequently, the potential mechanisms of these biomarkers in RA were further explored using gene set enrichment analysis (GSEA), subcellular localization, chromosome localization, immune infiltration, functional analysis, molecular regulatory networks, drug prediction, and molecular docking. Furthermore, the expression of biomarkers between RA and control samples was validated through in vitro experiments.

RESULTS: ABCC4, S100A8, VAMP2, PIM2, and ISG20 were identified as biomarkers. These biomarkers demonstrated excellent diagnostic ability for RA through a nomogram. Most of the biomarkers were found to be enriched in processes related to allograft rejection and the cell cycle. Subcellular and chromosomal localization analyses indicated that ABCC4 is localized to the plasma membrane, ISG20 to the mitochondria, PIM2 and S100A8 to the cytoplasm, and VAMP2 to the nucleus. Additionally, nine differential immune cells were identified between RA and control samples, with a strong correlation observed between the biomarkers and activated CD4 memory T cells. S100A8, PIM2, and VAMP2 exhibited high similarity to other biomarkers. Furthermore, three transcription factors (TFs), 121 microRNAs (miRNAs), and six long non-coding RNAs (lncRNAs) were identified as targeted biomarkers. Five drugs-methotrexate, adefovir, furosemide, azathioprine, and cefmetazole-were also identified as targeted biomarkers. Notably, ABCC4 interacted with all five drugs and exhibited the strongest binding energy with methotrexate. The results of the in vitro experiments were consistent with those obtained from the bioinformatics analysis.

CONCLUSION: This study identified five biomarkers-ABCC4, S100A8, VAMP2, PIM2, and ISG20-and offered new insights into potential therapeutic strategies for RA.},
}

Humans
*Arthritis, Rheumatoid/genetics/diagnosis/immunology/metabolism
Biomarkers/metabolism
*Transcriptome
*Telomere/genetics/metabolism
Gene Expression Profiling
Computational Biology/methods
Gene Regulatory Networks
Nomograms

@article {pmid40475582,
year = {2025},
author = {Ragupathi, A and Abid, HZ and Chen, Y and Zhao, R and Kosiyatrakul, ST and Yetil, DI and Neiswander, J and Feltman, R and Thomas, S and Yusupov, B and Singh, M and Zheng, L and Shen, B and Zhang, H and Chu, HC and Schildkraut, CL and Xiao, M and Zhang, D},
title = {DNA2 and FANCM function in two distinctive pathways in disrupting TERRA R-loops and suppressing replication stress at ALT telomeres.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.22.655602},
pmid = {40475582},
issn = {2692-8205},
abstract = {Cancers maintain their telomeres through two main telomere maintenance mechanisms (TMMs): 85-90% of cancers rely on telomerase, while 10-15% of cancers adopt the Alternative Lengthening of Telomere (ALT) pathway. Previously, we and others reported that FANCM, one of the Fanconi Anemia proteins, plays a critical role in suppressing replication stress and DNA damage at ALT telomeres by actively disrupting TERRA R-loops [1-4]. Here, we showed that inactivation of DNA2 in ALT-positive (ALT+) cells, but not in telomerase-positive (TEL+) cells, induces a robust increase of replication stress and DNA damage at telomeres, which leads to a pronounced increase of many ALT properties, including telomere dysfunction-induced foci (TIFs), ALT-associated PML bodies (APBs), and C-circles. We further demonstrated that depletion of DNA2 induces a pronounced increase of TERRA R-loops and a decrease in replication efficiency at ALT telomeres. Most importantly, we uncovered a strong additive genetic interaction between DNA2 and FANCM in the ALT pathway. Furthermore, co-depletion of DNA2 and FANCM causes synthetic lethality in ALT+ cells, but not in TEL+ cells, suggesting that targeting DNA2 and FANCM could be a viable strategy to treat ALT+ cancers. Finally, utilizing the single-molecule telomere assay via optical mapping (SMTA-OM) technology, we thoroughly characterized genome-wide changes in DNA2 deficient cells and FANCM deficient cells and found that most chromosome arms manifested increased telomere length. Unexpectedly, we uncovered many chromosome arm-specific telomere changes in those cells, suggesting that telomeres at different chromosome arms may regulate and respond to replication stress differently. Collectively, our study not only shed new light on the molecular mechanisms of the ALT pathway, but also discovered a new strategy for targeting ALT+ cancer.},
}

@article {pmid40469570,
year = {2025},
author = {Guzonjić, A and Jovanović, D and Simić, I and Ćeriman Krstić, V and Samardzić, N and Ostanek, B and Marc, J and Sopić, M and Kotur Stevuljević, J},
title = {Telomere length and oxidative stress in small cell lung cancer patients: changes through chemotherapy cycles compared to healthy controls.},
journal = {Biochemia medica},
volume = {35},
number = {2},
pages = {020705},
pmid = {40469570},
issn = {1846-7482},
mesh = {Humans ; Male ; Female ; *Oxidative Stress/drug effects ; *Lung Neoplasms/drug therapy/genetics/metabolism/mortality ; *Small Cell Lung Carcinoma/drug therapy/genetics/metabolism/mortality ; Middle Aged ; Aged ; Aryldialkylphosphatase/metabolism ; *Telomere/metabolism ; Longitudinal Studies ; Leukocytes/metabolism ; Case-Control Studies ; Adult ; Oxidation-Reduction ; Prognosis ; *Telomere Homeostasis ; },
abstract = {INTRODUCTION: Small cell lung cancer (SCLC) is an aggressive malignant disease with poor survival outcomes. The aim of this study was to investigate leukocyte telomere length (LTL) and redox status parameters during chemotherapy and evaluate their prognostic potential based on the hypothesis that shorter LTL and oxidative stress burden correlate with poorer survival.

MATERIALS AND METHODS: This longitudinal study included 60 SCLC patients and 73 healthy controls. Leukocyte telomere length was measured by quantitative PCR (qPCR) method, while redox status parameters (MDA - malondialdehyde, IMA - ischemia-modified albumin, PON1 - paraoxonase 1, redox index) were determined by spectrophotometric methods before, after two and after four cycles of chemotherapy.

RESULTS: All measured parameters showed significant differences between patients and controls, except the oxy-score (P < 0.001). Significant differences in IMA, PON1 and redox index were observed between SCLC patient groups at different time points (P < 0.001). Significant differences in IMA and PON1 were observed between SCLC survival groups, with higher values found in survivors after two chemotherapy cycles (P < 0.001). Redox index was the highest in the pre-chemo group (P = 0.019). Among patients who died, PON1 activity differed significantly between those who died within 2 months and after 4 months (P = 0.028). Kaplan-Meier analysis showed that LTL and PON1 were significant predictors of survival, with values below the 25th percentile associated with a higher risk of death.

CONCLUSIONS: Leukocyte telomere length and PON1 are potential prognostic biomarkers for SCLC survival, suggesting their potential use in non-invasive biomarker panels for improved patient stratification.},
}

Humans
Male
Female
*Oxidative Stress/drug effects
*Lung Neoplasms/drug therapy/genetics/metabolism/mortality
*Small Cell Lung Carcinoma/drug therapy/genetics/metabolism/mortality
Middle Aged
Aged
Aryldialkylphosphatase/metabolism
*Telomere/metabolism
Longitudinal Studies
Leukocytes/metabolism
Case-Control Studies
Adult
Oxidation-Reduction
Prognosis
*Telomere Homeostasis

@article {pmid40463079,
year = {2025},
author = {Garbouchian, A and Cestari Moreno, N and Dey, A and Opresko, P and Barnes, R},
title = {Oxidative Base Damage to Telomeres Sensitizes Cancer Cells to ATR Inhibition.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.10.653274},
pmid = {40463079},
issn = {2692-8205},
abstract = {Targeted inhibition of DNA damage response proteins has received significant clinical attention owing to the success of PARP inhibitors. Due to the loss of the G1/S checkpoint, cancer cells are reliant on the G2/M checkpoint to cope with elevated DNA replication stress. We previously demonstrated a single induction of 8-oxo-guanine at telomeres in cancer cells was sufficient to induce replication stress, but was well tolerated at the cellular level. Here, we found inhibition of ATR, Chk1, or Wee1 after induction of telomere oxidative stress significantly induced genome instability and reduced cell viability. This occurred at doses markedly less than those required to increase instability in non-cancer cells. We determined the mechanism of this instability is due to cells progressing through S-phase with telomere damage and exiting G2-phase prematurely, prolonging their mitosis. This study demonstrates targeted oxidative base damage at telomeres can enhance the therapeutic efficacy of ATR inhibition in cancer.},
}

@article {pmid40459934,
year = {2025},
author = {Poeschla, M and Arora, UP and Walne, A and McReynolds, LJ and Niewisch, MR and Giri, N and Zeigler, LP and Gusev, A and Machiela, MJ and Tummala, H and Savage, SA and Sankaran, VG},
title = {Polygenic modifiers impact penetrance and expressivity in telomere biology disorders.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI191107},
pmid = {40459934},
issn = {1558-8238},
abstract = {BACKGROUND: Telomere biology disorders (TBDs) exhibit incomplete penetrance and variable expressivity, even among individuals harboring the same pathogenic variant. We assessed whether common genetic variants associated with telomere length combine with large-effect variants to impact penetrance and expressivity in TBDs.

METHODS: We constructed polygenic scores (PGS) for telomere length in the UK Biobank to quantify common variant burden, and assessed the PGS distribution across patient cohorts and biobanks to determine whether individuals with severe TBD presentations have increased polygenic burden causing short telomeres. We also characterized rare TBD variant carriers in the UK Biobank.

RESULTS: Individuals with TBDs in cohorts enriched for severe pediatric presentations have polygenic scores predictive of short telomeres. In the UK Biobank, we identify carriers of pathogenic TBD variants who are enriched for adult-onset manifestations of TBDs. Unlike individuals in disease cohorts, the PGS of adult carriers do not show a common variant burden for shorter telomeres, consistent with the absence of childhood-onset disease. Notably, TBD variant carriers are enriched for idiopathic pulmonary fibrosis diagnoses, and telomere length PGS stratifies pulmonary fibrosis risk. Finally, common variants affecting telomere length were enriched in enhancers regulating known TBD genes.

CONCLUSION: Common genetic variants combine with large-effect causal variants to impact clinical manifestations in rare TBDs. These findings offer a framework for understanding phenotypic variability in other presumed monogenic disorders.

FUNDING: This work was supported by National Institutes of Health grants R01DK103794, R01HL146500, R01CA265726, R01CA292941, and the Howard Hughes Medical Institute.},
}

@article {pmid40458946,
year = {2025},
author = {Koç Öztürk, F and Usta Özdemir, S and Karakılıç, E and Sılan, F},
title = {A Comprehensive Diagnostic Assessment of Thyroid Nodules Utilizing Scintigraphy and Telomere Lengths (T/S ratios).},
journal = {Molecular imaging and radionuclide therapy},
volume = {34},
number = {2},
pages = {97-106},
pmid = {40458946},
issn = {2146-1414},
abstract = {OBJECTIVES: This study aims to evaluate the effectiveness and role of telomere length measurements in leukocytes, plasma free cell DNA (cfDNA), and biopsy cells, along with technetium-99m (Tc-99m) methoxyisobutylisonitrile (MIBI) scintigraphy, as non-invasive methods for diagnosing malignant thyroid lesions.

METHODS: Data from 128 patients, who underwent ultrasound, Tc-99m MIBI scintigraphy, and fine-needle biopsy with a preliminary diagnosis of malignant thyroid nodules, were analyzed. In 98 patients, telomere lengths in leukocytes (from blood), cfDNA (from plasma), and biopsy cells were measured using the quantitative polymerase chain reaction method, and the relative telomere/single copy gene (T/S) ratio was calculated. Based on cytological examination results, patients were categorized into three groups: malignant, benign, and suspicious. Group differences were analyzed using the Kruskal-Wallis and Chi-square tests, and correlations between variables were examined with Spearman correlation analysis.

RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Tc-99m MIBI scintigraphy for diagnosing malignant thyroid nodules were 64.70%, 79.16%, 29.72%, 83.51%, and 67.96%, respectively. While these results align with the literature, the positive predictive value was notably lower. No significant differences were observed in telomere lengths (T/S ratios) in leukocytes, plasma, or tissue between the groups.

CONCLUSION: Tc-99m MIBI scintigraphy demonstrates reasonable diagnostic accuracy for identifying malignancy in thyroid nodules. Contrary to limited reports, telomere length measurements may not be a reliable method for predicting thyroid malignancy. Larger studies are needed to further explore these findings.},
}

@article {pmid40456754,
year = {2025},
author = {Peng, G and Qin, Y and Yan, Z and He, M and Zhao, Y and Jiang, N and Wei, C},
title = {The high-quality telomere-to-telomere genome assembly of the earthworm (Amynthas aspergillum).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {931},
pmid = {40456754},
issn = {2052-4463},
support = {Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; Grant No. 82473808//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {Animals ; *Oligochaeta/genetics ; *Telomere/genetics ; *Genome ; },
abstract = {Earthworms have been extensively studied as ancient soil invertebrates, that are highly diverse. Previous studies of these invertebrates have mainly focused on their ecosystem services, medicinal value, and ecological habits. However, their genomic analysis remains inadequate. In this study, we generated the first high-quality telomere-to-telomere (T2T) assembly of the genome of the earthworm, Amynthas aspergillum (Perrier, 1872), which belongs to the genus Amynthas of the family Megascolecidae. The T2T assembly was 758.86 Mb with an N50 contig size of 16.59 Mb. The sequences were anchored to 43 chromosomes (2n = 2x = 86) with a coverage of 98.43% (746.95 Mb), and 83 telomeres were detected. In addition, we also predicted 35,723 protein-coding genes with 97.02% being functionally annotated. This T2T genome assembly will establish substantial groundwork for exploring the evolutionary mechanisms of the earthworm genome and enhance the specificity of its pharmacological effects.},
}

Animals
*Oligochaeta/genetics
*Telomere/genetics
*Genome

@article {pmid40456748,
year = {2025},
author = {de Andrade, KC and Pinto, EM and Zhao, T and Zeigler, LP and Kim, J and Giri, N and Haley, JS and McReynolds, LJ and Florez-Vargas, O and Phillips, AH and Kriwacki, RW and Akinniyi, SA and Cohen, SB and Emerson, MR and Smelser, DT and Urban, GM and Fridman, C and Zambetti, GP and Bryan, TM and Carey, DJ and Garcia, CK and Stewart, DR and Savage, SA},
title = {TERT c.3150 G > C (p.K1050N): a founder Ashkenazi Jewish variant associated with telomere biology disorders.},
journal = {NPJ genomic medicine},
volume = {10},
number = {1},
pages = {46},
pmid = {40456748},
issn = {2056-7944},
support = {R01 HL093096/NH/NIH HHS/United States ; },
abstract = {Pathogenic germline variants in telomerase (TERT) cause telomere biology disorders (TBDs) and are associated with bone marrow failure, pulmonary fibrosis, and other complications. TERT c.3150 G > C (p.K1050N) is frequent in the Ashkenazi Jewish (ASH) population and has been identified in ASH families with TBDs. Whole-genome sequencing of 96 p.K1050N heterozygotes from the UK Biobank and All of Us databases revealed a shared haplotype block, supporting a founder effect. Analyses of 15 additional p.K1050N cases validated this haplotype and identified mitochondrial and Y-STR haplogroups consistent with ASH ancestry. Clinical assessments showed that p.K1050N contributes to TBD phenotypes and shortened telomeres, while population data suggest incomplete penetrance. p.K1050N reduces telomerase activity and processivity, and decreases PCNA expression and BrdU incorporation, impairing cell proliferation. Our findings establish TERT p.K1050N as an ASH founder variant associated with TBDs, underscoring the need for genetic screening and long-term clinical studies.},
}

@article {pmid40455262,
year = {2025},
author = {Benetos, A and Fritsch, C and Horton, E and Lenotre, L and Toupance, S and Villemonais, D},
title = {Stochastic branching models for the telomeres dynamics in a model including telomerase activity.},
journal = {Journal of mathematical biology},
volume = {91},
number = {1},
pages = {8},
pmid = {40455262},
issn = {1432-1416},
mesh = {*Telomerase/metabolism ; Stochastic Processes ; Humans ; *Telomere/physiology/metabolism/genetics ; Mathematical Concepts ; *Models, Biological ; Telomere Homeostasis ; Cellular Senescence/genetics ; *Models, Genetic ; Aging/genetics ; Computer Simulation ; },
abstract = {Telomeres are repetitive sequences of nucleotides at the end of chromosomes, whose evolution over time is intrinsically related to biological ageing. In most cells, with each cell division, telomeres shorten due to the so-called end replication problem, which can lead to replicative senescence and a variety of age-related diseases. On the other hand, in certain cells, the presence of the enzyme telomerase can lead to the lengthening of telomeres, which may delay or prevent the onset of such diseases but can also increase the risk of cancer. In this article, we propose a stochastic representation of this biological model, which takes into account multiple chromosomes per cell, the effect of telomerase, different cell types and the dependence of the distribution of telomere length on the dynamics of the process. We study theoretical properties of this model, including its long-term behaviour. In addition, we investigate numerically the impact of the model parameters on biologically relevant quantities, such as the Hayflick limit and the Malthusian parameter of the population of cells.},
}

*Telomerase/metabolism
Stochastic Processes
Humans
*Telomere/physiology/metabolism/genetics
Mathematical Concepts
*Models, Biological
Telomere Homeostasis
Cellular Senescence/genetics
*Models, Genetic
Aging/genetics
Computer Simulation

@article {pmid40452427,
year = {2025},
author = {Szejner-Sigal, A and Heidinger, BJ and Kucera, AC and Kittilson, JD and Torson, AS and Rinehart, JP and Yocum, GD and Bowsher, JH and Greenlee, KJ},
title = {Hypoxia extends lifespan but does not alter telomere length or oxidative stress in a solitary bee (Megachile rotundata).},
journal = {The Journal of experimental biology},
volume = {},
number = {},
pages = {},
doi = {10.1242/jeb.250500},
pmid = {40452427},
issn = {1477-9145},
support = {5P30GM103332//COBRE/ ; NACA 58-3060-5-019//Agricultural Research Service/ ; 3060-21220-03200D//Agricultural Research Service/ ; NSF-IOS-0953297//Division of Integrative Organismal Systems/ ; },
abstract = {Stress can influence lifespan in both positive and negative ways, depending on exposure intensity and duration. However, mechanisms driving positive stress effects on lifespan remain poorly understood. Prolonged hypoxia extends the lifespan of overwintering prepupal Megachile rotundata. Here, we explore telomere length and reduced oxidative stress as potential mechanisms of this extended lifespan. We hypothesized high antioxidant capacity under hypoxia reduces oxidative damage and telomere loss. We exposed prepupae to 10, 21 or 24% oxygen for up to 9 months and measured monthly survival, telomere length, antioxidant capacity, and lipid peroxidation across treatment duration for prepupae and adults. After 9 months of exposure, survival was highest in hypoxia and lowest in hyperoxia. Telomere length did not differ among oxygen treatments but increased in adults compared to prepupae. Total antioxidant capacity and lipid peroxidation showed no significant differences among oxygen treatments, suggesting compensatory responses to maintain baseline oxidative levels.},
}

@article {pmid40451968,
year = {2025},
author = {Li, Q and Yu, X},
title = {Telomere-to-telomere sequence of mouse haploid stem cells.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {40451968},
issn = {1869-1889},
}

@article {pmid40446331,
year = {2025},
author = {Cabral-de-Mello, DC and Gasparotto, AE and Rico-Porras, JM and Ferretti, ABSM and Mora-Ruiz, P and Alves-Gomes, RT and Lourejan, V and Scudeler, EL and Lorite, P and Bardella, VB},
title = {First insights into the satellitomes and new evidence for the absence of canonical insect telomere in the Neuroptera order.},
journal = {Genome},
volume = {},
number = {},
pages = {},
doi = {10.1139/gen-2025-0018},
pmid = {40446331},
issn = {1480-3321},
abstract = {Repetitive DNA is a major component of eukaryotic genomes, playing structural and evolutionary roles. However, in Neuroptera, its characterization remains unexplored. To address this, we analyzed the satellitomes of two Chrysopini (Chrysopidae) species using cytogenomic tools, also investigating telomeric and ribosomal DNA (rDNA). The canonical insect telomeric motif was absent, and rDNA clusters showed variation compared to other neuropterans, despite karyotype stasis (2n = 12, XY). Satellite DNA (satDNA) abundance varied between Ceraeochrysa cincta and Chrysopa pallens, representing a minor fraction of their repetitive DNA content. Notably, no satDNA sequences were shared between species, suggesting a rapid turnover. Exceptionally, the second most abundant satDNA in each species showed low sequence similarity and a putative common origin. A relationship between satDNAs and transposable elements (TEs) was also observed. Chromosome mapping revealed that abundant satDNAs accumulated in euchromatin, providing insights into their genomic distribution. These findings enhance our understanding of satDNA organization in Neuroptera, offering a foundation for future genome assembly efforts and evolutionary studies in these insects.},
}

@article {pmid40445797,
year = {2025},
author = {Benson, DM and Perez, DJP and DeNardo, DF},
title = {Why are telomeres the length that they are? Insight from a phylogenetic comparative analysis.},
journal = {Evolution; international journal of organic evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/evolut/qpaf119},
pmid = {40445797},
issn = {1558-5646},
abstract = {Telomeres are short repeating nucleotide sequences at the ends of chromosomes that shorten with every cellular replication. Despite the importance of keeping telomere length within a critical homeostatic range, adult telomere length can differ by two orders of magnitude across vertebrate species. Why telomere length varies so widely remains unknown, though popular hypotheses suggest that body size, lifespan, and endothermy are key variables that have coevolved with telomere length. To test the relationship among telomere length, telomerase activity (which extends telomeres), and these variables, we modeled the evolution of telomere length across 122 vertebrate species. We failed to find an influence of body mass, lifespan, or baseline metabolism on telomere length. However, we found a significant interactive effect between baseline metabolism and body mass. The presence of telomerase activity was positively correlated with telomere length across the 58 species where data for both existed. Taken together, our findings suggest that body mass may have differentially influenced the evolution of telomere length in endotherms and ectotherms and indicate that telomerase activity and telomere length may have coevolved.},
}

@article {pmid40444520,
year = {2025},
author = {Hwa, HL and Feng, JY and Huang, CY and Hsieh, YP and Wei, HS and Shen, AC},
title = {Association between childhood polyvictimization, telomere length, and post-traumatic stress disorder.},
journal = {Pediatrics international : official journal of the Japan Pediatric Society},
volume = {67},
number = {1},
pages = {e70101},
doi = {10.1111/ped.70101},
pmid = {40444520},
issn = {1442-200X},
support = {105-S3060//National Taiwan University Hospital/ ; FR012//National Taiwan University Children and Family Research Center Sponsored by CTBC Charity Foundation/ ; },
mesh = {Humans ; *Stress Disorders, Post-Traumatic/etiology/epidemiology/psychology/genetics ; Male ; Female ; Child ; Taiwan/epidemiology ; *Child Abuse/psychology ; Longitudinal Studies ; *Telomere ; Case-Control Studies ; },
abstract = {BACKGROUND: Child maltreatment is related to adverse psychosocial outcomes and may be associated with telomere erosion. Longitudinal research on mental health problems and telomere length (TL) in victimized children in Asian societies is scarce. In this study, we evaluated the associations of childhood polyvictimization with TL and longitudinal psychological problems.

METHODS: Subcohorts were obtained from a national, proportionately stratified sample of fourth-grade Taiwanese students recruited in 2014; the sample comprised 70 high-risk group participants (experience of polyvictimization) and 129 controls (nonvictims). For these 199 participants, TL was analyzed in 2014, whereas self-report post-traumatic stress disorder (PTSD) symptom scales and psychological disorder/symptom were completed in 2014, 2016, 2018, and 2021.

RESULTS: Childhood polyvictimization was associated with prolonged high PTSD symptom scores in 2014, 2016, 2018, and 2021. TL was significantly shorter among the polyvictims than among the nonvictims.

CONCLUSIONS: This study demonstrated an association between childhood polyvictimization and prolonged PTSD in children. Our findings also support the assertion that childhood polyvictimization is associated with telomere erosion.},
}

Humans
*Stress Disorders, Post-Traumatic/etiology/epidemiology/psychology/genetics
Male
Female
Child
Taiwan/epidemiology
*Child Abuse/psychology
Longitudinal Studies
*Telomere
Case-Control Studies

@article {pmid40444469,
year = {2025},
author = {Travieso, SG and Ortiz, GU},
title = {Increased muscle satellite cell content and preserved telomere length in response to exercise training in FSHD: implications for sarcopenia and longevity.},
journal = {The Journal of physiology},
volume = {},
number = {},
pages = {},
doi = {10.1113/JP288768},
pmid = {40444469},
issn = {1469-7793},
support = {2019/11820-5;2022/15078-4//São Paulo Research Foundation (FAPESP)/ ; },
}

@article {pmid40440898,
year = {2025},
author = {Fan, G and Liu, Q and Fang, Q and Luo, F and Huang, X and Li, H and Guo, W and Liu, B and Yan, L and Hu, L and Xiong, C and Cao, Z and Chen, X and Chen, Z and Wei, J and Wang, Y and Lei, X and Song, L},
title = {Prenatal exposure to PM2.5 constituents and newborn leukocyte telomere length in a prospective study: Windows of susceptibility and modification by maternal folic acid supplementation.},
journal = {Journal of hazardous materials},
volume = {494},
number = {},
pages = {138747},
doi = {10.1016/j.jhazmat.2025.138747},
pmid = {40440898},
issn = {1873-3336},
abstract = {Prenatal exposure to fine particulate matter (PM2.5) is related to alterations in newborn telomere length (TL), an indicator of cellular aging. However, the specific effects of PM2.5 constituents and windows of susceptibility are unknown. We aimed to identify the susceptibility windows for prenatal PM2.5 constituents affecting newborn leukocyte TL (LTL) and examine the modifying role of folic acid (FA) supplementation. This study involved 741 maternal-infant dyads from a birth cohort in Wuhan, China. We applied multiple linear regression, distributed lag models, and three multi-pollutant approaches to explore the effects of PM2.5 constituents on newborn LTL. Prenatal PM2.5 constituent exposures were related to shorter newborn LTL. Each 5 µg/m[3] increase in organic matter (OM) and nitrate (NO3[-]), and each 1 µg/m[3] increase in black carbon (BC), ammonium (NH4[+]), and sulfate (SO4[2-]) during the third trimester were related to reductions in LTL of 3.99 % (95 % confidence interval [CI]: -6.36 %, -1.56 %), 6.31 % (95 % CI: -10.67 %, -1.73 %), 6.63 % (95 % CI: -9.87 %, -3.27 %), 3.69 % (95 % CI: -5.99 %, -1.34 %), and 3.00 % (95 % CI: -5.03 %, -0.92 %), respectively. The mixture of PM2.5 constituents was related to shorter newborn LTL, predominantly driven by OM and BC. The detrimental effects of OM, BC, NH4[+], and NO3[-] on newborn LTL were more pronounced in individuals without FA supplementation (all P for interaction < 0.05). Our findings identify the third trimester as a susceptibility window for PM2.5 constituent-induced LTL shortening, with OM and BC as the primary contributors. FA supplementation may help mitigate these effects, highlighting its potential as an intervention strategy.},
}

@article {pmid40440483,
year = {2025},
author = {Srour, L and Qannan, A and Oshima, J and Megarbane, A and Bejaoui, Y and El Hajj, N},
title = {Investigating telomere length in progeroid syndromes: implications for aging disorders.},
journal = {Aging},
volume = {17},
number = {},
pages = {},
doi = {10.18632/aging.206255},
pmid = {40440483},
issn = {1945-4589},
abstract = {Progeroid syndromes are rare genetic disorders that impact patients' health and lifespans and are characterized by symptoms that mimic the normal aging process. Telomere length is one of the aging hallmarks, a phenomenon linked to cellular aging. Telomere attrition was observed in different progeroid syndromes, such as Nijmegen breakage syndrome patients and Werner syndrome, indicating its contribution to the progeroid phenotype. However, whether it is a common feature in all progeroid syndromes is still unclear. Therefore, in this study, we aimed to estimate telomere length using the DNA methylation-based estimator of human telomere length in publicly available DNA methylation data from patients with Werner Syndrome, Hutchinson-Gilford Progeria Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, and Dyskeratosis congenita, along with additional data provided by our laboratory from patients with Cerebroretinal Microangiopathy with Calcifications and Cysts and Wiedemann-Rautenstrauch Syndrome. Our findings revealed that certain progeroid syndromes, including classical Werner Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, and Dyskeratosis congenita, have significant telomere attrition conversely to Hutchinson-Gilford Progeria Syndrome, Cerebroretinal Microangiopathy with Calcifications and Cysts, Wiedemann-Rautenstrauch Syndrome, and atypical Werner Syndrome. In conclusion, this study addresses a critical gap by providing new insights into the role of telomere attrition across different progeroid conditions. Further research is needed to elucidate the effect of telomere attrition on progeroid syndromes and its implications.},
}

@article {pmid40438983,
year = {2025},
author = {Nurelegne, HT and Thompson, MB and de Andrade, KC and Thompson, AS and McReynolds, LJ and Niewisch, MR and Savage, SA},
title = {Germline PARN Variants in Telomere Biology Disorders and Challenges in Variant Curation.},
journal = {Molecular genetics & genomic medicine},
volume = {13},
number = {6},
pages = {e70107},
pmid = {40438983},
issn = {2324-9269},
support = {//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; },
mesh = {Humans ; *Germ-Line Mutation ; *Exoribonucleases/genetics ; *Telomere/genetics ; Dyskeratosis Congenita/genetics ; },
abstract = {BACKGROUND: PARN encodes poly(A)-specific ribonuclease, a 3 exoribonuclease important in regulating RNA stability and maturation. Rare germline PARN variants have been reported in telomere biology disorders (TBDs) leading to its inclusion on gene panels for bone marrow failure syndromes and pulmonary diseases.

METHODS: To understand the extent of germline PARN variation in human disease, we conducted a comprehensive literature review, curated the TBD-associated PARN variants using AutoGVP and in silico prediction tools (MetaSVM, REVEL, and/or CADD) and assessed their frequency in the gnomAD database.

RESULTS: Ninety-three unique PARN variants were identified in the literature as present in individuals or families affected by TBDs, but clinical features were not consistently reported. Forty-one variants (44.1%) were classified as pathogenic or likely pathogenic. These variants were spread across the entire gene with no obvious clustering. gnomAD data were notable for a paucity of common variants and metrics suggesting PARN variation would be tolerated.

CONCLUSION: The extent to which specific PARN variants can be associated with TBD etiology is limited due to incomplete literature, clinical data, lack of robust functional assays, and high frequency of rare variants.},
}

Humans
*Germ-Line Mutation
*Exoribonucleases/genetics
*Telomere/genetics
Dyskeratosis Congenita/genetics

@article {pmid40437344,
year = {2025},
author = {Huang, HY and Sheen, KH and Hung, CY and Chang-Chien, J and Wang, SL and Ho, CH and Tsai, HJ and Yao, TC},
title = {Association between telomere length and atopic dermatitis among school-age children.},
journal = {Clinical and translational allergy},
volume = {15},
number = {6},
pages = {e70066},
doi = {10.1002/clt2.70066},
pmid = {40437344},
issn = {2045-7022},
support = {MOST 109-2314-B-182-042-MY3//National Science and Technology Council, Taiwan/ ; NSTC 111-2314-B-400-040-MY3//National Science and Technology Council, Taiwan/ ; NSTC 112-2314-B-182-030-MY3//National Science and Technology Council, Taiwan/ ; CMRP3N0371∼3//Chang Gung Medical Foundation/ ; CMRPG3J0121∼3//Chang Gung Medical Foundation/ ; CMRPG3J1711∼2//Chang Gung Medical Foundation/ ; CMRPG3M1831∼3//Chang Gung Medical Foundation/ ; },
abstract = {BACKGROUND: Atopic dermatitis is a common chronic skin disease in children. Whether telomere length is associated with atopic dermatitis remains unclear. This population-based case-control study aimed to investigate the association between telomere length and atopic dermatitis in school-age children.

METHODS: In this cross-sectional analysis, we included 1084 singleton term-born children (608 males; mean age 6.4 years) from the Longitudinal Investigation of Global Health in Taiwanese Schoolchildren cohort. Telomere length was measured using quantitative real-time polymerase chain reaction, log-transformed and was analyzed in quartiles. The main outcome was atopic dermatitis defined as having physician-diagnosed atopic dermatitis and the presence of atopic dermatitis in the last 12 months. Regression analyses were used to assess the relationship between telomere length and atopic dermatitis.

RESULTS: Telomere length was significantly inversely associated with childhood atopic dermatitis after adjusting for child's age, sex, overweight or obesity, birth season, childhood allergic diseases, environmental tobacco smoke, parental history of allergic diseases, parental educational level, and breastfeeding status (p_trend = 0.01). Specifically, when telomere length was classified into quartiles, children in the shortest (fourth) telomere length quartile had a 1.88-fold higher probability of atopic dermatitis compared to those in the longest (first) quartile (95% confidence interval: 1.13-3.14). Stratified analyses showed that the associations were stronger in males and non-breastfed children, with no significant associations observed in females or breastfed children.

CONCLUSION: This study provides new evidence suggesting an association between shorter telomere length and atopic dermatitis in school-age children.},
}

@article {pmid40431584,
year = {2025},
author = {Dutra, LML and Souza, FS and Vasconcellos, AS and Young, RJ and Schork, IG},
title = {Telomere Tales: Exploring the Impact of Stress, Sociality, and Exercise on Dogs' Cellular Aging.},
journal = {Veterinary sciences},
volume = {12},
number = {5},
pages = {},
pmid = {40431584},
issn = {2306-7381},
support = {309124/2022-0//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; 206418/2014-0//National Council for Scientific and Technological Development/ ; 202351/2015-7//National Council for Scientific and Technological Development/ ; 208427/2017-1//National Council for Scientific and Technological Development/ ; },
abstract = {Animal welfare is influenced by the cumulative life experiences of an individual. Among these, exposure to chronic stressors has a significant impact on both physical and mental health, contributing to premature aging-a process linked to telomere shortening. Conversely, positive experiences have been shown to mitigate, delay, and sometimes reverse telomere attrition. This suggests that telomere length could be a reliable indicator for assessing animal welfare. This study explored the association between telomere length and characteristics such as life history, environment, and health in domestic dogs. Buccal swabs collected DNA samples from 250 dogs, and telomere length was quantified via qPCR. Our findings revealed that environmental factors significantly influenced telomere length. Dogs housed in kennels or subjected to low physical activity levels exhibited shorter telomeres. Similarly, dogs living in groups of more than five dogs had shorter telomeres, and male dogs were found to have longer telomeres than females. Overall, these results highlight the importance of environmental conditions in influencing telomere length in dogs and the potential to use this biological indicator to evaluate animal welfare.},
}

@article {pmid40430074,
year = {2025},
author = {Domínguez-de-Barros, A and Sirvent-Blanco, C and García-Pérez, O and Gajate-Arenas, M and García-Ramos, A and Migliazzo, C and Piñero, JE and Lorenzo-Morales, J and Córdoba-Lanús, E},
title = {Telomere Length, Oxidative Stress Markers, and Related miRNAs in Non-Invasive Samples of Mild COVID-19 Cases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
pmid = {40430074},
issn = {1422-0067},
support = {(CB21/13/00100//Consorcio Centro de Investigación Biomédica (CIBER) de Enfermedades Infecciosas (CIBERINFEC)/ ; 2023-2028, PI-CC202302222, Cabildo.23 and PI-2024/0002347//Cabildo Insular de Tenerife/ ; ACIISI 2024//Agencia Canaria de Investigación, Innovación y Sociedad de la Información/ ; Ministerio de Sanidad, Spain.//Ministerio de Sanidad, Spain./ ; },
mesh = {Humans ; *Oxidative Stress ; *MicroRNAs/genetics/blood/metabolism ; *COVID-19/genetics/metabolism/pathology/blood ; Male ; Female ; Middle Aged ; Biomarkers/blood/metabolism ; Adult ; Aged ; SARS-CoV-2 ; *Telomere/metabolism/genetics ; Case-Control Studies ; 8-Hydroxy-2'-Deoxyguanosine ; Thiobarbituric Acid Reactive Substances/metabolism ; Saliva/metabolism ; *Telomere Homeostasis ; },
abstract = {Oxidative stress and inflammation influence immune response and epigenetic mechanisms in infectious diseases. In mild COVID-19, host-encoded miRNA profiles remain underexplored, although they reveal mechanistic insights into disease pathogenesis. This study evaluated ageing and oxidative stress biomarkers (telomere length (TL), TBARS, 8-OHdG, and circulating related-miRNA expression) in 75 mild cases and 30 non-COVID-19 controls. TL correlated with age (R = -0.384, p = 0.005) and was shorter in cases compared to controls (rTL 1.46 ± 0.51 vs. 0.99 ± 0.37; p < 0.001), being similar between saliva and blood samples (p = 0.917). miR-138-5p was upregulated in COVID-19 cases (p = 0.026) and correlated with 8-OHdG (R = 0.403, p = 0.05), which was increased in cases (p = 0.040); miR-210-3p was downregulated in infected individuals (p = 0.008), while miR-182-5p expression correlated with TBARS (R = 0.582, p = 0.018). miR-34a-5p and miR155-5p expression was not altered in mild COVID-19. These findings suggest early systemic cellular damage in mild COVID-19 and highlight miR-138-5p and miR-182-5p as potential early biomarkers of oxidative stress.},
}

Humans
*Oxidative Stress
*MicroRNAs/genetics/blood/metabolism
*COVID-19/genetics/metabolism/pathology/blood
Male
Female
Middle Aged
Biomarkers/blood/metabolism
Adult
Aged
SARS-CoV-2
*Telomere/metabolism/genetics
Case-Control Studies
8-Hydroxy-2'-Deoxyguanosine
Thiobarbituric Acid Reactive Substances/metabolism
Saliva/metabolism
*Telomere Homeostasis

@article {pmid40429722,
year = {2025},
author = {Mejía-Ortiz, P and Genis-Mendoza, AD and Ramírez Villanueva, R and López Ramírez, S and Guzmán Sánchez, R and Fernández, T and Sigg-Alonso, J and Nicolini-Sánchez, H},
title = {Shorter Telomere Length in Individuals with Neurocognitive Disorder and APOE ε4 Genotype.},
journal = {International journal of molecular sciences},
volume = {26},
number = {10},
pages = {},
doi = {10.3390/ijms26104577},
pmid = {40429722},
issn = {1422-0067},
mesh = {Humans ; Male ; Female ; Aged ; Middle Aged ; *Apolipoprotein E4/genetics ; Genotype ; *Telomere Shortening/genetics ; *Telomere/genetics ; *Neurocognitive Disorders/genetics ; *Cognitive Dysfunction/genetics ; Risk Factors ; Aged, 80 and over ; },
abstract = {Neurocognitive disorders (NCD) are neurodegenerative diseases characterized by decline or loss of cognitive functions. Aging and the APOE genotype have been identified as major risk factors. Telomere length (TL) has been proposed as a biomarker of aging, with shorter TL associated with cognitive decline. This study investigated the relationship between TL and the APOE genotype in individuals with cognitive impairments (CIs). A total of 170 participants aged >55 years were included. Cognitive function was assessed using the MMSE and MoCA tests. Relative telomere quantification and APOE genotype were determined by real-time PCR. A significant association was observed between shorter TL and an increased risk of CI (p < 0.001). Although APOE ε4 is a known genetic risk factor, its association with CI was less clear in this study population, as a considerable proportion of ε4 carriers did not present cognitive impairment (p < 0.05). However, ε4 carriers with CI tended to have shorter TL than those with non-cognitive impairment (NCI-SMC). Furthermore, fewer years of education were strongly correlated with higher CI risk (p < 0.0001). Overall, individuals with both shorter telomeres and lower educational levels exhibited the highest risk of CI. APOE ε4 may contribute to telomere shortening.},
}

Humans
Male
Female
Aged
Middle Aged
*Apolipoprotein E4/genetics
Genotype
*Telomere Shortening/genetics
*Telomere/genetics
*Neurocognitive Disorders/genetics
*Cognitive Dysfunction/genetics
Risk Factors
Aged, 80 and over

@article {pmid40418996,
year = {2025},
author = {Mavioglu, RN and Gumpp, AM and Hummel, EM and Moser, DA and Ammerpohl, O and Behnke, A and Mack, M and Kolassa, IT},
title = {Telomere-mitochondrial dynamics differ depending on childhood maltreatment history, catabolic postpartum state, and developmental period.},
journal = {Brain, behavior, and immunity},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.bbi.2025.05.022},
pmid = {40418996},
issn = {1090-2139},
abstract = {Telomere attrition, a hallmark of aging, is linked to high-energy demand states like early development and biological or psychological stress. Metabolic regulation of telomere length (TL) may occur in these states as part of an energetic trade-off, prioritizing immediate needs over long-term requirements such as telomere maintenance, though this has not been observed in healthy humans. We examined associations between TL and mitochondrial bioenergetics, density, and DNA markers in immune cells of women at 1-week (n = 175) and 1-year postpartum (n = 106), depending on their history of childhood maltreatment (CM), and in their newborns (n = 132). At 1-week postpartum, a catabolic state of high energy demand, women with lower mitochondrial energy production efficiency exhibited shorter TL. One year later, these dynamics appeared only in women with a history of CM. In newborns, TL was shorter when mitochondrial density-normalized routine and ATP production-related respiration was higher. Mitochondrial DNA copy number was associated with TL in both mothers and newborns, regardless of the energetic state. Our findings suggest that telomere-mitochondrial dynamics can adapt to the body's energetic needs.},
}

@article {pmid40418329,
year = {2025},
author = {Mattarocci, S},
title = {The DNA damage tolerance factor Rad5 and telomere replication.},
journal = {Current genetics},
volume = {71},
number = {1},
pages = {11},
pmid = {40418329},
issn = {1432-0983},
mesh = {*Telomere/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; *DNA Damage ; *DNA Replication ; Saccharomyces cerevisiae/genetics/metabolism ; *DNA Helicases/genetics/metabolism ; Proliferating Cell Nuclear Antigen/genetics/metabolism ; DNA Repair ; DNA Damage Tolerance ; },
abstract = {The DNA Damage Tolerance pathway (DDT) is one of the major mechanisms for resolving replication fork blocks. A key factor in DDT is the fork-associated clamp PCNA, which can undergo to mono- or polyubiquitination, leading to error-prone or error-free modes of DNA damage bypass, respectively. In the yeast Saccharomyces cerevisiae, Rad5[HLTF/SNF2] factor plays important roles in both pathways: (i) promoting the error-free mode through PCNA polyubiquitination and transient template switching and (ii) interacting with specialized DNA polymerases involved in the error-prone pathway. Rad5 also associates with telomeres, the repetitive DNA regions present at the ends of chromosomes. Telomeric DNA, tightly bound by tandem proteins arrays, poses unique challenges to replication fork progression. Here, I review the current understanding of the link between Rad5 and telomeres and provide evidence that Rad5 binds to yeast telomeres, with notable enrichment during telomere replication. This finding highlights a connection between telomeres and an important DDT factor in unperturbed wild-type cells, raising intriguing possibilities regarding the functional interplay between telomere replication and DNA damage tolerance mechanisms.},
}

*Telomere/genetics/metabolism
*Saccharomyces cerevisiae Proteins/genetics/metabolism
*DNA Damage
*DNA Replication
Saccharomyces cerevisiae/genetics/metabolism
*DNA Helicases/genetics/metabolism
Proliferating Cell Nuclear Antigen/genetics/metabolism
DNA Repair
DNA Damage Tolerance

@article {pmid40417237,
year = {2025},
author = {Eremin, A and Sergeev, A and Kopylov, A and Rodin, V and Malyshev, D and Panova, T and Polyakov, I and Zvereva, M},
title = {Long-read sequencing reveals absence of 5mC in Ogataea parapolymorpha DL-1 genome and introduces telomere-to-telomere assembly.},
journal = {Frontiers in genetics},
volume = {16},
number = {},
pages = {1574332},
pmid = {40417237},
issn = {1664-8021},
abstract = {BACKGROUND: Ogataea parapolymorpha DL-1 is a versatile thermotolerant organism with numerous applications in biotechnology, particularly in the production of recombinant proteins and the study of methanol metabolism and peroxisome functions. This study presents a comprehensive genome and methylome analysis of Ogataea parapolymorpha DL-1 using long-read sequencing technology. The research builds upon previous short-read sequencing efforts, revealing enhancements in genome assembly and epigenomic insights.

METHODS: We used long-read sequencing technology to achieve a telomere-to-telomere (T2T) genome assembly of Ogataea parapolymorpha DL-1. High-quality reads were obtained and assembled de novo, followed by polishing to enhance accuracy. The genome was analyzed to identify coding genes, telomeric motifs, rRNA genes, and methylation patterns, including the detection of 5mC and 6 mA modifications. Epigenetic features were further assessed and validated through liquid chromatography-mass spectrometry.

RESULTS: Key findings include the absence of 5 mC DNA modification and the presence of 6 mA in the genome, unusual telomere regulation mechanism based on the addition of non-telomeric dT and the introduction of long-read enhanced telomere-to-telomere assembly.

CONCLUSION: This work provides deeper insights into the yeast's genome organization and methylation patterns, contributing to the understanding of its genetics and therefore potential biotechnological applications.},
}

@article {pmid40414485,
year = {2025},
author = {Yoshitake, K and Shirasawa, K and Kojima, KK and Asakawa, S and Tanaka, N and Kurokochi, H},
title = {Nearly telomere-to-telomere genome assembly of the L. edodes diploid genome.},
journal = {Fungal genetics and biology : FG & B},
volume = {},
number = {},
pages = {104005},
doi = {10.1016/j.fgb.2025.104005},
pmid = {40414485},
issn = {1096-0937},
abstract = {Lentinula edodes (shiitake mushroom) possesses substantial nutritional and medicinal value. Even though the genomes of several strains have been reported, some essential observations, including the exact chromosome number, still need validation. This study reports a near-telomere-to-telomere assembly of the complete diploid genome of L. edodes strain XR1, a commercially important Japanese strain. We employed the PacBio HiFi long-read sequencing technology combined with single-cell genotyping data and manual curation. The assembled diploid genome comprised 20 chromosomes (10 per haplotype), and significant inter-haplotype variation was observed. Additionally, we identified a novel Penelope-like retrotransposon-Coprina-1_LeEd-specifically localized to the telomeres. This study marks the first report of telomere elongation by the transposition of Coprina. Our findings provide a high-resolution genome resource for L. edodes, consequently elucidating its evolution, genomic structure, and breeding potential. Furthermore, this study establishes a foundation for further research on edible mushroom genetics and biotechnology.},
}

@article {pmid40414363,
year = {2025},
author = {Tavares-Marcos, C and Correia, M and de Jesus, BB},
title = {Telomeres as hallmarks of iPSC aging: a review on telomere dynamics during stemness and cellular reprogramming.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {102773},
doi = {10.1016/j.arr.2025.102773},
pmid = {40414363},
issn = {1872-9649},
abstract = {Telomeres, the protective ends of chromosome, are key to tissue repair and regeneration. Telomere shortening is linked to aging and age-related disorders, while excessive telomerase activity may support tissue regeneration or transformation. Some of the functions of telomeres and telomerase may be mediated by its important role in the process of stemness. Active telomerase, and subsequent telomerase-dependent telomere extension, supports stem-cells self-renewal and pluripotency - essential for tissue healing. During cellular reprogramming, differentiated cells are converted into induced pluripotent stem cells (iPSCs), which resemble embryonic stem cells. During iPSC derivation, telomere length is reset, enhancing iPSCs' regenerative potential. During this process, incomplete telomerase activation and telomere extension can lead to genomic instability and/or haltered cell functionality. Understanding the intricate relation of telomeres, telomerase and stemness may be critical when designing novel cell-based therapies targeting degenerative diseases or to unlock strategies to delay aging. Here, we explore the recent bibliography linking these areas, raising awareness of their important when designing novel breakthroughs in health and longevity.},
}

@article {pmid40411290,
year = {2025},
author = {Wu, J and Bao, RX and Liu, Y and Long, YT and Chen, JT and Shi, YN and Zhang, B and Luo, C and Huang, X and Chen, KS and He, XH and Xie, L and Li, BJ},
title = {Gap-free telomere-to-telomere assembly of the Mangifera persiciforma genome and its evolutionary insights on resistance.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70070},
pmid = {40411290},
issn = {1467-7652},
support = {2024GXNSFBA010399//Natural Science Foundation of Guangxi Province/ ; Gui Ke AD23026320//Science and Technology Talent Special Project of Guangxi/ ; SKLCUSA- b202302//State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources/ ; //The CARSGIT-Guangxi Mango Industry Project (nycytxgxcxtd-2021-06-02)/ ; },
}

@article {pmid40409468,
year = {2025},
author = {Zhu, H and Manson, JE and Cook, NR and Bekele, BB and Chen, L and Kane, KJ and Huang, Y and Li, W and Christen, W and Lee, IM and Dong, Y},
title = {Vitamin D3 and Marine Omega-3 Fatty Acids Supplementation and Leukocyte Telomere Length: 4-Year Findings from the VITAL Randomized Controlled Trial.},
journal = {The American journal of clinical nutrition},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajcnut.2025.05.003},
pmid = {40409468},
issn = {1938-3207},
abstract = {BACKGROUND: Limited studies suggest that vitamin D or omega 3 fatty acids (n-3 FAs) supplementation may be beneficial for telomere maintenance, however, evidence from large randomized clinical trial is lacking. We hypothesized that vitamin D or n-3 FAs supplementation reduce leukocyte telomere length (LTL) attrition overtime by leveraging the VITamin D and OmegA-3 TriaL (VITAL) trial.

METHODS: VITAL is a large, randomized, double-blind, placebo-controlled trial with a 2 x 2 factorial design of vitamin D3 (2,000 IU/day) and marine n-3 FAs (1 g/day) supplements for 5 years among a representative sample of 25,871 US females ≥55 and males ≥50 years of age. The VITAL Telomere study (NCT04386577) included 1054 participants who were evaluated in person at the Harvard Clinical and Translational Science Center. LTL was determined by the Absolute Human Telomere Length Quantification quantitative Polymerase Chain Reaction (PCR) method at baseline, Year 2, and Year 4. The pre-specified primary outcome measures were changes in LTL between baseline, Year 2 and Year 4. Analyses of intervention effect used mixed-effects linear regression models.

RESULTS: LTL was measured in a total of 2,571 samples from the 1031 participants at baseline, year 2, and year 4. Compared to placebo, vitamin D3 supplementation significantly decreased LTL attrition by 0.14 kilo base pairs (kb) (0.01, 0.27) over 4 years (p = 0.039). Overall trend analysis showed that the vitamin D3 supplementation group had LTLs that were about 0.035 kb higher per year of follow-up compared to placebo group (0.002, 0.07, p=0.037). Marine n-3 FAs supplementation had no significant effect on LTL at either year 2 or year 4.

CONCLUSION: 4-years of supplementation with 2000 IU/day vitamin D3 reduced telomere attrition by 140 bp, suggesting that vitamin D3 daily supplementation with or without n-3 FAs might have a role in counteracting telomere erosion or cell senescence. Clinical Trial Registry numberNCT04386577, https://clinicaltrials.gov/study/NCT04386577?term=NCT04386577&rank=1.},
}

@article {pmid40404855,
year = {2025},
author = {Bento, F and Longaretti, M and Pires, VB and Lockhart, A and Luke, B},
title = {RNase H1 and Sen1 ensure that transient TERRA R-loops promote the repair of short telomeres.},
journal = {EMBO reports},
volume = {},
number = {},
pages = {},
pmid = {40404855},
issn = {1469-3178},
support = {552129721- LU 1709/5-1//Deutsche Forschungsgemeinschaft (DFG)/ ; 491145305 - GRK 2859/1//Deutsche Forschungsgemeinschaft (DFG)/ ; 491145305 - GRK 2859/1//Deutsche Forschungsgemeinschaft (DFG)/ ; 552129721- LU 1709/5-1//Deutsche Forschungsgemeinschaft (DFG)/ ; PD/BD/127999/20169//MEC | Fundação para a Ciência e a Tecnologia (FCT)/ ; },
abstract = {Telomere repeat-containing RNA (TERRA) is transcribed at telomeres and forms RNA-DNA hybrids. In budding yeast, the presence of RNA-DNA hybrids at short telomeres promotes homology-directed repair (HDR) and prevents accelerated replicative senescence. RNA-DNA hybrids at telomeres have also been demonstrated to prevent 5'end resection, an essential step for HDR. In accordance, we now demonstrate that, not only the presence, but also the removal, of RNA-DNA hybrids drives HDR at shortened telomeres during replicative senescence. Although RNase H2 is absent from short telomeres, it is quickly compensated for by the recruitment of RNase H1 and Sen1. The recruitment of RNase H1 is essential to allow for the loading of Rad51, consistent with the notion that RNA-DNA hybrids prevent Exo1-mediated end resection. In the absence of RNase H1 or Sen1 function, yeast cultures prematurely enter replicative senescence in the absence of telomerase. Furthermore, the delayed senescence phenotype observed when RNase H2 is deleted, depends on the presence of RNase H1 and Sen1. This study demonstrates the importance of transient RNA-DNA hybrids at short telomeres to regulate senescence.},
}

@article {pmid40404646,
year = {2025},
author = {Nelson, DR and Muvunyi, R and Hazzouri, KM and Tumushime, JC and Nzayisenga, G and Julius, N and Meert, W and Karim, L and Coppieters, W and Munson, KM and Yoo, D and Eichler, EE and Salehi-Ashtiani, K and Twizere, JC},
title = {A near telomere-to-telomere phased reference assembly for the male mountain gorilla.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {842},
pmid = {40404646},
issn = {2052-4463},
support = {R01 HG002385/HG/NHGRI NIH HHS/United States ; },
mesh = {Animals ; *Gorilla gorilla/genetics ; Male ; *Telomere ; *Genome ; Haplotypes ; Endangered Species ; },
abstract = {The endangered mountain gorilla, Gorilla beringei beringei, faces numerous threats to its survival, highlighting the urgent need for genomic resources to aid conservation efforts. Here, we present a near telomere-to-telomere, haplotype-phased reference genome assembly for a male mountain gorilla generated using PacBio HiFi (26.77× ave. coverage) and Oxford Nanopore Technologies (52.87× ave. coverage) data. The resulting non-scaffolded assembly exhibits exceptional contiguity, with contig N50 of ~95 Mbp for the combined pseudohaplotype (3,540,458,497 bp), 56.5 Mbp (3.1 Gbp) and 51.0 Mbp (3.2 Gbp) for each haplotype, an average QV of 65.15 (error rate = 3.1 × 10[-7]), and a BUSCO score of 98.4%. These represent substantial improvements over most other available primate genomes. This first high-quality reference genome of the mountain gorilla provides an invaluable resource for future studies on gorilla evolution, adaptation, and conservation, ultimately contributing to the long-term survival of this iconic species.},
}

Animals
*Gorilla gorilla/genetics
Male
*Telomere
*Genome
Haplotypes
Endangered Species

@article {pmid40397254,
year = {2025},
author = {Li, X and Huang, L and Yan, Y and Rong, Y and Chen, X and Gao, M and Huang, J},
title = {Association of modifiable risk factors and telomere length with five neuroendocrine neoplasms: a bidirectional Mendelian randomization study.},
journal = {Discover oncology},
volume = {16},
number = {1},
pages = {841},
pmid = {40397254},
issn = {2730-6011},
abstract = {BACKGROUND: The timely recognition of modifiable risk factors holds paramount importance in tumor prevention. We aimed to scrutinize the causal relationships between a spectrum of genetically modifiable risk factors and five distinct neuroendocrine neoplasms.

METHODS: A bidirectional two-sample Mendelian randomization (MR) analysis was employed to elucidate the causal relationships between 41 potential risk factors and five neuroendocrine neoplasms.

RESULTS: Height, obesity class 1, 2, and 3, overweight, waist-to-hip ratio, waist circumference, and serum uric acid were identified as factors associated with an augmented risk of colorectal neuroendocrine neoplasms (all p < 0.05). Conversely, a negative correlation was observed between fasting glucose and the risk of colorectal neuroendocrine neoplasms (p = 0.031). Platelet count exhibited a negative correlation with lung neuroendocrine neoplasms (p = 0.02). Moreover, the waist-to-hip ratio demonstrated a negative association with the risk of pancreatic neuroendocrine neoplasms. Atrial fibrillation, mean cell heamoglobin, and mean cell volume were positively associated with the risk of small intestine neuroendocrine neoplasms. In gastric neuroendocrine neoplasms, obesity class 1 and 2, overweight, and telomere length were implicated in their heightened risk. Following adjustment for multiple tests, obesity class 1 remained statistically significant to colorectal neuroendocrine neoplasms, and telomere length maintained significance in association with gastric neuroendocrine neoplasms. The outcomes of reverse MR suggested a bidirectional causal relationship between telomere length and gastric neuroendocrine neoplasms.

CONCLUSION: This study provided genetic evidence for the causal relationships between potentially modifiable risk factors and the risk of five neuroendocrine neoplasms. Therapeutic approaches to these factors may provide a basis for preventing neuroendocrine neoplasms.},
}

@article {pmid40392448,
year = {2025},
author = {Wang, KL and Xi, XX and Zheng, JH},
title = {A Novel Telomere Maintenance Gene-Related Model for Prognosis Prediction in Gastric Cancer.},
journal = {Biochemical genetics},
volume = {},
number = {},
pages = {},
pmid = {40392448},
issn = {1573-4927},
abstract = {Gastric cancer (GC) remains a significant clinical challenge due to its frequent late-stage diagnosis and limited treatment stratification. Telomere maintenance genes (TMGs) are crucial in GC progression, but their prognostic value has not been fully explored. This study is the first to integrate TMGs with machine learning to develop a prognostic model for GC. Using clinical and gene expression data from the TCGA database, differentially expressed genes (DEGs) were identified and intersected with TMGs. Prognostic TMGs were determined through Cox regression and machine learning techniques, including Lasso, random forest, and Xgboost algorithms. A five-gene prognostic model (CCT6A, ELOVL4, PC, PLCL1, RPS4Y1) was developed and validated using TCGA data. The model demonstrated strong predictive performance, with AUCs of 0.71, 0.71, and 0.70 at 1-, 3-, and 5-year survival, respectively. High-risk patients had significantly poorer overall survival (OS). Further analysis of the tumor microenvironment (TME) showed that high-risk patients exhibited increased immune cell infiltration, and TMG-associated pathways such as apoptosis, epithelial-mesenchymal transition (EMT), and IL6/JAK/STAT3 signaling were prominent. High EMT scores were linked to worse prognosis. In addition, the hub genes were upregulated in GC patients and cells, correlating with decreased OS. PLCL1 significantly promoted GC cell proliferation, migration, and invasion, and it also activated the inflammation-related pathways in GC. In conclusion, this study not only highlights the prognostic relevance of TMGs in GC but also underscores the clinical translation potential of the prognostic model, offering novel targets for personalized therapeutic strategies in GC.},
}

@article {pmid40389311,
year = {2025},
author = {de Lange, T},
title = {How Shelterin Orchestrates the Replication and Protection of Telomeres.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041685},
pmid = {40389311},
issn = {1943-0264},
abstract = {Efforts to determine how telomeres solve the end-protection problem led to the discovery of shelterin, a conserved six-subunit protein complex that specifically binds to the long arrays of telomeric TTAGGG repeats at vertebrate chromosome ends. The mechanisms by which shelterin prevents telomeres from being detected as sites of DNA damage and how shelterin prevents inappropriate DNA repair pathways are now largely known. More recently, shelterin has emerged as a central player in solving the second major problem at telomeres: how to complete the duplication of telomeric DNA. This end-replication problem results from the inability of the canonical DNA replication machinery to maintain the DNA at chromosome ends. Shelterin solves this problem by recruiting two enzymes that can replenish the lost telomeric repeats: telomerase and CST-Polα/primase. How shelterin accomplishes these critical tasks is reviewed here.},
}

@article {pmid40389285,
year = {2025},
author = {Antipov, D and Rautiainen, M and Nurk, S and Walenz, BP and Solar, SJ and Phillippy, AM and Koren, S},
title = {Verkko2 integrates proximity ligation data with long-read De Bruijn graphs for efficient telomere-to-telomere genome assembly, phasing, and scaffolding.},
journal = {Genome research},
volume = {},
number = {},
pages = {},
doi = {10.1101/gr.280383.124},
pmid = {40389285},
issn = {1549-5469},
abstract = {The Telomere-to-Telomere Consortium recently finished the first truly complete sequence of a human genome. To resolve the most complex repeats, this project relied on the semi-manual combination of long, accurate PacBio HiFi and ultra-long Oxford Nanopore sequencing reads. The Verkko assembler later automated this process, achieving complete assemblies for approximately half of the chromosomes in a diploid human genome. However, the first version of Verkko was computationally expensive and could not resolve all regions of a typical human genome. Here we present Verkko2, which implements a more efficient read correction algorithm, improves repeat resolution and gap closing, introduces proximity-ligation-based haplotype phasing and scaffolding, and adds support for multiple long-read data types. These enhancements allow Verkko to assemble all regions of a diploid human genome, including the short arms of the acrocentric chromosomes and both sex chromosomes. Together, these changes increase the number of telomere-to-telomere scaffolds by twofold, reduce runtime by fourfold, and improve assembly correctness. On a panel of 19 human genomes, Verkko2 assembles an average of 39 of 46 complete chromosomes as scaffolds, with 21 of these assembled as gapless contigs. Together, these improvements enable telomere-to-telomere comparative genomics and pangenomics, at scale.},
}