@article {pmid40908046,
year = {2025},
author = {Yu, J and Zhang, Y and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association of leucocyte telomere length with incident age-related macular degeneration: a prospective UK Biobank Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327492},
pmid = {40908046},
issn = {1468-2079},
abstract = {PURPOSE: There have been conflicting findings on the role of leucocyte telomere length (LTL) in the risk of age-related macular degeneration (AMD). In this study, we evaluated the associations between LTL and the risk of incident AMD and explored whether age, sex and/or genetic predisposition to AMD can modify these associations.

METHODS: We conducted a longitudinal cohort study involving 332 123 AMD-free participants with complete baseline covariates and LTL data from the UK Biobank. We employed multivariable Cox proportional hazards models to test the association between LTL and AMD incidence, estimating the HRs and 95% CIs. Genetic risk was assessed using polygenic risk score (PRS).

RESULTS: During a median follow-up of 13.63 years, 6754 participants (2.03%) developed AMD. Shorter LTL was not associated with incident AMD risk (HR=1.042, 95% CI: 0.992 to 1.094; p=0.10) after adjusting for multiple confounders. Sex showed an interactive effect with LTL (p=0.01 for interaction) on incident AMD risk, while age and PRS did not modify these associations. We identified a significant association between shorter LTL and incident AMD risk in females (HR=1.093, 95% CI: 1.025 to 1.166; p=0.007), but not in males. Moreover, shorter LTL was associated with thinner photoreceptor segments only in females at both baseline and repeated assessments (β=-0.141 µm, 95% CI: -0.267 to -0.016; β=-0.345 µm, 95% CI: -0.649 to -0.041, p<0.05).

CONCLUSIONS: Shorter LTL increased the risk of incident AMD in females, suggesting LTL as a potential biomarker for AMD development with sex-specific function.},
}

@article {pmid40907145,
year = {2025},
author = {Goetz, SMM and Lucas, T and Finegood, E and Lin, J and Granger, D},
title = {Age and gender intersectionality among African Americans: Salivary uric acid is associated with shorter telomere length in younger adults and men.},
journal = {Psychoneuroendocrinology},
volume = {181},
number = {},
pages = {107588},
doi = {10.1016/j.psyneuen.2025.107588},
pmid = {40907145},
issn = {1873-3360},
abstract = {Age related diseases present disproportionately among African Americans and have been tied to broad social inequalities and accompanying stress. Yet, there is considerable variability among African Americans in susceptibility, highlighting potential connections to both intersectionality and stress-related biological processes. A growing body of research links exposure to racism and discrimination to telomere length (TL)-an indicator of biological aging that is increasingly implicated in explaining stress-related racial health disparities. However, few studies have examined links to accompanying stress processes that may precede TL shortening. This includes examining Uric Acid (UA), which growing evidence suggests may comprise a unique biological aspect of the acute stress response, with implications for both racial health disparities and within-race heterogeneity. In a secondary analysis of a sample of healthy African Americans (N = 103, 33 men; M age = 31.41 years), we assessed the relationship between salivary UA (sUA) and TL. With an eye towards within-group heterogeneity, we also considered the moderating role of age and gender. Our findings revealed a negative association between UA and TL that was most pronounced in African American men and among younger African Americans. We apply an intersectional lens to interpret these results, revealing that different intersections of identity operate through distinct mechanisms. Among men, UA consistently predicted shorter telomeres regardless of discrimination exposure, suggesting biological pathways may be primary. However, among women, the UA/TL relationship was moderated by discrimination-with UA positively predicting TL under low discrimination but showing negative associations under high discrimination conditions. These findings demonstrate that intersectionality operates through multiple pathways simultaneously, with some intersections characterized by biological vulnerabilities while others are defined by social moderation effects. Future research directions should consider the multifaceted influences of UA on TL, recognizing that different intersectional positions may require examination of distinct biological and social mechanisms including potential interventions targeting UA levels to mitigate age-related illnesses and address health disparities among African Americans. Additionally, future studies should examine how additional intersecting systems of oppression might moderate the relationship between UA and TL.},
}

@article {pmid40907117,
year = {2025},
author = {Hu, G and Yu, Y and Yin, Y and Yang, X and Yu, R and Xiang, Q},
title = {Impact of telomere length on autoimmune thyroid disease in Europeans: insights from Mendelian randomization.},
journal = {Clinics (Sao Paulo, Brazil)},
volume = {80},
number = {},
pages = {100765},
doi = {10.1016/j.clinsp.2025.100765},
pmid = {40907117},
issn = {1980-5322},
abstract = {OBJECTIVE: This study aimed to investigate the causal relationship between Telomere Length (TL) and Autoimmune Thyroid Disease (AITD) in Europeans using Mendelian Randomization (MR).

METHODS: Single nucleotide polymorphisms associated with TL and AITD were obtained from genome-wide association studies. MR analysis was conducted using inverse variance weighted as the primary method. Cochran's Q test and leave-one-out sensitivity analysis were employed to assess heterogeneity and robustness, respectively.

RESULTS: TL was significantly associated with reduced genetic susceptibility to Graves' Disease (GD) in Europeans (Odds Ratio [OR = 0.776], 95 % Confidence Interval [95 %CI 0.625-0.964]; p = 0.022). However, no association was found between TL and Autoimmune Thyroiditis (AIT) (OR = 1.474, 95 % CI 0.870-2.497; p = 0.149). Cochran's Q test and leave-one-out sensitivity analysis confirmed that the findings were free of heterogeneity and robust.

CONCLUSION: MR analysis revealed that TL shortening is associated with increased genetic susceptibility to GD in Europeans, but no such association was observed for AIT. Further research is needed to elucidate the mechanisms through which TL influences AITD.},
}

@article {pmid40905409,
year = {2025},
author = {He, H and Yang, X and Wang, K and Ye, Q},
title = {Oxidative DNA damage may promote the development of endometriosis by activating telomerase and extending telomere length: a meta-analysis.},
journal = {Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/1354750X.2025.2557452},
pmid = {40905409},
issn = {1366-5804},
abstract = {OBJECTIVE: To investigate the associations between oxidative DNA damage biomarkers [levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), telomere length (TL), human telomerase reverse transcriptase (hTERT), telomerase activity (TA) and polymorphisms of human 8-oxoguanine glycosylase 1 (hOGG1) or X-ray repair cross-complementing group 4 (XRCC4)] and endometriosis (EMT) by a meta-analysis.

METHODS: Five databases were searched until August 2024. Stata 15.0 was used to estimate pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CIs).

RESULTS: Forty-two studies were included. Overall meta-analysis revealed significantly elevated 8-OHdG (SMD = 1.84; 95%CI = 1.29 - 2.39), TA (SMD = 3.03; 95%CI = 2.07 - 4.00) and hTERT (SMD = 2.55; 95%CI = 1.55 - 3.55) in EMT women compared to controls. Women carrying GG genotype (vs GC + CC: OR = 1.34; 95%CI = 1.00 - 1.78) of hOGG1 rs1052133, TT genotype (vs TG + GG: OR = 2.67; 95%CI = 1.63 - 4.38) and T allele (vs G: OR = 3.49; 95%CI = 2.27 - 5.35) of XRCC4 rs6869366 had a higher risk of developing EMT. Subgroup and trim-and-fill analyses indicated longer TL was a risk factor for EMT.

CONCLUSIONS: 8-OHdG, TA, hTERT, TL, rs1052133 and rs6869366 represent potential prediction biomarkers and treatment targets for EMT.},
}

@article {pmid40903918,
year = {2025},
author = {Lowran, K and Campbell, L and Cismas, E and Wu, CG},
title = {Domain-Specific DNA Binding Activities of BRCA1 Reveal Substrate Preferences for Homologous Recombination and Telomere Regulation.},
journal = {Biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.biochem.5c00333},
pmid = {40903918},
issn = {1520-4995},
abstract = {BRCA1 is a crucial component of homologous recombination (HR), a high-fidelity pathway for repairing double-stranded DNA breaks (DSBs) in human cells. The central region of the BRCA1 protein contains two putative DNA binding domains (DBDs), yet their relative substrate specificities and functional contributions to HR remain unclear. Here, we characterized the DNA binding properties of DBD1 (amino acids 330-554), DBD2 (amino acids 894-1057), and BRCA1 C-terminal (BRCT) repeats using biolayer interferometry. Affinities were determined for single-stranded DNA (ssDNA), double-stranded DNA (dsDNA), and G-quadruplex (G4) DNA. DBD2 exhibited strong and nearly identical binding to all three substrates (Kd = ∼35-44 nM), while the BRCT also bound to each structure similarly, but with lower affinity (Kd = ∼149-184 nM). In contrast, DBD1 showed a distinct preference for dsDNA, binding approximately 2-fold tighter compared to ssDNA or G4. These findings support a model in which BRCA1 uses modular DNA binding domains to recognize diverse repair targets; DBD2 serves as a primary anchor to associate with a broad range of DNA structures with BRCT contributing to the contacts. DBD1 acts as the determinant of DNA structure-specific localization that may help direct BRCA1 to DSB sites during HR or to noncanonical elements such as chromatin and telomeres. These insights lay the groundwork for future studies examining how cancer-associated variants affect the DNA binding and repair phenotypes of BRCA1 and may inform the interpretation of variants of unknown clinical significance.},
}

@article {pmid40901206,
year = {2025},
author = {Luo, S and Chai, J and Cai, Y and Ding, L and Tang, S},
title = {Causality between telomere length and breast diseases: a two-sample bidirectional Mendelian randomization study.},
journal = {Annals of medicine and surgery (2012)},
volume = {87},
number = {9},
pages = {5551-5556},
pmid = {40901206},
issn = {2049-0801},
abstract = {BACKGROUND: The relationship between telomere length and breast diseases remains unclear, with conflicting evidence for breast cancer. Using an innovative genetic approach, we were the first to comprehensively assess their bidirectional causal relationship.

METHODS: Telomere length, breast cancer, benign neoplasm of breast, and breast inflammation were extracted from the genome-wide Association study (GWAS) database as the basis for large-scale population studies. The interaction of telomere length and breast diseases as exposure and outcome factors was analyzed by Mendelian randomization (MR).

RESULTS: When telomere length was used as an exposure factor and breast diseases as an outcome, the P value of MR was less than 0.05. Breast cancer (odds ratio (OR) = 1.130, 95% confidence interval (CI) = 1.047-1.219, P = 0.0016), benign neoplasm of breast (OR = 1.002, 95%CI = 1.001-1.004, P = 0.0007) and breast inflammation (OR = 1.487, 95%CI = 1.008-2.191, P = 0.0453). When breast diseases were taken as an exposure factor and telomere length was taken as an outcome, the P value of MR between breast cancer, benign neoplasm of breast, and telomere length was greater than 0.05, and breast inflammation could not be calculated by MR.

CONCLUSION: Telomere length is a risk factor for breast diseases, and longer telomeres increase the risk of breast cancer, benign neoplasm of breast, and breast inflammation. However, the reverse study showed no causal association between breast cancer, benign neoplasm of breast and telomere length, and the causal association between breast inflammation and telomere length was not clear. Moreover, further studies are needed to validate our findings in non-European populations.},
}

@article {pmid40900359,
year = {2025},
author = {Jaiswal, RK and Garibo Domingo, T and Grunchec, H and Singh, K and Pirooznia, M and Elhaik, E and Cohn, M},
title = {Subtelomeric elements provide stability to short telomeres in telomerase-negative cells of the budding yeast Naumovozyma castellii.},
journal = {Current genetics},
volume = {71},
number = {1},
pages = {19},
pmid = {40900359},
issn = {1432-0983},
mesh = {*Telomerase/genetics/metabolism ; *Telomere/genetics ; *Saccharomycetales/genetics ; *Telomere Homeostasis/genetics ; Telomere-Binding Proteins/genetics/metabolism ; *Telomere Shortening/genetics ; },
abstract = {Telomerase plays an important role in sustaining eukaryotic linear chromosomes, as elongation of telomeres is needed to counterbalance the shortening occurring in each replication round. Nevertheless, in telomerase-deficient cells, Alternative Lengthening of Telomeres (ALT) pathways can maintain telomeres by employing recombination-based mechanisms. In the budding yeast Naumovozyma castellii, effective activation of the ALT pathway leads to bypass of senescence and supports long-term growth. We found that telomere structures in N. castellii ALT cells are stably maintained at a shortened uniform length over extensive numbers of generations. This is correlated to the spreading of a subtelomeric sequence, TelKO element, to all telomeres. Genome sequencing of the wild-type strain revealed variants of the TelKO element, differing in their lengths, and separate ALT strains are maintained by spreading of distinct TelKO element variants. Although short uniform telomere structures are predominant, sporadic telomere lengthening events occur by addition of long repeated arrays of TelKO elements. The telomere-binding protein Rap1 can bind to TelKO sequences in vitro, indicating a functional role of TelKO elements in providing stability to shortened ALT telomeres. Our results suggest that stable maintenance and telomere functionality may be achieved by incorporating the distal subtelomeric TelKO sequences into the telomeric chromatin cap.},
}

*Telomerase/genetics/metabolism
*Telomere/genetics
*Saccharomycetales/genetics
*Telomere Homeostasis/genetics
Telomere-Binding Proteins/genetics/metabolism
*Telomere Shortening/genetics

@article {pmid40894009,
year = {2025},
author = {Jain, N and Luo, J and Yang, Y and Aschebrook-Kilfoy, B and Ahsan, H and Chen, L and Pierce, B},
title = {Determinants of chromosome-specific telomere lengths among 2,573 All of Us participants.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7293781/v1},
pmid = {40894009},
issn = {2693-5015},
abstract = {Telomeres are DNA-protein structures that protect chromosome ends. The DNA component of telomeres shortens as cells divide, and telomere length (TL) is a key biomarker of aging and disease risk. Most previous studies in humans of TL have analyzed average TL; thus, our knowledge of TL variability across chromosome arms remains limited. The availability of long-read whole-genome sequencing (lrWGS) data has enabled the development of computational methods to measure chromosome-specific TL (csTL). We generated lrWGS-based csTLs for > 2,500 All of Us participants and characterized variability in csTL attributable to individuals, chromosome arms, participant characteristics, and technical factors. We found that TL varies by chromosome arm (9.1% of the variance in csTL), mirroring patterns observed in prior studies and highlighting the potential for chromosome-specific mechanisms of TL regulation. Substantial variance in csTL (8.9%) was attributable to individual, independent of age, supporting the hypothesis that individuals are endowed with short or long TL in early development, which is maintained throughout life. While age is inversely associated with TL across all arms, the strength of the association varied, with longer arms showing stronger associations. We demonstrate that csTL estimates can be used to estimate disease associations at individual telomeres, including outlying values in the csTL distribution. Our work identifies lrWGS quality metrics that impact csTL estimation, providing a framework to guide future studies. This study demonstrates the utility of lrWGS data for csTL profiling in population cohorts. Larger studies of csTL are needed to advance our understanding of telomeres in aging and disease.},
}

@article {pmid40893773,
year = {2025},
author = {Bansal, A and Phogat, P and Kukreti, S},
title = {Na[+] selective structural switch from an intramolecular triplex to tetrad stabilised by non-canonical mispairs in double repeat of Arabidopsis thaliana telomere (T3AG3)2.},
journal = {Biochemistry and biophysics reports},
volume = {43},
number = {},
pages = {102203},
pmid = {40893773},
issn = {2405-5808},
abstract = {DNA is polymorphic, as with four nucleobases, it can be configured in a number of secondary structures. The four-stranded DNA structures consisting of G-tetrads have especially been intriguing because of their proven existence in human cells. Due to the high prevalence of putative G-quadruplex-forming sequence motifs in the human genome, scientists in recent years have highlighted the potential of exploiting these exotic structures for targeted therapies for various cancers. G-quadruplexes are the most common and well-studied arrangements of four guanines; however, other possible non-canonical arrangements of nucleobases have also been reported. Herein, using Gel electrophoresis, Circular Dichroism, UV & CD-thermal denaturation methods, and NMR, we suggested that a double repeat of Arabidopsis thaliana telomere (T3AG3)2 shows a structural switch from a non-canonical intramolecular triplex to a non-conventional tetrad other than an antiparallel G-quadruplex. This transition is mediated by increasing Na[+] cation concentration from 0.1 M to 1.0 M, and the tetrad is fairly stabilised by a hydrogen-bonded cyclic array of non-canonical/mismatch base pairs (G∗G, G∗T, and T∗T). Intriguingly, such a structural transition was not manifested in the presence of K[+] ions. To the best of our knowledge, such a cation-specific non-canonical structural switch, in a telomeric sequence, has not been proposed to date.},
}

@article {pmid40891961,
year = {2025},
author = {Nasiri, L and Vaez-Mahdavi, MR and Ghazanfari, T and Hassanpour, H and Kaboudanian-Ardestani, S},
title = {Expression of telomere length and shelterin genes in men and women leukocytes and their correlations with lipid peroxidation in sulfur mustard gas intoxication.},
journal = {Drug and chemical toxicology},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/01480545.2025.2553203},
pmid = {40891961},
issn = {1525-6014},
abstract = {Sulfur mustard (SM), a chemical warfare agent, inflicts severe acute and chronic health effects. This study investigates the impact of SM-induced oxidative stress on telomere length (TL) and shelterin gene expression, which are crucial for telomere maintenance in exposed veterans. This study involved SM-exposed veterans and non-exposed controls. The SM-exposed group was divided into three subgroups based on exposure severity (severe, mild, and asymptomatic) and gender. Leukocyte TL, transcript of shelterin genes (TPP1, POT1, TIN2, TRF1, TRF2, RAP1), and plasma MDA were measured. TL was decreased in the SM-exposed group compared to the non-exposed group, while the MDA level was increased. The SM-exposed group showed lower expression of TIN2, TRF2, and the composite shelterin genes compared to the control group. In the SM-exposed subgroups, TL, TRF2 transcript, and composite shelterin gene expression were reduced compared to the non-exposed group, while the MDA levels were significantly increased. There are negative correlations between MDA and both TIN2/TRF2 expression and TL, and positive correlations between TL and composite shelterin gene expression. In the gender comparison, there were different effects of SM toxicity on TIN2, TPP1, TRF2, and the composite of shelterin gene expression between SM-exposed men and women. SM-exposed men had significantly higher MDA levels, while women showed no significant change. Also, there was no difference between non-exposed men and women. It is concluded that SM exposure increases lipid peroxidation, shortens telomeres, and alters shelterin genes in a gender-specific manner, suggesting accelerated biological aging as a delayed toxic effect.},
}

@article {pmid40884660,
year = {2025},
author = {M'kacher, R and Colicchio, B and Junker, S and Schabat, S and Belaiba, R and Sontos, L and Heidingsfelder, L and Najar, W and Plesch, A and Voisin, P and Dieterlen, A and Jeandidier, E and Carde, P},
title = {DNA Damage, Telomere and Centromere Dysfunction in Chromothripsis Rearrangements.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {2968},
number = {},
pages = {441-455},
pmid = {40884660},
issn = {1940-6029},
mesh = {Humans ; *Chromothripsis ; *Telomere/genetics/metabolism ; *Centromere/genetics/metabolism ; *DNA Damage ; Neoplasms/genetics ; Chromosomal Instability ; Genomic Instability ; },
abstract = {The analysis of the origin of chromothripsis, catastrophic chromosomal rearrangements, has provided exceptional insights into various aspects of tumor progression and genetic disorders. Findings in chromothripsis have not only enhanced our understanding of genomic instability mechanisms, but also reshaped our views on chromosome mechanics. To date, the major mechanisms of chromothripsis described involve the incorporation of micronuclei into the primary nucleus and telomere crisis through the formation of dicentric chromosomes. Here, we reevaluated the impact of telomere and centromere sequences in the formation of micronuclei and anaphase bridges in cancer patients using our high throughput technique for the detection of telomere and centromere dysfunction and chromosomal instability biomarkers. We also discuss the emerging potential of exploiting telomere and centromere dysfunction combined with DNA damage as prognostic biomarkers and tools for personalized patient management.},
}

Humans
*Chromothripsis
*Telomere/genetics/metabolism
*Centromere/genetics/metabolism
*DNA Damage
Neoplasms/genetics
Chromosomal Instability
Genomic Instability

@article {pmid40879844,
year = {2025},
author = {Zhao, X and Shi, Y and Tang, M},
title = {Exploring the mediating role of telomere length in the association between physical activity and bone mineral density.},
journal = {Aging clinical and experimental research},
volume = {37},
number = {1},
pages = {263},
pmid = {40879844},
issn = {1720-8319},
mesh = {Humans ; *Bone Density/genetics/physiology ; *Exercise/physiology ; Female ; Middle Aged ; Male ; Aged ; *Telomere ; *Telomere Shortening ; Nutrition Surveys ; Osteoporosis/genetics ; DNA Methylation ; Telomere Homeostasis ; },
abstract = {BACKGROUND: Physical activity may mitigate osteoporosis progression by modulating telomere shortening processes.

AIMS: To explore the mediating role of telomere length (TL) in the relationship between physical activity and bone mineral density (BMD).

METHODS: This study enrolled 2,394 participants aged 50 years and older from the U.S. National Health and Nutrition examination Surveys. TL was measured by quantitative polymerase chain reaction (qPCR) method (TeloMean) and DNA methylation data (HorvathTelo), and accelerated telomere attrition was assessed through residual-based indices of TeloMeanAccel and HorvathTeloAccel. Physical activity was assessed via questionnaire and BMD was measured at multiple body sites. Multiple linear regression models were utilized to evaluate associations between TL metrics, physical activity, and BMD. Mediation analysis, restrict cubic spline (RCS) modeling, subgroup analyses and sensitivity analyses were further conducted.

RESULTS: After adjusting for covariates, TL metrics of TeloMean and HorvathTelo were found significantly positive correlations with BMD. HorvathTeloAccel, reflecting accelerated telomere shortening, also exhibited significant association with BMD. Physical activity demonstrated a significant positive association with total BMD (β = 0.046, 95%CI: 0.004-0.088). Mediation analysis revealed that TeloMean and HorvathTelo accounted for 4.78% and 20.86% of the total effect of physical activity on BMD, respectively, while HorvathTeloAccel explained 5.24% of the observed association.

CONCLUSION: Reduced physical activity and accelerated telomere attrition were related with BMD decline, and TL partially mediated the association. These findings suggest that enhancing physical activity could mitigate telomere shortening and promote bone health.},
}

Humans
*Bone Density/genetics/physiology
*Exercise/physiology
Female
Middle Aged
Male
Aged
*Telomere
*Telomere Shortening
Nutrition Surveys
Osteoporosis/genetics
DNA Methylation
Telomere Homeostasis

@article {pmid40880134,
year = {2025},
author = {Yuan, J and Li, J and Yong, J and Liao, X and Guo, H and Niu, Y},
title = {A telomere-to-telomere genome assembly of koi carp (Cyprinus carpio) using long reads and Hi-C technology.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
pmid = {40880134},
issn = {2047-217X},
support = {//Suxin Koi Farm/ ; },
mesh = {*Carps/genetics ; Animals ; *Genome ; *Telomere/genetics ; Genomics/methods ; Molecular Sequence Annotation ; },
abstract = {BACKGROUND: The common carp (Cyprinus carpio) is a key species in global freshwater aquaculture. One of its variants, the koi carp, is particularly prized for its aesthetic appeal. However, lacking a high-quality genome has limited genetic research and breeding efforts for common carp and koi carp.

FINDINGS: This study presents a gap-free genome for the Taisho Sansyoku koi carp strain (C. carpio). The assembly achieved a total size of 1,555.86 Mb with a contig N50 of 30.45 Mb, comprising 50 gap-free pseudochromosomes ranging in length from 20.70 to 49.02 Mb. The BUSCO completeness score reached 99.20%, and the Genome Continuity Inspector score was 85.82, indicating high genome integrity and accuracy. Notably, 83 out of 100 telomeres were detected, resulting in 33 chromosomes possessing complete telomeres. Comparative genomic analysis showed that the expanded gene families and unique genes play essential roles in various biological traits, such as energy metabolism, endocrine regulation, cell proliferation, and immune response, potentially related to multiple metabolic diseases and health conditions. The positively selected genes are linked to various biological processes, such as the metalloendopeptidase activity, which plays a significant role in the central nervous system and is associated with diseases.

CONCLUSIONS: The koi carp genome assembly (CC 4.0) fills a critical gap in understanding common carp's biology and adaptation. It provides an invaluable resource for molecular-guided breeding and genetic enhancement strategies, underscoring the importance of common carp and koi carp in aquaculture and ecological research.},
}

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

@article {pmid40878745,
year = {2025},
author = {Li, W and Liang, H and Sun, J and Zhang, X and He, Q and Zhou, P and Huo, D},
title = {A Near Telomere-To-Telomere Genome Assembly and Graph-Based Pangenome of Tartary Buckwheat (Fagopyrum tataricum).},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70333},
pmid = {40878745},
issn = {1467-7652},
support = {2023ZD04076//Biological Breeding-National Science and Technology Major Project/ ; TYSGJ202201//Critical Talent Workstation Project/ ; 202203021222244//Basic Research Program of Shanxi Province/ ; },
}

@article {pmid40877435,
year = {2025},
author = {McLoughlin, MA and Cheloor Kovilakam, S and Dunn, WG and Gu, M and Tobin, J and Pershad, Y and Williams, N and Leongamornlert, D and Dawson, K and Bond, L and Marando, L and Wen, S and Wilson, R and Valenzano, G and Symeonidou, V and Rak, J and Damaskou, A and Gozdecka, M and Liu, X and Barcena, C and Nomdedeu, J and Costeas, P and Dimitriou, ID and Fiorillo, E and Orrù, V and de Almeida, JG and McKerrell, T and Cullen, M and Mohorianu, I and Foukaneli, T and Warren, AJ and Wong, C and Follows, G and Godfrey, AL and Gudgin, E and Cucca, F and McKinney, E and Baxter, EJ and Gerstung, M and Mitchell, J and Wiseman, D and Bick, AG and Fabre, M and Quiros, PM and Nangalia, J and Kar, S and Vassiliou, GS},
title = {Telomere attrition becomes an instrument for clonal selection in aging hematopoiesis and leukemogenesis.},
journal = {Nature genetics},
volume = {},
number = {},
pages = {},
pmid = {40877435},
issn = {1546-1718},
support = {102160/B/13/Z//Wellcome Trust (Wellcome)/ ; CTRQQR-2021\100012//Cancer Research UK (CRUK)/ ; },
abstract = {The mechanisms through which mutations in splicing factor genes drive clonal hematopoiesis (CH) and myeloid malignancies, and their close association with advanced age, remain poorly understood. Here we show that telomere maintenance plays an important role in this phenomenon. First, by studying 454,098 UK Biobank participants, we find that, unlike most CH subtypes, splicing-factor-mutant CH is more common in those with shorter genetically predicted telomeres, as is CH with mutations in PPM1D and the TERT gene promoter. We go on to show that telomere attrition becomes an instrument for clonal selection in advanced age, with splicing factor mutations 'rescuing' HSCs from critical telomere shortening. Our findings expose the lifelong influence of telomere maintenance on hematopoiesis and identify a potential shared mechanism through which different splicing factor mutations drive leukemogenesis. Understanding the mechanistic basis of these observations can open new therapeutic avenues against splicing-factor-mutant CH and hematological or other cancers.},
}

@article {pmid40877081,
year = {2025},
author = {Karimi, B and Nabizadeh Nodehi, R and Yunesian, M},
title = {Retraction notice to "Serum level of PCBs and OCPs and leukocyte telomere length among adults in Tehran, Iran" [Chemosphere 248, June 2020, 126092].},
journal = {Chemosphere},
volume = {},
number = {},
pages = {144635},
doi = {10.1016/j.chemosphere.2025.144635},
pmid = {40877081},
issn = {1879-1298},
}

@article {pmid40872982,
year = {2025},
author = {Lim, J and Kim, J and Abdeahad, H and Hall, SA and Lesniewski, LA and Donato, AJ},
title = {Late-Life Aerobic Exercise Attenuates DNA Damage and Telomere Dysfunction in Non-Atheroprone but Not in Atheroprone Aortic Regions.},
journal = {Aging cell},
volume = {},
number = {},
pages = {e70196},
doi = {10.1111/acel.70196},
pmid = {40872982},
issn = {1474-9726},
support = {R01 AG060395/NH/NIH HHS/United States ; R01 AG048366/NH/NIH HHS/United States ; T32 HL007576/NH/NIH HHS/United States ; T32 HL139451/NH/NIH HHS/United States ; I01 BX004492/BX/BLRD VA/United States ; },
abstract = {Cellular senescence is a state of persistent cell cycle arrest and is a critical contributor to arterial aging. The primary drivers of cellular senescence are the DNA damage response (DDR) and telomere dysfunction, which is induced by increasing exposure to DNA-damaging stimuli such as atheroprone shear stress. While late-life aerobic exercise is an effective intervention to mitigate arterial aging, its specific impact on the DDR and telomere dysfunction is unknown and may not show uniform benefits across aortic regions subjected to atheroprone and non-atheroprone shear stress. This study investigates the influence of late-life aerobic exercise on DDR and telomere dysfunction in endothelial cells (EC) and vascular smooth muscle cells (VSMC) within the aortic regions exposed to distinct shear stress patterns. Old male C57BL6 mice were randomly assigned to a negative control (NC) group and habitual voluntary wheel running (VWR) groups for 16 weeks. The habitual VWR groups were further categorized into low (LR), moderate (MR), and high running (HR) groups based on their daily running distance throughout the intervention. EC and VSMC DDR and telomere dysfunction in NC, LR, and MR groups were comparable across the aortic regions. Interestingly, EC DDR and telomere dysfunction were mitigated in the non-atheroprone aortic regions in HR, but not in VSMC. These improvements were independent of telomere length. Collectively, these data provide evidence that late-life aerobic exercise selectively mitigates DDR and telomere dysfunction in ECs within non-atheroprone aortic regions, rather than atheroprone aortic regions, in an exercise volume-dependent manner, independent of telomere length.},
}

@article {pmid40870925,
year = {2025},
author = {Moustakli, E and Grigoriadis, T and Stavros, S and Potiris, A and Zikopoulos, A and Gerede, A and Tsimpoukis, I and Papageorgiou, C and Louis, K and Domali, E},
title = {Artificial Intelligence in Assessing Reproductive Aging: Role of Mitochondria, Oxidative Stress, and Telomere Biology.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {15},
number = {16},
pages = {},
pmid = {40870925},
issn = {2075-4418},
abstract = {Fertility potential ever more diminishes due to the complex, multifactorial, and still not entirely clarified process of reproductive aging in women and men. Gamete quality and reproductive lifespan are compromised by biologic factors like mitochondrial dysfunction, increased oxidative stress (OS), and incremental telomere shortening. Clinically confirmed biomarkers, including follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH), are used to estimate ovarian reserve and reproductive status, but these markers have limited predictive validity and an incomplete representation of the complexity of reproductive age. Recent advances in artificial intelligence (AI) have the capacity to address the integration and interpretation of disparate and complex sets of data, like imaging, molecular, and clinical, for consideration. AI methodologies that improve the accuracy of reproductive outcome predictions and permit the construction of personalized treatment programs are machine learning (ML) and deep learning. To promote fertility evaluations, here, as part of its critical discussion, the roles of mitochondria, OS, and telomere biology as latter-day biomarkers of reproductive aging are presented. We also address the current status of AI applications in reproductive medicine, promises for the future, and applications involving embryo selection, multi-omics set integration, and estimation of reproductive age. Finally, to ensure that AI technology is used ethically and responsibly for reproductive care, model explainability, heterogeneity of data, and other ethical issues remain as residual concerns.},
}

@article {pmid40868898,
year = {2025},
author = {Vakonaki, E and Vitiadou, MT and Panteris, E and Tzatzarakis, M and Tsatsakis, A and Hatzidaki, E},
title = {Maternal Lifestyle During Pregnancy and Its Influence on Offspring's Telomere Length.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
pmid = {40868898},
issn = {2075-1729},
abstract = {Telomeres are protective DNA sequences located at chromosome ends, essential to maintaining genomic stability. This narrative review examines how maternal lifestyle factors during pregnancy influence fetal telomere length (TL). Positive associations have been identified between offspring's TL and maternal consumption of nutrients such as vitamins C and D, folate, and magnesium. Additionally, adherence to a Mediterranean diet and regular physical activity during pregnancy are correlated with increased placental TL, supporting fetal genomic integrity. Conversely, maternal dietary patterns high in carbohydrates, fats, or alcohol, as well as exposure to triclosan and sleep-disordered breathing, negatively correlate with offspring's TL. Maternal infections may also shorten TL through heightened inflammation and oxidative stress. However, evidence regarding the impact of other lifestyle factors-including maternal stress, smoking, caffeine intake, polyunsaturated fatty acid consumption, obesity, and sleep quality-remains inconsistent. Given that shorter telomere length has been associated with cardiovascular, pulmonary, and neurodegenerative diseases, as well as certain types of cancer, these findings highlight the vital importance of maternal health during pregnancy in order to prevent potential adverse effects on the fetus. Further studies are required to elucidate the precise timing, intensity, and interplay of these influences, enabling targeted prenatal interventions to enhance offspring health outcomes.},
}

@article {pmid40868226,
year = {2025},
author = {Diaconu, M and Olaru, F and Abu-Awwad, A and Abu-Awwad, SA and Dragomir, T and Sacarin, G and Pilut, NC and Sorop, B and Bicu, M and Nitu, R},
title = {The Influence of Maternal Inflammatory Status on Fetal Telomere Length at Birth.},
journal = {Biomedicines},
volume = {13},
number = {8},
pages = {},
pmid = {40868226},
issn = {2227-9059},
support = {without a specific grant number//This research was funded by "Victor Babes" University of Medicine and Pharmacy, Timisoara/ ; },
abstract = {Background/Objectives: Fetal telomere length (FTL) at birth is considered a key marker of early biological aging and future disease risk. While chronic inflammation is known to accelerate telomere attrition in adults, limited evidence exists on how maternal inflammation during pregnancy impacts FTL. This study aimed to investigate the association between maternal systemic inflammatory status in late pregnancy and FTL at birth. Methods: We conducted a prospective cohort study including 150 clinically healthy pregnant women recruited in the third trimester. Participants were stratified post hoc into an inflammation group (n = 67) and a control group (n = 83) based on circulating inflammatory markers: high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), TNF-α, and IL-10. Umbilical cord blood was collected at birth, and telomere length was quantified using real-time PCR. Correlation and multivariable linear regression analyses were performed to evaluate associations between maternal inflammation and FTL. Results: Mothers in the inflammation group had significantly elevated hsCRP, IL-6, and TNF-α levels, and lower IL-10 concentrations. FTL was significantly shorter in this group compared to the controls. Unlike previous investigations that relied on single pro-inflammatory markers, our study tests a composite immune-balance index (IL-6/IL-10 ratio) together with hsCRP in a prospectively followed cohort of clinically healthy pregnancies. Using its correlation coefficient, the IL-6/IL-10 ratio alone explained approximately 28% of the total variance in fetal telomere length-almost double the variance captured by IL-6 assessed in isolation. IL-6 and hsCRP emerged as independent negative predictors of FTL in multivariable models (β = -0.37 and -0.29, respectively). The IL-6/IL-10 ratio showed the strongest inverse correlation with FTL (r = -0.53, p < 0.001). Conclusions: Subclinical systemic inflammation in late pregnancy is independently associated with shorter fetal telomere length at birth, highlighting maternal immune imbalance (especially IL-6/IL-10 ratio) as a modifiable determinant of early biological aging. These findings underscore the need to consider maternal inflammatory profiling in pregnancy as a potential target for early-life preventive strategies.},
}

@article {pmid40867830,
year = {2025},
author = {Valeanu, A and Margina, D and Moreno-Villanueva, M and Blasco, M and Sikora, E and Mosieniak, G and Capri, M and Breusing, N and Bernhardt, J and Schön, C and Toussaint, O and Debacq-Chainiaux, F and Grubeck-Loebenstein, B and Weinberger, B and Fiegl, S and Gonos, ES and Hervonen, A and Slagboom, EP and de Craen, A and Dollé, MET and Jansen, EHJM and Mocchegiani, E and Giacconi, R and Piacenza, F and Malavolta, M and Weber, D and Stuetz, W and Grune, T and Franceschi, C and Bürkle, A and Gradinaru, D},
title = {Causal Inference Approaches Reveal Associations Between LDL Oxidation, NO Metabolism, Telomere Length and DNA Integrity Within the MARK-AGE Study.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/antiox14080933},
pmid = {40867830},
issn = {2076-3921},
abstract = {Genomic instability markers are important hallmarks of aging, as previously evidenced within the European study of biomarkers of human aging, MARK-AGE; however, establishing the specific metabolic determinants of vascular aging is challenging. The objective of the present study was to evaluate the impact of the susceptibility to oxidation of serum LDL particles (LDLox) and the plasma metabolization products of nitric oxide (NOx) on relevant genomic instability markers. The analysis was performed on a MARK-AGE cohort of 1326 subjects (635 men and 691 women, 35-75 years old) randomly recruited from the general population. The Inverse Probability of Treatment Weighting causal inference algorithm was implemented in order to assess the potential causal relationship between the LDLox and NOx octile-based thresholds and three genomic instability markers measured in mononuclear leukocytes: the percentage of telomeres shorter than 3 kb, the initial DNA integrity, and the DNA damage after irradiation with 3.8 Gy. The results showed statistically significant telomere shortening for LDLox, while NOx yielded a significant impact on DNA integrity. Overall, the effect on the genomic instability markers was higher than for the confirmed vascular aging determinants, such as low HDL cholesterol levels, indicating a meaningful impact even for small changes in LDLox and NOx values.},
}

@article {pmid40867046,
year = {2025},
author = {Smoom, R and Lichtental, D and Kaestner, KH and Tzfati, Y},
title = {The house mouse maintains constant telomere length throughout life.},
journal = {Nucleic acids research},
volume = {53},
number = {16},
pages = {},
doi = {10.1093/nar/gkaf830},
pmid = {40867046},
issn = {1362-4962},
support = {2071/18//Israel Science Foundation/ ; 1342/23//Israel Science Foundation/ ; R37-DK053839/DK/NIDDK NIH HHS/United States ; R01-CA249929/DK/NIDDK NIH HHS/United States ; //Israel-UK-Palestine GROWTH Fellowship/ ; 1342/23//ISF/ ; },
mesh = {Animals ; Mice ; *Telomere Homeostasis/genetics ; *Telomere/genetics/metabolism ; *Aging/genetics ; Telomerase/metabolism/genetics ; Male ; Telomere Shortening ; Leukocytes/metabolism ; Female ; },
abstract = {Telomeres protect the chromosome ends from deleterious DNA damage response and repair activities. In humans, telomerase maintains telomere length in germ and stem cells, but not in most somatic cells. Consequently, telomeres shorten with cell division and age, limiting cell proliferation and protecting against cancer. When telomeres become critically short, they may also cause senescence, inflammation, and organ failure, which are major drivers of aging. Therefore, maintaining an optimal, age-appropriate telomere length is crucial for healthy aging. In the house mouse, Mus musculus, telomerase is active in most somatic tissues, yet its long telomeres were thought to shorten rapidly with age. We have followed telomere length over age in blood and tail of wild-type M. musculus and in two engineered mouse strains with shorter telomeres (Telomouse and HHS mouse). We also measured the precise length of single telomeres in blood leukocytes of these mouse strains by a long-read nanopore sequencing method, NanoTelSeq. We show that telomeres in blood and tail of these three mouse strains do not shorten with age. We conclude that M. musculus maintains long telomeres in blood and tail throughout life, excluding the possibility that global telomere shortening in these tissues contribute to aging-associated phenotypes.},
}

Animals
Mice
*Telomere Homeostasis/genetics
*Telomere/genetics/metabolism
*Aging/genetics
Telomerase/metabolism/genetics
Male
Telomere Shortening
Leukocytes/metabolism
Female

@article {pmid40866587,
year = {2025},
author = {DePinho, RA},
title = {Telescopes, telomeres and turning points.},
journal = {Nature cancer},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43018-025-01024-y},
pmid = {40866587},
issn = {2662-1347},
}

@article {pmid40862088,
year = {2025},
author = {Bhatt, SP and Pandey, S and Misra, A},
title = {Independent Effects of Vitamin D on Leukocyte Telomere Length and Activity: An RCT in Asian Indian Women With Prediabetes.},
journal = {Journal of the Endocrine Society},
volume = {9},
number = {9},
pages = {bvaf124},
pmid = {40862088},
issn = {2472-1972},
abstract = {INTRODUCTION: Prediabetes is increasing in India and progresses rapidly to type 2 diabetes. The impact of vitamin D3 supplementation on telomerase activity and leukocyte telomere length (LTL) among people with prediabetes has been poorly researched.

RESEARCH DESIGN AND METHODS: In this 18-month prospective trial, we enrolled 121 women with prediabetes and randomized them into intervention (vitamin D3 supplementation, n = 61) and placebo (n = 60) groups. LTL and telomerase activity were measured.

RESULTS: In the current study, LTL and telomerase activity were assessed at visit 1 (week 0), visit 2 (week 52), and visit 3 (week 78). LTL increased significantly in the intervention group by week 52 (P = .004) and became more pronounced at week 78 (P = .001), representing a 14.5% increase from baseline. Similarly, telomerase activity showed progressive enhancement with vitamin D treatment, achieving significance by week 52 (P = .001) and continuing through week 78 (P < .0001), reflecting a 16.2% increase from baseline. Within-group analysis confirmed significant improvements over time in the vitamin D group (P = .002) but not in placebo (P = .18) group. After adjusting for potential confounders including body mass index, subscapular skinfold thickness, fasting blood glucose, and PTH, serum 25-hydroxyvitamin D levels maintained a significant independent association with both LTL (OR = 2.053; 95% CI, 1.410-2.243; P = .001) and telomerase activity (OR = 2.032; 95% CI, 1.410-2.254; P = .001) in the intervention group.

CONCLUSION: Vitamin D supplementation, over 78 weeks, is independently associated with increased LTL and telomerase activity in Asian Indian women with prediabetes.},
}

@article {pmid40854872,
year = {2025},
author = {Güzel, N and Schumacher, Y and Kricheldorf, K and Vieri, M and Kirschner, M and Gerhard-le Gars, AC and Panse, J and Tometten, M and Walter, J and Gehrig, A and Kunstmann, E and Holthöfer, L and Schweiger, S and Wolff, D and Kraft, F and Elbracht, M and Kurth, I and Brümmendorf, TH and Meyer, R and Beier, F},
title = {Allogeneic stem cell transplantation from variant-carrying family donors leads to long-term engraftment in Telomere Biology Disorders.},
journal = {Blood cancer journal},
volume = {15},
number = {1},
pages = {142},
pmid = {40854872},
issn = {2044-5385},
}

@article {pmid40854256,
year = {2025},
author = {Musa, AA and Mamat-Hamidi, K and Idrus, Z and Chung, ELT and Samat, N and Kassim, NA},
title = {Effects of heat stress on growth metrics, carcass characteristics, telomere length, and gene expression in chickens.},
journal = {Poultry science},
volume = {104},
number = {11},
pages = {105698},
doi = {10.1016/j.psj.2025.105698},
pmid = {40854256},
issn = {1525-3171},
abstract = {This study investigated the impact of heat stress (HS) on growth performance, carcass traits, telomere length (TL), and gene expression profiles in three chicken breeds with varying growth rates: slow-growing (SAGA), medium-growing (Sasso), and fast-growing (Cobb 500). Three hundred 14-day-old male chicks were exposed to either control (25°C) or HS (34°C for 6 hours/day) conditions for four weeks in a controlled environment. Weekly growth metrics, TL at two and four weeks, Heat Shock Protein 70 (HSP70) and Insulin-Like Growth Factor-1 (IGF-1) expression in muscle and liver at two and four weeks of HS exposure, and carcass/organ yields at four weeks were analyzed. Cobb 500 chickens exhibited significant growth reductions under HS, while SAGA showed resilience. Notably, SAGA chickens exhibited a significant increase in intestinal organ mass under HS, which may indicate an adaptive response to thermal stress. HS exposure significantly shortened TL across all breeds, suggesting its utility as a universal biomarker for HS in chickens. All breeds upregulated HSP70 expression, with the Cobb 500 showing the most prominent increase. Similarly, IGF-1 was expressed (upregulated), particularly in 500 broilers at both time-points, highlighting breed-specific differences in growth performance. These results demonstrate breed-specific physiological adaptations to HS. TL and stress-related gene expression are crucial indicators of heat susceptibility and adaptation. The study provides insights into developing breed-specific management and breeding strategies to enhance poultry resilience to increasing global temperatures.},
}

@article {pmid40851308,
year = {2025},
author = {Huang, SB and Wu, J and Xu, ZJ and Mo, WT and Yuan, S and Jiang, XY and Wang, HF and Xie, L},
title = {TeloComp: an efficient toolkit for accurate assembly of the telomeres in T2T genome.},
journal = {Plant communications},
volume = {},
number = {},
pages = {101492},
doi = {10.1016/j.xplc.2025.101492},
pmid = {40851308},
issn = {2590-3462},
}

@article {pmid40849907,
year = {2025},
author = {Janovič, T and Perez, GI and Boelting, G and Schmidt, JC},
title = {TRF1 and TRF2 form distinct shelterin subcomplexes at telomeres.},
journal = {Cell reports},
volume = {44},
number = {9},
pages = {116178},
doi = {10.1016/j.celrep.2025.116178},
pmid = {40849907},
issn = {2211-1247},
abstract = {The shelterin complex protects chromosome ends from aberrant DNA repair and regulates telomerase access to telomeres. Shelterin is composed of six proteins (TRF1, TRF2, TIN2, TPP1, POT1, and RAP1) that can assemble into various subcomplexes in vitro, but their stoichiometry and dynamics in cells remain poorly understood. To quantitatively analyze shelterin function, we generated a panel of human cancer cell lines expressing HaloTagged shelterin proteins from their endogenous loci. We determined both the total and telomeric abundance of each subunit, demonstrating that shelterin proteins are present at telomeres in equal numbers. Using single-molecule live-cell imaging, we showed that TRF1-TIN2-TPP1-POT1 and TRF2-RAP1 form distinct subcomplexes that bind non-overlapping sites on telomeric chromatin. TRF1-TIN2-TPP1-POT1 tightly associates with telomeres, whereas TRF2-RAP1 binds more dynamically, facilitating the recruitment of co-factors that protect chromosome ends. Altogether, our work provides mechanistic insight into shelterin function in telomere maintenance and advances our understanding of telomeric chromatin architecture.},
}

@article {pmid40849514,
year = {2025},
author = {Li, D and Li, W and Liao, X and Jiang, S and Ma, M and Hu, Z and Lin, K and Yu, W and Sun, X and Fan, Y and Wu, H and Yin, M and Wang, L and Suo, L and Long, H and Lu, X and Kuang, Y and Lyu, Q},
title = {NAD[+]-dependent Sirt6 is a key regulator involved in telomere shortening of in vitro-cultured preimplantation embryos.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1275},
pmid = {40849514},
issn = {2399-3642},
support = {23ZR1437500//Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)/ ; 81901478//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Sirtuins/metabolism/genetics ; Animals ; *Blastocyst/metabolism ; *Telomere Shortening ; Mice ; Female ; *NAD/metabolism/deficiency ; Mice, Knockout ; Embryo Culture Techniques ; Telomere/metabolism ; },
abstract = {Telomere length (TL) is important for maintaining the individual health of a species. Recent studies shows that in vitro fertilization therapy can drastically reduce TL in offspring, however, the underlying molecular mechanism remains unknown. Sirt6 is a NAD[+]-dependent epigenetic regulator that has recently been found to play an important role in maintaining telomere stability. Here, we report that NAD[+] deficiency in in vitro-cultured blastocysts impairs Sirt6 function, triggering telomere shortening of the inner cell mass and possibly affecting newborns. This phenotype could be effectively mitigated by supplementation with nicotinamide mononucleotide (NAD[+] precursor) during in vitro culture, while it could not be achieved in Sirt6 conditional knockout embryos. mtROS accumulation and epigenetic modifications may also be involved in this process. Our results reveal the mechanism by which in vitro culture induces telomere shortening in preimplantation embryos, providing a potential target for improving in vitro culture conditions.},
}

*Sirtuins/metabolism/genetics
Animals
*Blastocyst/metabolism
*Telomere Shortening
Mice
Female
*NAD/metabolism/deficiency
Mice, Knockout
Embryo Culture Techniques
Telomere/metabolism

@article {pmid40848782,
year = {2025},
author = {Shiburah, ME and de Oliveira, BCD and Bisetegn, H and de Oliveira, LS and Passos, AO and Silva, DA and Assis, LHC and Alves, CS and Ernst, E and Barreto, RM and Batista, MM and Soeiro, MNC and Menozzi, BD and Langoni, H and Aoki, JI and Coelho, AC and Miranda Junior, AS and Machado, CR and Cano, MIN},
title = {The absence of the Leishmania major telomerase TERT component links telomeres and cell homeostasis with infectivity.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {147036},
doi = {10.1016/j.ijbiomac.2025.147036},
pmid = {40848782},
issn = {1879-0003},
abstract = {We studied the impacts of deleting the telomerase reverse transcriptase component of the Leishmania major (LmTERT) telomerase complex. The Leishmania genus comprises species that cause leishmaniasis, a neglected disease that lacks effective treatment and control options, highlighting the need for alternative therapeutics. Telomerase plays a crucial role in maintaining the integrity of eukaryotic genomes by synthesizing telomeres through its TERT and telomerase RNA components. Here, we show that the absence of TERT in L. major has a pleiotropic effect on parasite homeostasis, causing growth and proliferation alterations, progressive telomere shortening, increased TERRA expression, and γH2A signaling, besides the early onset of autophagosomes and mitochondrial insults. The proteomic analysis of LmTERT knockout promastigotes compared with the parental lineage confirmed some of these alterations, showing an imbalance in constituents of chromatin, plasma membrane, mitochondria, and cytoskeleton, and the unexpected presence of proteins involved in autophagy and virulence at this parasite life stage. Inactivating LmTERT also impaired metacyclogenesis, abolishing the parasite's infectivity. These results establish a strong link between telomeres, cell homeostasis, and the parasite's infective capability, highlighting LmTERT as a promising target for antiparasitic strategies.},
}

@article {pmid40848099,
year = {2025},
author = {Adhikari, S and Yasmin, R and Bandyopadhyay, A and Nayek, K and Haldar, A and Ghosh, S and Mandal, P},
title = {Identification of molecular heterogeneity in telomere maintenance pathway of aplastic anemia.},
journal = {Molecular biology reports},
volume = {52},
number = {1},
pages = {843},
pmid = {40848099},
issn = {1573-4978},
support = {BT/PR18640/BIC/101/924/2016 DATED 20.09.2017//DBT-BIOCARE/ ; BT/PR18640/BIC/101/924/2016 DATED 20.09.2017//DBT-BIOCARE/ ; NTA Ref. No.: 201610124607 Dated 01.04.2021//CSIR-UGC/ ; ECR/2017/000595, Dated:16.07.2018//DST-SERB/ ; },
}

@article {pmid40847086,
year = {2025},
author = {Feng, Z and Li, J and Zhang, H and Liu, S and Wang, Y and Zhou, M and Ding, Z and Xiao, L},
title = {Obesity impact on leukocyte telomere shortening and immune aging assessed by Mendelian randomization and transcriptomics analysis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30983},
pmid = {40847086},
issn = {2045-2322},
support = {82103785 and 82273582//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Obesity/genetics/immunology ; Mendelian Randomization Analysis ; *Telomere Shortening/genetics ; Male ; Female ; Body Mass Index ; Middle Aged ; *Transcriptome ; *Leukocytes/metabolism ; Polymorphism, Single Nucleotide ; Adult ; *Leukocytes, Mononuclear/metabolism ; Gene Expression Profiling ; Cellular Senescence/genetics ; *Aging/genetics/immunology ; Waist-Hip Ratio ; Telomere/genetics ; },
abstract = {Obesity and aging are key research topics in contemporary biomedical science. While studies have explored the effects of obesity on various health indicators, the precise mechanisms through which obesity may affect leukocyte telomere length (LTL)-and whether this impact contributes to accelerated immune cell senescence-remain unclear and warrant further investigation. In this study, we employed single nucleotide polymorphisms (SNPs) associated with four obesity indices-body mass index (BMI), body fat percentage (BFP), waist circumference (WC), and waist-hip ratio (WHR)-as instrumental variables (IVs) to assess the causal relationship between these indices and LTL through Mendelian randomization (MR) analysis. Additionally, we analyzed transcriptome sequencing data from peripheral blood mononuclear cells (PBMCs) across three groups: lean individuals, individuals with obesity before undergoing bariatric surgery, and individuals with obesity after surgery, and focus on the expression changes of cellular senescence and telomere dynamics related genes in PBMCs of individuals with obesity before and after weight loss intervention. The results showed a negative causal relationship between BMI (B=-0.04, P < 0.0001), BFP (B=-0.06, P < 0.0001) and LTL without being impacted by lipid profiles and T2D. The negative causal relationship between WC (B=-0.04, P < 0.0001) and LTL may be dependent on lipid levels, but not on T2D. WHR had no significant causal relationship (P > 0.05). Transcriptomic analysis further revealed that individuals with obesity had higher expression of cellular senescence-related genes such as ID2, LMNA, and TENT4B in PBMCs compared to lean individuals, with expression levels of these genes significantly decreasing after bariatric surgery. These findings underscore the detrimental impact of obesity on telomere attrition and immune cell senescence, highlighting the potential benefits of obesity management for slowing the biological process of cellular and immune aging.},
}

Humans
*Obesity/genetics/immunology
Mendelian Randomization Analysis
*Telomere Shortening/genetics
Male
Female
Body Mass Index
Middle Aged
*Transcriptome
*Leukocytes/metabolism
Polymorphism, Single Nucleotide
Adult
*Leukocytes, Mononuclear/metabolism
Gene Expression Profiling
Cellular Senescence/genetics
*Aging/genetics/immunology
Waist-Hip Ratio
Telomere/genetics

@article {pmid40844718,
year = {2025},
author = {Oh, JH and Lee, HJ and Kim, W and Oh, DE and Kim, HK and Kim, EH and Choe, J and Jun, HR and Park, CW and Kang, YG and Kim, CJ and Sung, CO and Kim, TW},
title = {Whole genome sequencing reveals telomere associated genomic differences between healthy and unhealthy aging in a Korean population.},
journal = {Biogerontology},
volume = {26},
number = {5},
pages = {167},
pmid = {40844718},
issn = {1573-6768},
support = {2018IP0622 and 2019IF0590//Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea/ ; },
mesh = {Humans ; Middle Aged ; Aged ; Male ; *Telomere/genetics ; Female ; Whole Genome Sequencing ; *Aging/genetics ; Republic of Korea ; Case-Control Studies ; *Healthy Aging/genetics ; Genomic Instability ; Oxidative Stress/genetics ; DNA Repair/genetics ; Aged, 80 and over ; Telomere Homeostasis/genetics ; Telomere Shortening ; },
abstract = {One of the major challenges in modern biogerontology is understanding the accumulation of molecular damage and the manifestation of phenotypic heterogeneity during aging. Notably, genomic instability caused by impaired DNA damage repair along with telomere attrition are primary drivers of aging. However, how these aging-related characteristics differ in individuals who age healthily without developing major age-associated diseases remains unclear. Here, whole genome sequencing (WGS) was performed on 100 healthy agers (≥ 60 years old, no age-related diseases) and 100 unhealthy agers (≥ 60 years old, at least one age-related disease/condition) based on a case-control study. Telomere length was measured using TelSeq and Computel. High-functional impact germline variant (gHFI) burden and alteration pattern at the pathway level were also analyzed. The GTEx dataset including 751 individuals was used to observe the functional impact of identified germline variants at the molecular level. Telomere length showed minimal differences before 65 years of age but declined rapidly in unhealthy agers beyond this age. Additionally, healthy agers had lower gHFI burden, particularly in DNA repair genes such as BLM. Pathway analysis revealed enrichment of oxidative stress-related mutations in healthy agers, correlated with reduced oxidative stress and upregulated antioxidant enzymes (SOD1 and SOD2). Overall, genomic instability preserved through slow telomere attrition and reduced DNA repair defects plays a key role in healthy aging. Improved oxidative stress resistance may contribute to healthier aging, highlighting the role of genetic factors in reducing age-related decline and supporting overall well-being in later life.},
}

Humans
Middle Aged
Aged
Male
*Telomere/genetics
Female
Whole Genome Sequencing
*Aging/genetics
Republic of Korea
Case-Control Studies
*Healthy Aging/genetics
Genomic Instability
Oxidative Stress/genetics
DNA Repair/genetics
Aged, 80 and over
Telomere Homeostasis/genetics
Telomere Shortening

@article {pmid40841804,
year = {2025},
author = {Zhang, X and Chen, J and Zhou, W and Wen, J and Shi, Q},
title = {A telomere-to-telomere gap-free genome assembly of the protandrous hermaphrodite Asian seabass (Lates calcarifer).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1457},
pmid = {40841804},
issn = {2052-4463},
mesh = {Animals ; *Telomere ; *Bass/genetics ; *Genome ; Female ; Male ; *Hermaphroditic Organisms/genetics ; },
abstract = {As a protandrous hermaphroditic fish species with natural sex change from male to female, Asian seabass (Lates calcarifer) represents an attractive model for studying sequential hermaphroditism. In this study, we constructed the first telomere-to-telomere (T2T) gap-free genome assembly of Asian seabass, by integration of MGI short-read, PacBio HiFi long-read, ONT ultra-long and Hi-C sequencing technologies. The haplotypic 614.19 Mb genome sequences were successfully anchored onto 24 chromosomes, demonstrating exceptional contiguity with a contig N50 of 26.57 Mb. Comprehensive annotation revealed precise localization of telomeric repeats and centromeric regions across various chromosomes. Good results from Merqury (QV: 57.8), CRAQ (99.45%) and BUSCO (100%) indicate a high level of accuracy for the assembled genome. ONT ultra-long and PacBio HiFi sequencing data were aligned with the assembly using minimap2, resulting in a mapping rate over 98%. Repetitive elements accounted for 18.18% (111.64 Mb) of the entire genome, and a total of 25,093 protein-coding genes were annotated. This high-quality T2T genome assembly provides a valuable genetic resource for in-depth comparative genomics, population genetics, molecular breeding, and functional studies of this economically important marine species. This reference assembly also facilitates investigations into the detailed molecular mechanisms underlying its unique reproductive strategy of the protandrous hermaphrodite Asian seabass.},
}

Animals
*Telomere
*Bass/genetics
*Genome
Female
Male
*Hermaphroditic Organisms/genetics

@article {pmid40834628,
year = {2025},
author = {Rodríguez-Fernández, B and González-Escalante, A and Genius, P and E Evans, T and Ortiz-Romero, P and Minguillón, C and Kollmorgen, G and Ashton, NJ and Zetterberg, H and Blennow, K and Gispert, JD and Navarro, A and Suárez-Calvet, M and Sala-Vila, A and Crous-Bou, M and Vilor-Tejedor, N and , },
title = {Longitudinal association of shorter leukocyte telomere length with CSF biomarker dynamics across early Alzheimer's disease stages in at-risk individuals.},
journal = {EBioMedicine},
volume = {119},
number = {},
pages = {105886},
doi = {10.1016/j.ebiom.2025.105886},
pmid = {40834628},
issn = {2352-3964},
abstract = {BACKGROUND: Short telomere length (TL), a hallmark of biological ageing, has been associated with an increased risk of Alzheimer's disease (AD), but its pathophysiological role remains unclear. This study explored the relationship between blood leukocyte TL (LTL), cerebrospinal fluid (CSF) AD biomarkers changes, and brain structure across early stages of the AD continuum.

METHODS: We included 346 cognitively unimpaired participants (aged 49-71) from the ALFA cohort, enriched for AD risk (53.2% APOE-ε4 carriers; 34% amyloid-positive). LTL was measured at baseline (visit 0) using quantitative PCR. Associations were assessed between baseline LTL and CSF biomarkers at visit 1 (mean follow-up from baseline = 3.98 years, SD = 1.02), and with changes in CSF biomarkers between visits 1 and 2 (mean interval = 3.45 years, SD = 0.58). Cortical thickness in ageing- and AD-vulnerable brain regions was evaluated by magnetic resonance imaging (MRI) at visit 1. Analyses were stratified by APOE-ε4 status and amyloid-tau (AT) profiles. Mediation models tested whether CSF biomarkers mediated LTL-cortical thickness associations.

FINDINGS: Shorter LTL was associated with higher astrocytic reactivity at visit 1 and with increased synaptic dysfunction over time. Among APOE-ε4 carriers and AT-positive individuals, shorter LTL was associated with higher p-tau181 and neurodegeneration markers. Shorter LTL was associated with greater cortical thickness in ageing- and AD-vulnerable regions, partially mediated by astrocytic reactivity biomarkers.

INTERPRETATION: These findings suggest that shorter telomeres are associated with early AD-related biological changes, potentially via mechanisms involving astrocytic reactivity and brain structural alterations. LTL may serve as an early marker of vulnerability to neurodegenerative processes in at-risk populations.

FUNDING: AARG-19-618265; PI19/00119; LCF/PR/GN17/10300004; TriBEKa-17-519007; # SLT002/16/00201.},
}

@article {pmid40831801,
year = {2025},
author = {Vakonaki, E and Vitiadou, MT and Paraskevopoulou, NI and Tzatzarakis, M and Baliou, S and Ioannou, P and Alegakis, A and Lamprakis, T and Fragkiadaki, P and Mylonaki, E and Volonaki, Z and Anagnostatou, N and Makrygiannakis, F and Makrigiannakis, A and Spandidos, DA and Tsatsakis, A and Hatzidaki, E},
title = {Correlation of telomere length between full and preterm neonates and their mothers.},
journal = {Experimental and therapeutic medicine},
volume = {30},
number = {4},
pages = {187},
pmid = {40831801},
issn = {1792-1015},
abstract = {Telomeres are nucleoprotein complexes that serve as protective caps from the DNA damage response at the ends of chromosomes. During aging, telomeres gradually shorten, and genomic instability arises through the induction of senescence. The present study aimed to elucidate the association between maternal characteristics, their medical history and pregnancy details with the telomere length (TL) of neonates. Blood samples were collected from 54 mothers and their neonates, and DNA extraction and measurement of TL was performed by quantitavive PCR. The results showed that maternal TL was negatively correlated with body mass index before pregnancy. A weak to moderate significant correlation was observed between maternal and neonatal TL. Non-significant differences were found between the maternal TL and their smoking habits, as well as medical and gestation history.},
}

@article {pmid40829179,
year = {2025},
author = {Monroe, TO},
title = {Genetic risk in telomere biology disorders: it adds up.},
journal = {The Journal of clinical investigation},
volume = {135},
number = {16},
pages = {},
pmid = {40829179},
issn = {1558-8238},
mesh = {Humans ; *Telomere/genetics/pathology ; Genetic Predisposition to Disease ; *Telomere Homeostasis/genetics ; Genetic Variation ; Penetrance ; Risk Factors ; },
abstract = {For many conditions, genotyping aids in clinical decision making. However, interpreting the clinical significance of genetic variants remains challenging, in part because a single risk variant does not always lead to disease, and variant carriers experience variable outcomes. One hypothesis underlying these phenomena, which are known as incomplete penetrance and variable expressivity, respectively, is that additional common genetic variation beyond the primary variant influences the presence and severity of disease. In this issue of JCI, Poeschla et al. present a compelling argument that common variants linked to telomere length act together with high-risk telomere biology disorder variants to scale outcomes. These data support a model in which many variants interact to shape cumulative risk.},
}

Humans
*Telomere/genetics/pathology
Genetic Predisposition to Disease
*Telomere Homeostasis/genetics
Genetic Variation
Penetrance
Risk Factors

@article {pmid40826164,
year = {2025},
author = {Ismail, A and Jaalouk, K and Koteish, J and Tarhini, Y and Sadier, NS and Abou-Abbas, L},
title = {Correction: Exploring the association between depression and telomere length: A systematic review and meta-analysis.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30230},
doi = {10.1038/s41598-025-15646-w},
pmid = {40826164},
issn = {2045-2322},
}

@article {pmid40826141,
year = {2025},
author = {Hill, C and Smyth, L and Kilner, J and Quinn, K and Scott, A and Neville, C and Kee, F and McGuinness, B and McKnight, AJ},
title = {Telomere length measures in the Northern Ireland cohort for the longitudinal study of ageing (NICOLA).},
journal = {BMC research notes},
volume = {18},
number = {1},
pages = {359},
pmid = {40826141},
issn = {1756-0500},
support = {PF2502\5//Vivensa Foundation/ ; R01AG068937/AG/NIA NIH HHS/United States ; R01AG068937/AG/NIA NIH HHS/United States ; R01AG068937/AG/NIA NIH HHS/United States ; STL/5569/19//HSC R&D division/ ; STL/5569/19//HSC R&D division/ ; STL/5569/19//HSC R&D division/ ; MRC MC_PC_20026//UKRI MRC/ ; MRC MC_PC_20026//UKRI MRC/ ; MRC MC_PC_20026//UKRI MRC/ ; ES/L0084559/1//The Atlantic Philanthropies, the Economic and Social Research Council/ ; ES/L0084559/1//The Atlantic Philanthropies, the Economic and Social Research Council/ ; ES/L0084559/1//The Atlantic Philanthropies, the Economic and Social Research Council/ ; STL/4717/12//the Health and Social Care Research and Development Division of the Public Health Agency/ ; STL/4717/12//the Health and Social Care Research and Development Division of the Public Health Agency/ ; STL/4717/12//the Health and Social Care Research and Development Division of the Public Health Agency/ ; },
abstract = {OBJECTIVES: Using blood derived DNA collected from individuals within the Northern Ireland COhort for the Longitudinal study of Ageing (NICOLA), quantitative real-time polymerase chain reaction (RT-PCR) based absolute telomere length measures were derived in triplicate. This data is generated on a subset of participants (n = 2,971) within the NICOLA cohort at Wave 1 baseline. NICOLA commenced Wave 3 of data collection in Autumn 2024.

DATA DESCRIPTION: The NICOLA study recruited approximately 8,500 people from across Northern Ireland, with individuals recruited as representative of the Northern Ireland population. At recruitment, the NICOLA cohort was 45% male and 55% female. Adults were recruited over the age of 50, with approximately 50% of participants aged between 50 and 65, and 10% of participants over the age of 80. Telomere length (TL) values were determined for 2,971individuals (47.7% male) across 33 batches using the Absolute Human Telomere Length Quantification qPCR Assay kit and Roche LightCycler 480 II. Within-batch duplicate measures were established, as were water controls and non-template controls.},
}

@article {pmid40825835,
year = {2025},
author = {Chung, YP and Chung, WS},
title = {Telomere shortening in middle-aged and elderly individuals with varying severities of obstructive sleep apnea.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {30277},
pmid = {40825835},
issn = {2045-2322},
abstract = {Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airway obstruction during sleep and leads to oxidative stress, systemic inflammation, and potentially accelerated telomere shortening. Studies comparing telomere length (TL) in individuals with and without OSA have obtained inconsistent results. This study compared TL across individuals without and with OSA of varying severity. We recruited 103 participants from a sleep clinic, all of whom underwent in-laboratory polysomnography and TL measurement. To assess TL, quantitative PCR was conducted for genomic DNA extracted from peripheral blood samples. Four participants were excluded because of sleep durations of < 4 h during polysomnography. The final analysis included 99 individuals (46 men and 53 women). Among these individuals, 13 did not have OSA; 28, 24, and 34 had mild OSA, moderate OSA, and severe OSA, respectively. Telomeres were significantly longer in individuals without OSA than in individuals with mild, moderate, and severe OSA (8.4 ± 5.1 kb, 5.7 ± 3.1 kb, 5.7 ± 2.2 kb, and 4.8 ± 2.6 kb, respectively; P = 0.009). Among individuals aged < 50 years, no significant difference was observed in TL between the non-OSA and OSA groups. However, among individuals aged ≥ 50 years, individuals without OSA had significantly longer telomeres than did individuals with moderate to severe OSA. Our findings indicate that telomere shortening was significantly more pronounced in patients with increasing OSA severity than in individuals without OSA. Nocturnal hypoxia-induced inflammation in patients with OSA may contribute to telomere shortening.},
}

@article {pmid40825569,
year = {2025},
author = {Patel, HR and Alreja, K and Reis, ALM and Chang, JK and Chew, ZA and Jung, H and Hammond, JM and Deveson, IW and Ruiz-Herrera, A and Marin-Gual, L and Holleley, CE and Zhang, X and Lister, NC and Whiteley, S and Xiong, L and Dissanayake, DSB and Waters, PD and Georges, A},
title = {A near telomere-to-telomere phased genome assembly and annotation for the Australian central bearded dragon Pogona vitticeps.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
pmid = {40825569},
issn = {2047-217X},
support = {//Bioplatforms Australia/ ; DP220101429//Australian Research Council/ ; APP2021172//National Health and Medical Research Council/ ; PID2020-112557GB-I00//Spanish Ministry of Science and Innovation/ ; //AEI/ ; 2021SGR00122//Agència de Gestió d'Ajuts Universitaris i de Recerca/ ; //Catalan Institution for Research and Advanced Studies/ ; FPU18/03867//Spanish Ministry of Science, Innovation and University/ ; EST22/00661//Spanish Ministry of Science, Innovation and University/ ; },
abstract = {BACKGROUND: The central bearded dragon (Pogona vitticeps) is widely distributed in central eastern Australia and adapts readily to captivity. Among other attributes, it is distinctive because it undergoes sex reversal from ZZ genotypic males to phenotypic females at high incubation temperatures. Here, we report an annotated near telomere-to-telomere phased assembly of the genome of a female ZW central bearded dragon.

RESULTS: Genome assembly length is 1.75 Gbp with a scaffold N50 of 266.2 Mbp, N90 of 28.1 Mbp, 26 gaps, and 42.2% GC content. Most (99.6%) of the reference assembly is scaffolded into 6 macrochromosomes and 10 microchromosomes, including the Z and W microchromosomes, corresponding to the karyotype. The genome assembly exceeds standard recommended by the Earth Biogenome Project (6CQ40): 0.003% collapsed sequence, 0.03% false expansions, 99.8% k-mer completeness, 97.9% complete single-copy BUSCO genes, and an average of 93.5% of transcriptome data mappable back to the genome assembly. The mitochondrial genome (16,731 bp) and the model ribosomal DNA repeat unit (length 9.5 Kbp) were assembled. Male vertebrate sex genes Amh and Amhr2 were discovered as copies in the small non-recombining region of the Z chromosome, absent from the W chromosome. This, coupled with the prior discovery of differential Z and W transcriptional isoform composition arising from pseudo-autosomal sex gene Nr5a1, suggests that complex interactions between these genes, their autosomal copies, and their resultant transcription factors and intermediaries determine sex in the bearded dragon.

CONCLUSION: This high-quality assembly will serve as a resource to enable and accelerate research into the unusual reproductive attributes of this species and for comparative studies across the Agamidae and reptiles more generally.},
}

@article {pmid40825568,
year = {2025},
author = {Guang, X and Yang, J and Zhang, S and Guo, F and Li, L and Lian, X and Zeng, T and Cai, C and Liu, F and Li, Z and Hu, Y and Fang, D and He, W and Sahu, SK and Li, W and Lu, H and Li, Y and Liu, H and Xu, X and Gu, Y and Hu, F and Dong, Y and Wei, T},
title = {Telomere-to-telomere African wild rice (Oryza longistaminata) reference genome reveals segmental and structural variation.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf074},
pmid = {40825568},
issn = {2047-217X},
support = {32322063 to S.Z.//National Natural Science Foundation of China/ ; KQTD20221101093603011 to J.Y.//Shenzhen Science and Technology Program/ ; },
abstract = {Rice (Oryza sativa) is one of the most important staple food crops worldwide, and its wild relatives serve as an important gene pool in its breeding. Compared with cultivated rice species, African wild rice (Oryza longistaminata) has several advantageous traits, such as resistance to increased biomass production, clonal propagation via rhizomes, and biotic stresses. However, previous O. longistaminata genome assemblies have been hampered by gaps and incompleteness, restricting detailed investigations into their genomes. To streamline breeding endeavors and facilitate functional genomics studies, we generated a 331-Mb telomere-to-telomere (T2T) genome assembly for this species using a hybrid approach combining PacBio HiFi, Hi-C, and CycloneSEQ ultra-long reads, covering all telomeres and centromeres across the 12 chromosomes. This newly assembled genome has markedly improved over previous versions. Comparative analysis revealed a high degree of synteny with previously published genomes. A large number of structural variations were identified between O. longistaminata, O. glaberrima, and O. sativa. A total of 2,466 segmentally duplicated genes were enriched in cellular amino acid metabolic processes. We detected slight expansion of some subfamilies of resistance genes and transcription factors. This newly assembled T2T genome of O. longistaminata provides a valuable resource for the exploration and exploitation of beneficial alleles present in wild relative species of cultivated rice.},
}

@article {pmid40820358,
year = {2025},
author = {Gao, H and Ma, K and Cao, Z and Hu, X and Wang, Y and Lu, M and Zhao, X and Zhou, J and Liu, Y and Wang, M and Zhao, Z and Wang, Z and Li, J and Li, Y and Qin, Y and Bao, X and Jing, Y and Wang, F and Yu, Z},
title = {Absolute Length Distribution of Human Telomeres with Single-Molecule Techniques.},
journal = {ACS nano},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsnano.5c11090},
pmid = {40820358},
issn = {1936-086X},
abstract = {Human telomeres exhibit progressive shortening with each replication cycle. This phenomenon plays a critical role in the onset of senescence and the development of cancers. The measurement of absolute telomere length (TL) is not only serving as a marker of aging, but also holds substantial medical relevance. However, current TL measurement technologies face significant challenges, including limited precision, inability to resolve TL heterogeneity or distinguish telomeric signals from interstitial telomeric sequences (ITS), and data inconsistency. Single-molecule mechanical techniques have shown promise in manipulating DNA and providing precise contour length measurements of DNA, making them suitable for assessing TL quantitatively. In this study, we developed a method, named single-molecule terminal restriction fragment (smTRF) analysis, for measuring telomeres at single-molecule resolution. We applied smTRF to seven human cancer cell lines and successfully determined TL ranging from a few to tens of kilobases, highlighting the versatility and high-fidelity performance of the smTRF assay. The smTRF data were validated against results from standard TRF, qPCR, and Q-FISH analysis, demonstrating well agreement and confirming the assay's reliability in the measurement of average TL. To further test the robustness of smTRF, we measured TL distribution profiles for 48 individuals, establishing the smTRF assay as a reliable tool for the accurate and precise measurement of human TLs. The comprehensive telomere profiles obtained via the smTRF assay promise to provide in-depth insights into public health research, particularly in the study of aging, where TL serves as a critical biomarker.},
}

@article {pmid40816244,
year = {2025},
author = {Sharma, B and Jamwal, RS and Chander, G and Sharma, M and Shah, R and Shankarayan, R and Bhan, S and Bhat, A and Bhat, AA and Kumar, R},
title = {Genetic insight into idiopathic male infertility in North India: Role of telomere maintenance genes.},
journal = {European journal of obstetrics, gynecology, and reproductive biology},
volume = {313},
number = {},
pages = {114653},
doi = {10.1016/j.ejogrb.2025.114653},
pmid = {40816244},
issn = {1872-7654},
abstract = {BACKGROUND: Despite having a sizeable population and an increasing incidence of infertility, South Asia is still underrepresented in genetic studies of male reproductive health. In this area, little is known about idiopathic male infertility, which is frequently associated with subtle genetic variations. Both TERT (chromosome 5 [5p15.33]) and TERF2 (chromosome 16 [16q22.1]) genes are essential for spermatogenesis, as TERT is needed to maintain the telomere length, and TERF2 aids in chromosomal integrity and cell division. The purpose of this study is to fill a regional gap in molecular reproductive research by examining the relationship between telomere related genes TERT and TERF2, and idiopathic male infertility in the Jammu and Kashmir population of North India.

METHODS: In this study, 634 cytogenetically normal individuals were enrolled, out of which 220 were male infertile patients and 414 were fertile male controls. Individuals who had AZF microdeletions in their Y chromosome were excluded from the study. TaqMan assay was used to genotype two SNP's, TERT (rs10069690) and TERF2 (rs251796), and statistical analysis was carried out using various genetic models.

RESULTS: Under the dominant model, a significant association was observed between TERT SNP rs10069690 (T > C) (OR = 6.17;95 % CI:3.5-10.6; p < 0.05). A statistically significant connection was not seen between male infertility and TERF2 variant rs251796 (G > A) (p = 0.09) CONCLUSIONS: This is the first report from North India to link male infertility to TERT gene polymorphism, suggesting that telomere maintenance may play a part in impaired spermatogenesis. These results highlight the significance of region-specific molecular screening in a larger population with increased sample size and may aid in advancement of predictive diagnosis for male reproductive health, particularly in South Asian populations that are undeserved.},
}

@article {pmid40813775,
year = {2025},
author = {Lv, Z and Wang, J and Zhou, L and Zou, S and Ai, L},
title = {Near telomere-to-telomere genome assembly of Camellia pitardii.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1422},
pmid = {40813775},
issn = {2052-4463},
abstract = {Camellia pitardii Cohen-Stuart, is an endemic winter-spring flowering wild Camellia species in southwestern China, with important ecological and horticultural value. Here, we report the near telomere-to-telomere (T2T) genome of C. pitardii by combining PacBio HiFi, ONT ultra-long, Hi-C and Illumina sequencing platforms. The genome size was 2.63 Gb, with repetitive content of 78.91% and contig N50 of 146.18 Mb. 95.5% of genomic sequences were anchored onto 15 chromosomes, including eight gap-free chromosomes, with 25 telomeres and 15 centromeres. A total of 52,848 protein-coding genes were predicted, of which 98.27% were functionally annotated. The genomic quality was further confirmed by the quality value (QV) of 44.87 and the Benchmarking Universal Single-Copy Orthologs (BUSCO) value of 96.34%. Comparative genomic analysis showed that C. pitardii had a close genetic relationship with C. oleifera and C. chekiangoleosa. The availability of C. pitardii near T2T genome will provide a foundation for identifying key genes related to stress resistance, flowering time regulation, and flower color formation, and promotes the breeding, utilization and conservation of the germplasm resources.},
}

@article {pmid40812670,
year = {2025},
author = {Niazi, SK},
title = {Telomere-targeted medicine: Bridging molecular mechanisms and clinical applications in age-related diseases.},
journal = {Life sciences},
volume = {379},
number = {},
pages = {123904},
doi = {10.1016/j.lfs.2025.123904},
pmid = {40812670},
issn = {1879-0631},
abstract = {Telomeres, the nucleoprotein structures at the ends of chromosomes, have emerged as critical regulators of cellular aging and key contributors to the pathogenesis of age-related diseases. This comprehensive review examines the evolution of telomere biology from fundamental research to therapeutic applications, analyzing molecular mechanisms of telomere dysfunction across diverse disease categories, including autoimmune disorders, cardiovascular diseases, neurodegeneration, respiratory diseases, metabolic disorders, chronic kidney disease, cancer, and premature aging syndromes. We explore current therapeutic strategies ranging from telomerase modulation to senolytic approaches, highlighting emerging technologies in drug discovery, including CRISPR-based interventions, nanomedicine, mRNA-based therapies, partial cellular reprogramming, and artificial intelligence applications. The convergence of mechanistic understanding with innovative therapeutic approaches positions telomere biology as a promising frontier for addressing multiple age-related conditions simultaneously, potentially shifting medicine from reactive disease treatment toward proactive aging-focused prevention. However, significant challenges remain, including safety considerations, biomarker development, and establishing regulatory frameworks for aging-targeted therapeutics. The success of telomere-targeted interventions could herald a paradigm shift toward geroscience-based medicine, extending lifespan and health span by targeting fundamental biological aging processes.},
}

@article {pmid40809889,
year = {2025},
author = {Zhang, B and Huang, Y and Li, X},
title = {Diets with higher inflammatory and insulinemic potential are associated with shorter relative telomere length.},
journal = {Nutrition research and practice},
volume = {19},
number = {4},
pages = {621-634},
pmid = {40809889},
issn = {1976-1457},
abstract = {BACKGROUND/OBJECTIVES: Telomere length is influenced by inflammation, insulin resistance, and hyperinsulinemia, which can be modulated by dietary factors. Nevertheless, it is still uncertain if diets with greater insulinemic or inflammatory potential are linked to shorter telomere length.

SUBJECTS/METHODS: This cross-sectional study analyzed the data from the National Health and Nutrition Examination Survey in the US. A total of 6,981 individuals were included, with an average age of 46.87 ± 0.36 yrs, and a female-to-male ratio of 1.12:1. Diet was obtained using 24-h recall. Three empirical dietary indices were developed, including the Empirical Dietary Inflammatory Pattern (EDIP), which identifies foods predictive of inflammation markers such as C-reactive protein and leukocyte count; the Empirical Dietary Index for Insulin Resistance (EDIR), which assesses insulin resistance via homeostatic model assessment; and the Empirical Dietary Index for Hyperinsulinemia (EDIH), which relates to hyperinsulinemia indicators including insulin and C-peptide. Relative telomere length (RTL) was measured by quantitative polymerase chain reaction. Percentage change (%), odds ratio (OR), and their 95% confidence intervals (CIs) were evaluated using linear and ordinal logistic regression, respectively.

RESULTS: EDIR (per 1 - SD increase, percentage change = -0.99%, 95% CI, -1.83%, -0.15%, P trend = 0.022; OR, 1.08, 95% CI, 1.01, 1.16, P trend = 0.018) and EDIH (percentage change = -1.03%, 95% CI, -1.94%, -0.11%, P trend = 0.030; OR, 1.07, 95% CI, 1.00, 1.15, P trend = 0.047) were associated with shorter RTL. EDIP showed a negative association with telomeres in ordinal logistic regression (OR, 1.07, 95% CI, 1.00, 1.15, P trend = 0.038), and this inverse association was more pronounced among participants with a light or vigorous activity in both regression (P interaction = 0.003; P interaction < 0.001).

CONCLUSION: Diets high in inflammation or insulinemic potential are associated with shorter RTL. The impact of EDIP is greater in individuals engaged in light or vigorous activity.},
}

@article {pmid40804293,
year = {2025},
author = {Zhang, M and Zhai, R and Niu, G and Chen, J and Tan, B and Wu, D and Meng, G and Wei, M},
title = {Telomere-to-telomere genome assembly uncovers Wolbachia-driven recurrent male bottleneck effect and selection in a sawfly.},
journal = {Communications biology},
volume = {8},
number = {1},
pages = {1211},
pmid = {40804293},
issn = {2399-3642},
support = {20232BAB215017//Natural Science Foundation of Jiangxi Province (Jiangxi Province Natural Science Foundation)/ ; },
abstract = {Wolbachia, a widespread endosymbiotic bacterium, profoundly impacts insect hosts by distorting reproduction and population dynamics. Despite extensive laboratory research, its long-term effects on host evolution in nature remain poorly understood, especially the genomic consequences linked to disruptions in sex determination and reproductive processes. We present the first telomere-to-telomere (T2T) genome assembly of the sawfly Analcellicampa danfengensis and the complete genome of its symbiotic Wolbachia. Comparative population genomics across six Analcellicampa species revealed that Wolbachia-infected populations show starkly different demographic signals. While uninfected populations show similar demographic signals for both sexes, infected populations exhibit a lower apparent effective population size (Ne) in males, which may reflect a recurrent male bottleneck effect driven by Wolbachia-induced male scarcity. Genomic scans identified positively selected genes associated with reproductive functions, sensory perception, neural development, and longevity, suggesting that Wolbachia likely manipulates critical host pathways to promote its transmission. These findings provide direct genomic insights into Wolbachia as an evolutionary force, highlighting specific host genes and regions under selection resulting from these altered evolutionary dynamics. This work provides deeper insights into host-endosymbiont coevolution and has important implications for evolutionary theory and pest management strategies.},
}

@article {pmid40804058,
year = {2025},
author = {Lian, Y and Wu, Y and Li, C and Wei, H and Du, P and Li, J and Lei, C and Li, H and Wang, S and Zhang, H and Wang, J and Lu, W},
title = {A telomere-to-telomere genome of wild soybean with resistance to soybean cyst nematode X12.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1412},
pmid = {40804058},
issn = {2052-4463},
abstract = {The soybean cyst nematode (SCN) is one of the most destructive pests affecting soybean production worldwide. Wild soybean (Glycine soja) germplasm offers valuable genetic resources for developing SCN-resistant cultivars. Here, we present a telomere-to-telomere assembly of the wild soybean Glycine soja accession YSD56, which is resistant to the highly virulent SCN race X12. The assembled genome has a total length of 1,008.52 Mb, with a contig N50 of 51.97 Mb, and successfully resolves all 20 centromeres and 40 telomeres. The assembly is high quality, with 99.7% completeness based on conserved single-copy orthologs (BUSCO) and a base-level accuracy of QV 52.16. A total of 57,712 protein-coding genes were predicted, 98.79% of which were functionally annotated. This high-quality reference genome provides a valuable resource for investigating SCN resistance and accelerating soybean genetic improvement.},
}

@article {pmid40803151,
year = {2025},
author = {Uzman Ozbek, S and Akyol, K and Bora, E},
title = {''Does bipolar disorder accelerate cellular aging? A systematic review and meta-analysis of telomere length''.},
journal = {European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology},
volume = {99},
number = {},
pages = {21-30},
doi = {10.1016/j.euroneuro.2025.07.007},
pmid = {40803151},
issn = {1873-7862},
abstract = {BACKGROUND: Recent research has suggested that bipolar disorder (BD) might be associated with accelerated aging. Multiple studies have shown telomere shortening in BD but others did not support this notion. In BD, TL can be influenced by factors such as aging, smoking, metabolic syndrome, the nature of the disorder, and lithium use. To evaluate differences in TL between individuals with BD and healthy controls and to explore potential factors influencing telomere shortening, we conducted a meta-analysis of studies comparing these populations.

METHODS: A systematic literature search was conducted in PubMed and Scopus databases up to November 2024. Original research articles reporting TL measures were selected.

RESULTS: A total of 24 studies, including 2330 patients diagnosed with BD and 2912 healthy controls, were included in the analysis. TL was significantly shorter in patients with BD compared to controls (Hedges' g, -0.42; 95% CI, -0.6 to -0.21; p <0.001). Meta-regression analyses showed that between-group differences in body mass index (BMI) had a significant effect on effect size. No statistically significant differences were found in subgroup analyses according to lithium use, duration of illness, telomere measurement method, substance use exclusion criteria, study quality, and euthymia. A moderate negative correlation was observed between age and TL in both BD and control groups (r=-0.38, r=-0.37).

CONCLUSION: Our results support the presence of illness-associated cellular aging in BD. Longitudinal studies with repeated TL measurements are needed to examine the potential effects of disease course, aging, illness duration, and medication on this process.},
}

@article {pmid40799616,
year = {2025},
author = {Williams, RS and Johnson, A and Miller-Perusse, M and Flentje, A and Moskowitz, J and Dilworth, SE and Horvath, KJ and Carrico, AW and Aouizerat, BE and Ghanooni, D},
title = {Outness predicts greater leukocyte telomere length in sexually minoritized men with HIV who use methamphetamine.},
journal = {Brain, behavior, & immunity - health},
volume = {48},
number = {},
pages = {101086},
pmid = {40799616},
issn = {2666-3546},
abstract = {OBJECTIVE: This longitudinal study aimed to examine the associations of sexual minority stress and outness with leukocyte telomere length across time among sexually minority men (SMM) with HIV who use methamphetamine.

METHODS: A sample of 91 SMM with HIV with biologically confirmed recent methamphetamine use completed measures of sexual minority stress and outness at the baseline visit in a randomized controlled trial. Telomere length was measured over 15 months using extracted leukocyte DNA Statistical analyses were performed using bivariate analyses and generalized estimation equations to examine the independent association between baseline outness and leukocyte telomere length, adjusting for chronological age and recent stimulant use.

RESULTS: Greater outness was significantly associated with longer telomere length (estimate = 0.008; CI: 0.001-0.008) after adjusting for chronological age and stimulant use. There was no evidence that stimulant use, intervention assignment, or race/ethnicity moderated the association between outness and greater leukocyte-telomere length. Sexual minority stress was not significantly associated with leukocyte-telomere length.

CONCLUSION: Findings are among the first to demonstrate that greater outness is associated with slower biological aging in SMM. Further research is needed to elucidate the bio-behavioral mechanisms linking outness and greater leukocyte-telomere length.},
}

@article {pmid40799400,
year = {2025},
author = {Bulut, O and Koeken, VACM and Moorlag, SJCFM and de Bree, CJ and Mourits, VP and Kilic, G and Debisarun, PA and Baltissen, MPA and Martens, JHA and Domínguez-Andrés, J and Joosten, LAB and Netea, MG},
title = {Long-term effects of BCG vaccination on telomere length and telomerase activity.},
journal = {iScience},
volume = {28},
number = {8},
pages = {113159},
pmid = {40799400},
issn = {2589-0042},
abstract = {This study explores the effects of Bacillus Calmette-Guérin (BCG) vaccination on telomere maintenance, an aging-related process, in immune cells. While BCG reduces systemic inflammation and enhances innate immune responsiveness by inducing trained immunity, its effects on other immune aging hallmarks, such as telomere shortening, are not fully understood. We assessed telomere length in two independent human cohorts before and three months after BCG vaccination. Telomere shortening was consistently observed after BCG, but not after placebo vaccination. Trained immunity non-responders were likelier to lose telomere length, but only among males. Higher pre-vaccination testosterone levels were associated with greater telomere loss in males. In vitro, BCG training activated telomerase, particularly in females, and this was partially prevented by exogenous testosterone. These findings suggest BCG vaccination influences telomere dynamics in a sex-specific manner, contributing to understanding BCG's broader effects on aging-related processes.},
}

@article {pmid40796147,
year = {2025},
author = {Hospodářská, M and Koutecký, P and Koutková, S and Vila, R and Talavera, G and Rindoš, M and Provazníková, I and Dalíková, M and Nguyen, P},
title = {Polyommatine blue butterflies reveal unexpected integrity of the W sex chromosome amid extensive chromosomal fragmentation linked to telomere restoration.},
journal = {Genome biology and evolution},
volume = {},
number = {},
pages = {},
doi = {10.1093/gbe/evaf157},
pmid = {40796147},
issn = {1759-6653},
abstract = {Chromosomal rearrangements act as barriers to gene flow and can thus promote speciation. In moths and butterflies (Lepidoptera), which possess holocentric chromosomes facilitating karyotype changes, chromosome fusions are more common than fissions. Yet, limited evidence suggests that when speciation involves chromosomal rearrangements, it is most often linked to fissions. Notable karyotypic variation is observed in three clades of the subfamily Polyommatinae (Lycaenidae), with chromosome numbers ranging from n = 10 to n = 225. We investigated genome sizes and karyotypes in several species of the genera Polyommatus and Lysandra with modal and derived high chromosome numbers. Our findings showed no support for polyploidy, confirming previous conclusions about karyotypic diversification via chromosome fragmentation in this butterfly family. Species with high chromosome numbers have slightly larger genomes, which indicate a potential role of repetitive sequences but contradicts the hypothesis of holocentric drive. Ends of fragmented chromosomes were healed with telomeres synthesized de novo, which were significantly larger than those of species with modal karyotype. No interstitial telomeric sequences were detected on autosomes. Internal telomeric signals on sex chromosomes, however, revealed multiple sex chromosome systems in Polyommatus (Plebicula) dorylas and Polyommatus icarus, with two karyotype races differing in sex chromosome constitution in the latter. Notably, the W chromosome resisted fragmentation, presumably due to its epigenetic silencing.},
}

@article {pmid40795958,
year = {2025},
author = {Lee, J and Sohn, EJ and Lee, J and Cheng, AY and Taglialatela, A and Ciccia, A and Min, J},
title = {Distinct mechanisms underlying extrachromosomal telomere DNA generation in ALT cancers.},
journal = {Nucleic acids research},
volume = {53},
number = {15},
pages = {},
doi = {10.1093/nar/gkaf771},
pmid = {40795958},
issn = {1362-4962},
support = {R35GM155138/GF/NIH HHS/United States ; R01CA197774/GF/NIH HHS/United States ; //National Research Foundation of Korea/ ; RS-2024-00410165//Ministry of Education/ ; //Amgen Scholars/ ; },
abstract = {Alternative lengthening of telomeres (ALT) is a telomerase-independent telomere maintenance mechanism observed in 15% of human cancers. A hallmark of ALT cancers is the presence of C-circles, circular single-stranded DNAs (ssDNAs) enriched with cytosine-rich telomere (C-rich, CCCTAA) sequences. G-circles, containing guanosine-rich telomere (G-rich, GGGTTA) ssDNAs, also exist but are much less abundant. Recent studies indicate that excessive displacement of Okazaki fragments during lagging-strand synthesis is a unique feature of ALT telomeres and responsible for generating C-circles/C-rich ssDNAs. However, the distinct characteristics of C-circles compared to G-circles remain unclear. Here, we demonstrate that co-deficiency of the DNA translocases SMARCAL1 and FANCM leads to abundant generation of G-circle/G-rich ssDNAs. These G-rich ssDNAs mainly exist in linear form, ranging in size from 500 to 3000 nucleotides, which differs significantly from the structure and size of C-circle/C-rich ssDNAs. Mechanistically, both C-rich and G-rich ssDNAs originate from BLM/POLD-mediated excessive strand displacement; however, they differ in their origins and initiation mechanisms. Specifically, C-rich ssDNAs arise from lagging daughter strands initiated by the CST complex, whereas G-rich ssDNAs originate from leading daughter strands through RAD51-dependent G-strand synthesis. Our findings propose two distinct mechanisms for generating two different extrachromosomal telomere DNAs, C- and G-circles, during ALT-mediated telomere elongation.},
}

@article {pmid40791717,
year = {2025},
author = {Andrews, SJ and Mitchell, BA and Tong, T and Bonham, LW and Renton, AE and Zhang, X and Sirota, M and Tosun, D and Yaffe, K and , },
title = {Integrative effects of Telomere Length, Epigenetic Age, and Mitochondrial DNA abundance in Alzheimer's Disease.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.07.16.25331683},
pmid = {40791717},
abstract = {BACKGROUND AND OBJECTIVES: Biological age, reflecting the cumulative molecular and cellular damage such as telomere attrition, epigenetic alterations and mitochondrial dysfunction, may better capture age-related decline and Alzheimer's disease (AD) risk than chronological age. Most studies have focused on one measure of biological age and not investigated joint or interactive contributions to AD pathogenesis.

METHODS: We estimated blood-derived telomere length (TL) via qPCR, epigenetic age (DNAm age) using the CausAge clock, and mitochondrial DNA copy number (mtDNAcn) from whole genome sequencing in 640 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI; Age: 74.91±7.56, Female: 44.8%, Cognitively Unimpaired: 34.3%, Mild Cognitive Impairment: 52%, AD: 12.9%). Linear mixed-effects models examined the associations and interactions of these markers with cognitive decline for memory, executive function, language ability, visuospatial ability, and global cognition, while linear regression tested associations with cross-sectional AD biomarkers (CSF Aβ 42 , total-tau, pTau 181 , and meta-ROI for cortical thickness and gray matter volume). Models adjusted for baseline age, sex, clinical dementia rating scale, APOE , blood cell composition, and outcome-specific covariates (education and intracranial volume).

RESULTS: Individually, TL and DNAm age, were not associated with cognition, CSF biomarkers, or neuroimaging outcomes, while higher mtDNAcn was associated with lower CSF tau and ptau 181 . Interaction models revealed that mtDNAcn modified the effects of both TL and DNAm age: at higher mtDNAcn, shorter TL predicted poorer global cognition (β = 0.033 ± 0.014, p = 0.020) and older DNAm age predicted poorer language performance (β = -0.059 ± 0.028, p = 0.038). A significant three-way interaction showed that the combination of higher mtDNAcn, longer TL, and older DNAm age was associated with lower grey-matter volume.

DISCUSSION: These findings suggest that increased mtDNAcn may act as a compensatory response to accelerated epigenetic aging and telomere attrition. Our results underscore the importance of evaluating the interplay among multiple biological aging markers when investigating AD pathogenesis.},
}

@article {pmid40791463,
year = {2025},
author = {Nguyen, L and Choi, JY},
title = {Topsicle: a method for estimating telomere length from whole genome long-read sequencing data.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.07.10.664126},
pmid = {40791463},
issn = {2692-8205},
support = {R35 GM154595/GM/NIGMS NIH HHS/United States ; },
abstract = {Telomeres protect chromosome ends and its length varies significantly between organisms. Because telomere length variation is associated with various biomedical and eco-evolutionary phenotypes, many biological fields are interest in understanding its biological significance. Here we introduce Topsicle, a computational method that estimates telomere length from whole genome long read sequencing data using k-mer and change point detection analysis. Simulations showed Topsicle was robust to sequencing errors and coverage. Application of Topsicle on plant and human cancer cells showed high accuracy and comparable results to direct telomere length measurements. We predict Topsicle will be a useful tool for studying telomere biology. Topsicle is available at https://github.com/jaeyoungchoilab/Topsicle.},
}

@article {pmid40789644,
year = {2025},
author = {Nassour, J and Karlseder, J},
title = {Telomere Crisis Shapes Cancer Evolution.},
journal = {Cold Spring Harbor perspectives in biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/cshperspect.a041688},
pmid = {40789644},
issn = {1943-0264},
abstract = {Somatic mutations arise in normal tissues and precursor lesions, often targeting cancer-driver genes involved in cell cycle regulation. Most checkpoint-mutant clones, however, remain dormant throughout an individual's lifetime and seldom progress to malignancy, implying the presence of protective mechanisms that limit their expansion and malignant transformation. One such safeguard is telomere crisis-a potent tumor-suppressive barrier that eliminates cells lacking functional checkpoints and evading p53- and pRb-mediated surveillance. While the genomic instability unleashed during telomere crisis can drive clonal evolution, cell death is typically the dominant outcome, with only a rare subset of cells escaping elimination to initiate malignancy. Recognizing the dual role of telomere crisis-suppressing tumor initiation while enabling clonal evolution-is essential for understanding early cancer development and designing strategies to eliminate tumor-initiating cells.},
}

@article {pmid40787955,
year = {2025},
author = {Li, DY and Yu, S and Yang, BH and Zhang, JB and Yin, GC and Wu, LN and Dong, QZ and Xu, JL and Ning, SP and Zhao, R},
title = {[Exploring the causal relationship between leukocyte telomere length and prostatitis, orchitis, and epididymitis based on a two-sample Mendelian randomization].},
journal = {Zhonghua nan ke xue = National journal of andrology},
volume = {31},
number = {4},
pages = {306-312},
pmid = {40787955},
issn = {1009-3591},
mesh = {Humans ; Male ; Mendelian Randomization Analysis ; *Epididymitis/genetics ; *Prostatitis/genetics ; Polymorphism, Single Nucleotide ; *Leukocytes ; *Orchitis/genetics ; Genome-Wide Association Study ; *Telomere ; Risk Factors ; },
abstract = {OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR).

METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method.

RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6).

CONCLUSION: Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.},
}

Humans
Male
Mendelian Randomization Analysis
*Epididymitis/genetics
*Prostatitis/genetics
Polymorphism, Single Nucleotide
*Leukocytes
*Orchitis/genetics
Genome-Wide Association Study
*Telomere
Risk Factors

@article {pmid40783646,
year = {2025},
author = {Hernandez-Castro, I and Rifas-Shiman, SL and Panelli, DM and Smith, AR and Yi, L and Aris, IM and Tiemeier, H and Belfort, MB and Qureshi, F and Gold, DR and Hivert, MF and Oken, E and Cardenas, A},
title = {Associations of maternal neighborhood and trauma-related stressors with mitochondrial DNA copy number and telomere length in maternal and cord blood.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {29143},
pmid = {40783646},
issn = {2045-2322},
support = {Stanford//Propel Fellowship/ ; R01ES031259, UG3 OD023286, P30-ES000002, U2CES026561, R01HD034568, R24ES030894//U.S. National Institutes of Health/ ; },
mesh = {Humans ; Female ; *DNA, Mitochondrial/genetics ; *Fetal Blood/metabolism ; Pregnancy ; Adult ; *DNA Copy Number Variations ; *Telomere/genetics ; *Residence Characteristics ; *Telomere Homeostasis ; *Stress, Psychological/genetics ; Oxidative Stress ; Adverse Childhood Experiences ; },
abstract = {Neighborhood and individual-level trauma-related stressors during pregnancy can increase oxidative stress, potentially altering cellular disease pathway biomarkers such as mitochondrial DNA copy number (mtDNAcn) and telomere length (TL). However, the biological mechanisms linking early-life stressors to long-term health outcomes remain understudied. In a subset of Project Viva participants (n = 415-917), we evaluated associations of neighborhood and individual-level stressors with mean relative mtDNAcn and TL measured in first trimester maternal blood and cord blood. Neighborhood stressors during pregnancy were assessed using the Child Opportunity Index (COI) and Social Vulnerability Index (SVI). Trauma-related stressors were measured using the Personal Safety Questionnaire (PSQ), administered mid-pregnancy, and maternal Adverse Childhood Experiences (ACEs), reported during a mid-life follow-up. In multivariable linear regression analysis, residence in a very high versus very low opportunity neighborhood was associated with lower maternal mtDNAcn ([Formula: see text]= - 0.09, 95% confidence interval (CI) - 0.17, - 0.02), while residence in a very high versus very low vulnerability area was associated with higher maternal mtDNAcn ([Formula: see text]= 0.06, 95% CI 0.01, 0.12). Additionally, residence in moderate versus very low opportunity neighborhoods was associated with longer cord blood TL ([Formula: see text]= 0.39, 95% CI 0.0002, 0.78), but associations were attenuated after cell-type adjustment. Our findings suggest that prenatal neighborhood stressors are associated with increased maternal mtDNAcn and neighborhood opportunity is associated with longer fetal TL, indicating possible links to biological pathways related to oxidative stress and cellular aging.},
}

Humans
Female
*DNA, Mitochondrial/genetics
*Fetal Blood/metabolism
Pregnancy
Adult
*DNA Copy Number Variations
*Telomere/genetics
*Residence Characteristics
*Telomere Homeostasis
*Stress, Psychological/genetics
Oxidative Stress
Adverse Childhood Experiences

@article {pmid40783018,
year = {2025},
author = {Yang, F and Peng, S and Yuan, S and Ran, M and Li, X and Li, Y and Liu, B and Li, M and Kong, C and Yang, X and Pan, G and Yong, X and Ran, K and Kuang, N and Zhang, D and Lin, H},
title = {A telomere-to-telomere genome assembly of radish (Raphanus sativus L.) provides insights into QTL mapping of bolting traits.},
journal = {Journal of genetics and genomics = Yi chuan xue bao},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jgg.2025.07.014},
pmid = {40783018},
issn = {1673-8527},
abstract = {Radish (Raphanus sativus L.) is an important cruciferous root vegetable, with bolting regulated by multiple genes; however, the genetic mechanisms underlying bolting regulation remain unclear. Here, the genome of the cultivar C60213 is assembled into a high-quality, gap-free telomere-to-telomere structure, spanning nine chromosomes and totaling 472.71 Mb, using a combination of Oxford Nanopore, PacBio, and Hi-C sequencing technologies. It identifies 49,768 protein-coding genes, 97.38% of which are functionally annotated. Repetitive sequences constitute 59.72% of the genome, primarily comprising long terminal repeats. A high-density genetic linkage map is constructed using an F2 population derived from a cross between early- and late-bolting radishes, identifying seven major quantitative trait loci associated with bolting and flowering. RNA-seq and quantitative real-time PCR analysis reveal that the RsMIPS3 gene is found to be associated with bolting, with its expression decreasing during this process. Notably, RsMIPS3 overexpression in Arabidopsis delays bolting, confirming its role in regulating bolting time. These findings advance radish genome research and provide a valuable target for breeding late-bolting varieties.},
}

@article {pmid40781257,
year = {2025},
author = {Carlund, O and Norberg, A and Osterman, P and Andersson, I and Eriksson, A and Degerman, S and Hultdin, M},
title = {Telomerase activity in T-cells as a functional test for pathogenicity assessment of novel genetic variants in telomere biology disorders.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {29048},
pmid = {40781257},
issn = {2045-2322},
mesh = {Humans ; *Telomerase/genetics/metabolism ; *Telomere/genetics/metabolism ; *T-Lymphocytes/enzymology/metabolism ; Male ; Female ; *Genetic Variation ; Dyskeratosis Congenita/genetics ; Adult ; RNA/genetics ; },
abstract = {The telomerase enzyme is essential for telomere maintenance. Pathogenic variants in telomere-associated genes have been associated with critical telomere shortening, resulting in telomere biology disorders (TBD) such as bone marrow failure, idiopathic pulmonary fibrosis, and dyskeratosis congenita. The TBDs are clinically heterogeneous and families with TBD often experience an earlier onset and increased symptom severity for each generation. Consensus guidelines have identified certain genetic variants as pathogenic or likely pathogenic, but many are classified as variants of uncertain significance (VUS) in the absence of additional supporting evidence. The pathogenicity of a VUS in genes encoding the telomerase complex could be evaluated by in vitro telomerase activity (TA) measurement. We have developed a functional TA assay in patient-derived T-cells based on the Telomeric Repeat Amplification Protocol (TRAP) combined with qPCR. TA was significantly lower in six TBD patients with a TERT or TERC variant compared to controls (0.11 versus 0.54, p < 0.001). Four patients had a TA of more than three standard deviations below the mean of controls, strongly supporting pathogenicity of the variants. In summary, functional analysis of TA in patient-derived cells could support pathogenic evaluation in clinical diagnostics and reduce the number of reported VUS for TBD patients.},
}

Humans
*Telomerase/genetics/metabolism
*Telomere/genetics/metabolism
*T-Lymphocytes/enzymology/metabolism
Male
Female
*Genetic Variation
Dyskeratosis Congenita/genetics
Adult
RNA/genetics

@article {pmid40781181,
year = {2025},
author = {Cushing, LJ and Caballero-Gomez, H and Eick, SM and Guimaraes, ACP and Depsky, NJ and DeMicco, E and Lin, J and Woodruff, TJ and Morello-Frosch, R},
title = {Neighborhood built environment, psychosocial stressors, and telomere length of birth parents and their newborns from San Francisco, California.},
journal = {Journal of exposure science & environmental epidemiology},
volume = {},
number = {},
pages = {},
pmid = {40781181},
issn = {1559-064X},
abstract = {BACKGROUND: Shorter telomere length is a biomarker of cellular aging influenced in early life. Exposure to environmental hazards and psychosocial stressors disproportionately impact socially marginalized populations and have been linked with shorter telomeres.

OBJECTIVE: To estimate joint associations between residential neighborhood greenness, traffic, noise, and perceived neighborhood quality, psychosocial stress and depression on telomere length of birth parents and their newborns.

METHODS: Telomere length (T/S ratio) was measured in leukocytes from 354 2nd trimester parental and 488 umbilical cord blood samples collected at delivery from the Chemicals in Our Bodies cohort in San Francisco, California. Normalized difference vegetation index (NDVI), traffic volume, and noise were estimated based on residential address. Perceptions of neighborhood quality, psychosocial stress, and depression were collected via questionnaire. We used quantile g-computation to assess joint associations between all exposures and newborn and parental T/S in separate models controlling for parental age, race and ethnicity, education, pre-pregnancy body mass index, and gestational age (cord T/S only). We used interaction terms to assess effect measure modification by nativity, race and ethnicity, and educational attainment.

RESULTS: Parental and newborn T/S were not correlated with individual measures of built environment or psychosocial stressors (rho from -0.08 to 0.08). A simultaneous one quartile increase in all adverse exposures was associated with a decrease in newborn T/S (mean difference [95% CI] = -0.03 [-0.08, 0.01]) that was stronger when restricting to paired parental-newborn samples and controlling for parental T/S (-0.08 [-0.15, -0.01]). Interaction analysis revealed stronger associations among immigrant (-0.08 [-0.16, 0.00]) vs. US-born (-0.02 [-0.07, 0.04]) and college-educated (-0.07 [-0.12, -0.02]) vs. non-college educated (0.03 [-0.07, 0.12]) participants. We saw no association with parental telomere length.

SIGNIFICANCE: Results suggest exposure to adverse neighborhood built environments and individual-level psychosocial stressors during pregnancy is associated with reductions in telomere length among newborns.

IMPACT: Telomere length at birth predicts relative telomere length in adulthood, suggesting much of the link between telomere length and longevity is established early in life. While neighborhood environments have been linked with shorter telomeres in adulthood, few prior studies have assessed newborn telomere length or joint associations with psychosocial stressors. In a diverse birth cohort, we show that the mixture of neighborhood lack of greenness, traffic, and noise, coupled with individual-level poor perceptions of neighborhood quality, stress, and depression is associated with decreased telomere length among newborns, with slightly stronger effects among immigrants and college-educated birth parents.},
}

@article {pmid40775495,
year = {2025},
author = {Han, C and Zhang, Y and Liang, H and Chen, M and Li, J and Hua, Z},
title = {The telomere-to-telomere chromosome-scale genome assembly of Acremonium chrysogenum.},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1378},
pmid = {40775495},
issn = {2052-4463},
mesh = {*Acremonium/genetics ; *Telomere ; *Genome, Fungal ; Cephalosporins/biosynthesis ; *Chromosomes, Fungal ; Genome, Mitochondrial ; },
abstract = {Acremonium chrysogenum is a notable filamentous fungus recognized for its essential contribution to the pharmaceutical sector through the biosynthesis of cephalosporin C (CPC). CPC functions as a key intermediate in the biosynthesis of β-lactam antibiotics, which are employed to combat bacterial infections. This study successfully generated a telomere-to-telomere (T2T) chromosome-scale genome sequence for A. chrysogenum, combining BGI short reads, PacBio HiFi long reads, and Hi-C technology. This genome sequence contained eight complete chromosomes (29.00 Mb) and a circular mitochondrial genome (27.27 kb), featuring an N50 length of 3.87 Mb. Repetitive elements accounted for 9.65% of genomic content, and a total of 7,745 genes involved in protein coding were annotated. This well-assembled reference genome of A. chrysogenum serves as an important foundation for elucidating the biosynthetic pathway of cephalosporin C and for molecular breeding. Furthermore, it offers valuable insights into chromosome organization, genome evolution, and regulatory mechanisms, facilitating future advancements in antibiotic research and fungal biotechnology.},
}

*Acremonium/genetics
*Telomere
*Genome, Fungal
Cephalosporins/biosynthesis
*Chromosomes, Fungal
Genome, Mitochondrial

@article {pmid40774081,
year = {2025},
author = {Goumy, C and Sudy, T and Coudrieu, O and Ouedraogo, ZG and Murer, N and Darcha, C and Darcha, C and Veronese, L and Tchirkov, A},
title = {Shorter umbilical cord telomere length is associated with fetal developmental anomalies and pregnancy loss.},
journal = {Placenta},
volume = {170},
number = {},
pages = {1-7},
doi = {10.1016/j.placenta.2025.07.089},
pmid = {40774081},
issn = {1532-3102},
abstract = {INTRODUCTION: Maintaining telomere length (TL) is crucial for cell division during embryogenesis and morphogenesis. Our initial study, conducted on amniotic fluid and chorionic villi samples, have suggested a link between shortened telomeres and abnormal fetal development. This new study aims to confirm these findings in umbilical cord (UC) samples.

METHODS: TL was analyzed by qPCR in 204 UC samples collected from cases of pregnancy loss, including 130 cases without developmental abnormalities, 62 with congenital malformations, and 12 with intrauterine growth restriction (IUGR). UC samples (n = 21) obtained from planned caesarean sections without fetal or neonatal distress were used as controls.

RESULTS: We observed a significant reduction of TL in case of malformations and IUGR (P < 0.0001). We observed that the reduction of TL was associated with the severity of malformations. We also analyzed TL according to the type of pregnancy loss. A significantly lower TL was observed in cases of spontaneous abortion (P = 0.002).

DISCUSSION: Our results show associations between the presence of UC short telomeres and the occurrence of congenital malformation, IUGR, and spontaneous abortion. An UC biopsy is a minimally invasive sample that can be easily obtained at birth and is suitable for studying fetal telomere biology in cases of developmental anomalies. Our hypothesis is that a defect in the mechanisms of TL maintenance would lead to the presence of short telomeres, limiting the proliferative capacity of embryonic cells and altering organogenesis and development. In clinical practice, geneticists should pay particular attention to genes involved in TL regulation when interpreting genome sequencing data, especially in cases of developmental abnormalities or recurrent miscarriages.},
}

@article {pmid40772020,
year = {2025},
author = {Luealai, P and Pongcharoen, T and On-Nom, N and Suttisansanee, U and Temviriyanukul, P and Kriengsinyos, W and Khemthong, C and Chupeerach, C},
title = {Shortening Leukocyte Telomere Length Associated With Elevated Blood Diabetes-Related Cardiovascular Risk Factor in Thai Adolescents.},
journal = {Food science & nutrition},
volume = {13},
number = {8},
pages = {e70546},
pmid = {40772020},
issn = {2048-7177},
abstract = {Leukocyte telomere length (LTL) is considered a reliable biological indicator of aging. LTL shortening has been associated with an increased risk of cardiometabolic markers among adults. However, evidence for an association in adolescents is limited. This cross-sectional study examined the association between blood biomarkers of cardiovascular diseases and leukocyte telomere length in 59 Thai adolescents with mean age 15 years. Blood samples and anthropometric, clinical, and biochemical data were collected, with relative telomere length (RTL) measured using the quantitative polymerase chain reaction (qPCR) method. Results showed that RTL was negatively associated with Hemoglobin A1C (HbA1C) but positively associated with high density lipoprotein cholesterol (HDL-C). Inflammatory Tumor necrosis factor alpha (TNF-α) was positively correlated with RTL, with a strong association in female adolescents. After adjusting the confounding factors including age, gender, and body mass index (BMI) for age the multivariable models indicated that predictors of shortening RTL were higher levels of HbA1C (β = -0.444, p = 0.002) and lower in HDL-C (β = 0.025, p = 0.002). The results suggested a positive association between telomere length and cardiometabolic risk factors such as HbA1C and HDL-C in Thai adolescent subjects. To confirm these findings, a longitudinal study should be conducted in the future with a larger sample size with considering of environment factors.},
}

@article {pmid40768485,
year = {2025},
author = {Xu, P and Wu, F and Yan, Q and Ao, B and Wang, S and Chen, L and Wang, L and Zhang, J},
title = {Hybridization Drives Trait Integration in Telomere-To-Telomere Apocynum Genomes.},
journal = {Plant biotechnology journal},
volume = {},
number = {},
pages = {},
doi = {10.1111/pbi.70288},
pmid = {40768485},
issn = {1467-7652},
support = {23ZDKA013//Gansu Province Chief Scientist Responsibility Program (23ZDKA013)/ ; },
abstract = {Hybridization drives plant adaptation, yet its genomic mechanisms in non-model perennials remain elusive. Apocynum species thrive in extreme saline-alkaline environments. This study establishes A. pictum (APZ) as a homoploid hybrid of A. venetum (AVX) and A. hendersonii (AHG), exemplifying hybrid-driven resilience. Leveraging telomere-to-telomere (T2T) genome assemblies of AVX, APZ, and AHG, we confirmed APZ's hybrid origin ~0.95 million years ago (Mya), following species divergence ~2.08 Mya, with AHG plastid inheritance. Nuclear and plastid analyses resolve taxonomic disputes among three Apocynum species. APZ exhibits large heterozygous inversions on chromosomes 3 and 8 with suppressed recombination, preserving AHG stress-tolerance haplotypes. The study also showed that allele-specific expression (ASE) dynamically regulates salt tolerance: AHG-biased stress MAPK signalling pathway prevails at 200 mM NaCl, shifting to AVX-bias at 400 mM NaCl, while flavonoid biosynthesis genes such as AvFLS and AvCHS5 consistently favour AVX alleles. Transgenic assays validate AVX-derived AvFLS for superior salt tolerance and ROS scavenging, with AvCHS5 diversification driven by tandem duplication dosage effects. Homoploid hybrid speciation (HHS) analysis indicates AvCHS5 and circadian LHY genes under positive selection enhance hybrid stability, supporting breeding potential. This study reveals how hybridization drives trait integration via dynamic ASE, identifying AvFLS, AvCHS5, and stress-responsive loci as breeding targets for stress-resilient, flavonoid-rich cultivars, offering a genomic foundation for crop improvement in extreme environments.},
}

@article {pmid40767284,
year = {2025},
author = {Parikh, RR and Pankratz, N and Lane, JA and Arking, DE and Eaton, A and Chen, LY and Lutsey, PL and Tang, W},
title = {Associations of Midlife Leukocyte Telomere Length With Measures of Left Atrial Function in Community-Dwelling Older Adults: The ARIC Study.},
journal = {Journal of the American Heart Association},
volume = {},
number = {},
pages = {e040459},
doi = {10.1161/JAHA.124.040459},
pmid = {40767284},
issn = {2047-9980},
abstract = {BACKGROUND: It is unknown whether atrial myopathy, ascertained by poor left atrial (LA) function, is associated with biological aging independent of chronological age. Such an association would indicate that atrial myopathy may be preventable by intervening on modifiable risk factors that accelerate aging. Therefore, we evaluated associations of midlife leukocyte telomere length (LTL, a measure of biological aging) with measures of LA function (a surrogate for LA myopathy).

METHODS: We included 4376 adults (mean age, 75 years; 41.11% men; 16.36% Black individuals) from the ARIC (Atherosclerosis Risk in Communities) study. We measured LA function as LA reservoir, conduit, and contractile strain using 2-dimensional speckle tracking echocardiography (2011-2013). We used TelSeq software to estimate LTL from whole genome sequencing data collected in midlife (1987-1998; mean age, 55 years). LTL estimates were inverse normalized within read length group and whole genome sequencing platform before being merged. We used linear regression to estimate the associations of LTL with LA function.

RESULTS: LTL was weakly correlated with chronological age at blood draw for LTL measurement (r=-0.12; P<0.001). In models adjusted for chronological age at blood draw for LTL measurement, whole genome sequencing platform, visit for blood draw, cardiometabolic risk factors, and coronary heart disease, longer LTL was associated with greater (better) LA contractile strain (β=0.29 [95% CI, 0.10-0.47]; P=0.006) and LA reservoir strain (β=0.35 [95% CI, 0.12-0.59]; P=0.003) but not LA conduit strain (β=0.05 [95% CI, -0.12 to 0.21]; P=0.575).

CONCLUSIONS: Greater biological aging may adversely impact LA substrate independent of chronological aging.},
}

@article {pmid40762785,
year = {2025},
author = {Nanda, A and Aslan, DH and Sayre, MK and Bharadwaj, PK and Ally, M and Song, H and Arora, A and Maltagliati, S and Lai, MHC and Wilcox, RR and Klimentidis, YC and Alexander, GE and Raichlen, DA},
title = {Chronic inflammation mediates the relationship between physical activity and telomere length.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {40762785},
issn = {2509-2723},
support = {P30AG072980//National Institute of Health/ ; P30AG019610//National Institute of Health/ ; R56AG067200//National Institute of Health/ ; R01AG064587//National Institute of Health/ ; R01AG72445//National Institute of Health/ ; },
abstract = {A physically active lifestyle benefits cellular aging, however the mechanisms linking physical activity (PA) with longevity remain unclear. PA is associated with longer telomere length (TL), while shorter TL has been associated with increased cellular aging. Some research suggests increased levels of inflammatory markers, such as C-reactive protein (CRP), are associated with telomere dysfunction. We tested the hypothesis that CRP levels mediate the association between PA and TL. Using data from the UK Biobank, we analyzed adjusted leukocyte T/S ratio (relative telomere to single gene copy), serum CRP, and moderate-to-vigorous physical activity (MVPA) data via device-measured actigraphy. We applied general linear regressions and a causal mediation analysis with 10,000 bootstraps while controlling for a range of covariates (age, BMI, smoking status, sex, ethnicity, time between data collection, time wearing the accelerometer, and the Townsend Deprivation Index). Variables of interest were transformed to approximate normality. A total of 79,873 participants were included in the final analytic sample. MVPA and CRP were both significant predictors of TL (βMVPA = 3.03e - 03 [95%CI = 1.58e - 03, 4.47e - 03], pMVPA = 4.10e - 05; βCRP = - 1.36e - 03 [95%CI = - 1.87e - 03, - 8.40e - 04], pCRP = 2.52e - 07, respectively). The association between MVPA and TL was mediated by CRP, accounting for 8.65% [95% CI: 4.77%, 16.0%] of the total effect (β [95%CI] = 3.31e - 03 [1.84e - 03, 4.75e - 03], p < 2e - 16). Our analysis supports the hypothesis that CRP mediates the relationship between MVPA and TL. These novel findings suggest a potential pathway where PA is associated with lower CRP concentrations, which in turn is associated with longer average TL.},
}

@article {pmid40762130,
year = {2025},
author = {Niknafs, AM and Giri, N and Niewisch, MR and Savage, SA},
title = {Avascular Necrosis and Minimal Trauma Fractures in Telomere Biology Disorders.},
journal = {Clinical genetics},
volume = {},
number = {},
pages = {},
doi = {10.1111/cge.70038},
pmid = {40762130},
issn = {1399-0004},
support = {Z01 CP010144/ImNIH/Intramural NIH HHS/United States ; },
abstract = {Avascular necrosis (AVN) and minimal trauma fractures (MTF) cause significant morbidity in patients with telomere biology disorders (TBDs). TBDs are associated with very high risks of bone marrow failure, pulmonary fibrosis, cancer, and many other complications due to pathogenic germline variants in genes essential for telomere function and maintenance. To understand the extent to which AVN and MTF occur in TBDs and identify areas requiring more research in the role of telomeres in bone biology. We assessed the occurrence of AVN and MTF in 233 patients with TBDs. An age, gender, and gene-matched TBD patient control group was used to assess associations between AVN/MTF and clinical characteristics. Forty-two (18%) patients with TBD developed at least one AVN and/or MTF event with 19 patients experiencing their first event in childhood. AVN and MTF were most common in patients with autosomal or X-linked recessive, or heterozygous TINF2 disease (19/36 AVN and 17/19 MTF). Androgen and corticosteroid use were more common in patients with AVN compared with matched patient controls (41.2% vs. 16.3%, p < 0.05 and 41.2% vs. 14%, p < 0.01, respectively); however, 57.1% of patients experienced AVN and/or MTF events in the absence of androgen or corticosteroid use. Severe bone marrow failure and hematopoietic cell transplantation history were significantly more common in MTF patients than in controls (44.2% and 30.2% respectively, p < 0.05). There were no statistically significant associations between low bone mineral density or vitamin D deficiency and AVN or MTF. AVN and MTFs are common, debilitating complications in TBDs and frequently occur independently of androgen or corticosteroid use. Our results underscore the need for disease-specific translational studies as well as improved prevention and therapeutic options for patients with TBDs. Trial Registration: ClinicalTrials.gov identifier: NCT00027274.},
}

@article {pmid40761438,
year = {2025},
author = {Livings, MS and Smith-Greenaway, E and Wagner, BG and Verdery, AM},
title = {The biological consequences of grandparental death for children: An analysis of telomere length.},
journal = {SSM - population health},
volume = {31},
number = {},
pages = {101843},
pmid = {40761438},
issn = {2352-8273},
abstract = {Increasingly, health scholars acknowledge bereavement as a determinant of population health. Some research suggests that childhood health is especially affected by the deaths of family members. Although most research has focused on losing a parent or sibling in childhood, more recently, scholarship has established grandparental death as a source of poor mental health. We know less, however, about whether grandparental death affects children biologically, potentially imprinting them in a way that is consequential for their physical health and development. In this study, we offer the first analysis of the association between grandparental loss and U.S. children's telomere length-a common biomarker that reflects cumulative stress exposure. We use data from the Future of Families and Child Wellbeing Study to study grandparental death and children's telomere length at around age 9. Boys' telomere length is not associated with grandparental death; however, girls, and in particular girls who did not co-reside with their grandmother around age 5, had shorter telomere lengths following the death of their grandmother compared to girls whose grandmothers were still alive. Specifically, a non-co-resident grandmother's recent death corresponds with 11 % shorter telomeres among girls (p < 0.001), which persists net of covariates. This study demonstrates that grandparental death is a unique health risk factor for children, emphasizing the need to consider grandparental death as an underappreciated source of childhood health disparities.},
}

@article {pmid40753954,
year = {2025},
author = {Kohlrausch, FB and de Oliveira, GDSR and de Mello Neto, CB and Fontenelle, LF},
title = {Shorter telomere length in obsessive-compulsive disorder: another evidence of neuroprogression?.},
journal = {Journal of psychiatric research},
volume = {189},
number = {},
pages = {513-520},
doi = {10.1016/j.jpsychires.2025.07.024},
pmid = {40753954},
issn = {1879-1379},
abstract = {BACKGROUND AND OBJECTIVES: There is evidence suggesting that obsessive-compulsive disorder (OCD) is a neuroprogressive illness. Telomeres, protective caps at the ends of chromosomes that prevent DNA damage, have been regarded as a potential biological marker associated with disease susceptibility and aging. In this study, we aimed to evaluate telomere length (TL) in OCD patients from Southeast Brazil.

METHODS: A total of 210 Brazilian individuals were included, 105 OCD patients and 105 control individuals. All participants were matched by age and sex between the two groups. DNA was extracted from buccal cells, and TL (T/S ratio) was assayed by multiplex quantitative polymerase chain reaction method (mmqPCR).

RESULTS: OCD patients exhibited significantly shorter TL than controls (p < 0.0001) in both sexes (males, p = 0.034 and females, p = 0.002). Also, TL correlated negatively with duration of illness, both in the total patients' sample (rho = -0.297, p = 0.003) and in the female OCD sample (rho = -0.341, p = 0.009). Age did not correlate with TL in controls, but it did correlate with TL in OCD subjects (p < 0.0001). Further, partial correlation analysis between TL and duration of illness, controlling for age, rendered the association non-significant. Age of onset and OCD symptom dimensions were not associated with TL in OCD patients.

CONCLUSIONS: OCD patients have shorter telomeres than controls, independently of sex. OCD female patients with longer illness duration have also shorter telomeres. Further studies are needed to clarify the mechanisms underlying this relationship and confirm telomere shortening as a promising biomarker of neuroprogression of OCD.},
}

@article {pmid40752890,
year = {2025},
author = {Eşel, G and Mermer, DB and Eker, ÖO and Amraliyev, A and Biçer, EÖ and Asdemir, A and Dündar, M and Eşel, E and İsmailoğulları, S},
title = {Telomere length in sleep disorders.},
journal = {Experimental gerontology},
volume = {},
number = {},
pages = {112851},
doi = {10.1016/j.exger.2025.112851},
pmid = {40752890},
issn = {1873-6815},
abstract = {BACKGROUND: Sleep and circadian rhythms are affected by aging. Although the relationship between sleep disorders and cellular aging has been demonstrated in some studies, it still remains unclear. Telomere length has been considered one of the sensitive biomarkers for aging in recent years. Studies investigating the relationship between sleep disorders and telomere length are limited and their results are inconsistent. This study aims to demonstrate telomer length in sleep disorders.

METHODS: The study sample consisted of 116 participants, 94 patients and 22 healthy participants. Patients groups comprised diagnosed with narcolepsy (N = 31), insomnia (N = 20), Restless Legs Syndrome (RLS) (N = 21), and Obstructive Sleep Apnea Syndrome (OSAS) (N = 22) according to ICSD-3 diagnostic criteria. All participants were aged between 18 and 55 and had no tobacco, alcohol, or substance dependence. Telomere lengths of the participants were measured using the rtPCR method.

RESULTS: When telomere lengths were compared across groups, no significant differences were observed between the healthy controls and any of the patient groups. However, among the patient groups, individuals with insomnia had significantly shorter telomere lengths compared to those with RLS (p = 0.014) and OSAS (p = 0.012) (F = 4.405; p = 0.002).

CONCLUSIONS: The finding that patients with insomnia exhibited shorter telomeres than those with RLS and OSAS suggests that insomnia may present a higher risk for age-related diseases and accelerated aging processes.},
}

@article {pmid40751243,
year = {2025},
author = {Shi, Y and Li, Y and Chen, R and Fang, N and Wang, M and Li, Z and Chen, Q and Shao, C and Lin, M and Huang, H},
title = {Peripheral and pulmonary telomere lengths in patients with non-idiopathic pulmonary fibrosis interstitial lung diseases.},
journal = {BMC pulmonary medicine},
volume = {25},
number = {1},
pages = {368},
pmid = {40751243},
issn = {1471-2466},
support = {2021-I2M-1-028//Chinese Academy of Medical Sciences Initiative for Innovative Medicine/ ; 2022-PUMCH-C-069//the National High Level Hospital Clinical Research Funding/ ; 2023ZD0509500//Noncommunicable Chronic Diseases-National Science and Technology Major Project/ ; 7242102//Beijing natural science foundation/ ; },
mesh = {Humans ; Male ; Female ; *Lung Diseases, Interstitial/genetics/blood ; Bronchoalveolar Lavage Fluid/cytology/chemistry ; Middle Aged ; Aged ; *Telomere ; Leukocytes, Mononuclear/metabolism ; Case-Control Studies ; Autoantibodies/blood ; *Telomere Homeostasis ; Immunosuppressive Agents/therapeutic use ; },
abstract = {INTRODUCTION: Telomere and telomerase abnormalities play critical roles in interstitial lung diseases (ILDs). This study aimed to explore the telomere lengths (TL) in cells in the peripheral blood and bronchoalveolar lavage fluid (BALF) of healthy individuals and patient with various types of non-idiopathic pulmonary fibrosis (IPF)-ILD and to evaluate the correlation between TL and clinical indicators.

METHODS: We enrolled 48 patients with ILDs and 21 control individuals who presented at our hospital from September 2023 to September 2024. The relative TL of genomic deoxyribonucleic acid (DNA) in peripheral blood mononuclear cells (PBMCs) and BALF macrophages were measured using quantitative polymerase chain reaction (qPCR).

RESULTS: Patients with non-IPF-FILD had significantly shorter PBMC TL than controls (p < 0.001) and non-F-ILD patients (p < 0.001). There was a linear correlation between the TL in cells in the BALF and peripheral blood. Compared with control individuals, patients with non-F-ILD also had no significant difference in TL in cells both in the PBMC and BALF. TL was strongly associated with the presence of autoantibodies (η[2] = 0.275, p = 0.012) and the use of immunosuppressants (η[2] = 0.246, p = 0.010).

CONCLUSIONS: The PBMC TL of non-IPF-FILD patients were significantly shorter than that of control and non-F-ILD patients. However, there was no significant difference in TL in cells in the BALF and peripheral blood between non-F-ILD patients and control individuals. TL were closely correlated with the presence of autoantibodies and treatment with immunosuppressants.},
}

Humans
Male
Female
*Lung Diseases, Interstitial/genetics/blood
Bronchoalveolar Lavage Fluid/cytology/chemistry
Middle Aged
Aged
*Telomere
Leukocytes, Mononuclear/metabolism
Case-Control Studies
Autoantibodies/blood
*Telomere Homeostasis
Immunosuppressive Agents/therapeutic use

@article {pmid40748758,
year = {2025},
author = {Khandagale, P and Sun, Y and Taniyama, D and Saha, S and Saha, LK and Pommier, Y},
title = {Topoisomerase IIIα controls alternative lengthening of telomeres.},
journal = {Cell reports},
volume = {44},
number = {8},
pages = {116066},
doi = {10.1016/j.celrep.2025.116066},
pmid = {40748758},
issn = {2211-1247},
abstract = {Alternative lengthening of telomeres (ALT) is a homologous recombination-dependent telomere elongation mechanism utilized by at least 10%-15% of all cancers. Here, we identify that the DNA topoisomerase, topoisomerase III⍺ (TOP3A), is enriched at the telomeres of ALT cells but not at the telomeres of telomerase (Tel)-positive cancer cells. We demonstrate that TOP3A stabilizes the shelterin complex in ALT cancer cell lines but not in Tel cells and that long non-coding telomeric-repeat containing RNA (TERRA) enrichment at telomeres depends on TOP3A. TOP3A also promotes the generation of single-stranded telomeric C-strand (ssTeloC) DNA, a recently discovered marker for ALT. Additionally, we find that inducing break-associated TOP3A-DNA-protein crosslinks in ALT cells suppresses TERRA enrichment and destabilizes the shelterin complex. Taken together, these observations uncover unexplored functions of TOP3A at ALT telomeres and suggest the potential of developing an ALT-specific cancer therapeutic strategy targeting TOP3A.},
}

@article {pmid40748434,
year = {2025},
author = {Kutasi, E and Chis, A and Vintan, MA and AlKhzouz, C and Văduva, DA and Cătană, A and Vulturar, R},
title = {Telomere Biology, Erosion, and Age-Related Conditions: Insights from Down Syndrome and Other Telomere-Associated Disorders.},
journal = {Molecular neurobiology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s12035-025-05245-1},
pmid = {40748434},
issn = {1559-1182},
abstract = {Telomeres play a crucial role in safeguarding DNA integrity. With each cell division, these protective structures undergo shortening, limiting the number of divisions to prevent improper genetic material distribution in aging cells. Senescent cells accumulate in tissues and contribute to age-related changes and decreased regeneration. Various genetic conditions are linked to premature aging and the early onset of age-related disorders. Down syndrome (DS), or chromosome 21 trisomy, is a relatively frequent aneuploidy, having an incidence of 1/1000-1/1100 newborns, and a major cause of intellectual disability. DS individuals exhibit a higher prevalence and earlier onset of age-related disorders, particularly Alzheimer's disease, due to the buildup of beta-amyloid. In DS individuals, telomere erosion occurs at an accelerated rate, caused by the overexpression of numerous genes, and it is associated with various factors, including obesity, inflammation, hormonal fluctuations, physical or emotional stress, higher levels of reactive oxygen species, and autoimmune disorders. Although telomere length in DS children is initially higher than in the general population, their telomeres experience a more rapid shortening process. Developing strategies that target molecular pathways linked to telomere erosion and telomerase activity could become a key point for the therapeutic management of DS individuals.},
}

@article {pmid40748226,
year = {2025},
author = {Mattis, N and Goncalves, T and Kim, K and Hammond, EM and Rose, AM},
title = {Silencing of SOD1 sensitises ATRX-deficient cells to camptothecin treatment through increased activity of the alternative lengthening of telomeres pathway.},
journal = {Human molecular genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/hmg/ddaf118},
pmid = {40748226},
issn = {1460-2083},
abstract = {The alternative lengthening of telomeres (ALT) pathway is a telomere maintenance mechanism that is driven by formation of DNA double-strand breaks at telomeres. ALT-positive malignancies often have mutational deletion of ATRX, but formation of DNA-protein complexes (DPCs) and elevated reactive oxygen species (ROS) also play a role in the induction of the ALT pathway. It has been recognised that excessive ALT activation can lead to rapid cell death, due to genome instability. Our objectives were to assess whether combining ROS-forming and DPC-forming treatments had a synergistic effect in ATRX-deficient cells. We found that SOD1 silencing was an effective method for inducing cell death in ATRX-deficient osteosarcoma cell lines; further, this approach was more effective in ATRX-null HeLa-LT than ATRX-wildtype cells. We also observed that dual treatment with DPC-forming chemotherapy (camptothecin) and SOD1 silencing led to a significantly higher level of DPCs, as well as signs of ALT pathway overactivity. Finally, our investigation demonstrated that pre-treatment of ATRX-null cells with shSOD1 significantly increased cellular sensitivity to camptothecin, with synergy between the two treatments. This research provides critical understanding to inform new treatment approaches-which might eventually improve survival for affected individuals, and reduce long-term effects, for survivors of ALT-positive malignancies.},
}

@article {pmid40745453,
year = {2025},
author = {Mohammadi, A and Jones, DT and Mohammadi, S and Heidari-Bateni, G and Frishman, WH and Aronow, WS},
title = {Telomere Dynamics in Cardiovascular Aging: From Molecular Mechanisms to Precision Medicine.},
journal = {Cardiology in review},
volume = {},
number = {},
pages = {},
pmid = {40745453},
issn = {1538-4683},
abstract = {Telomere attrition stands as a fundamental hallmark of cardiovascular aging, driving cellular senescence and dysfunction across endothelial, cardiomyocyte, and vascular smooth muscle compartments. This review systematically examines: (1) molecular mechanisms linking telomere shortening to oxidative stress (NOX2/PRDX1 axis), epigenetic dysregulation (subtelomeric methylation, H3K9me3 loss), and mitochondrial dysfunction; (2) clinical evidence positioning leukocyte telomere length and telomere-associated proteins (eg, TRF2, POT1) as predictive biomarkers for coronary artery disease, heart failure, and hypertension; and (3) emerging therapeutic strategies ranging from telomerase activation (TA-65, GRN510) to senolytic cocktails (dasatinib + quercetin) and CRISPR (regularly interspersed short palindromic reportsclustered regularly interspaced short palindromic repeats)-based editing (6-29% efficiency in Chinese hamster ovary models). The review further addresses methodological challenges in telomere measurement (quantitative polymerase chain reaction (PCR) vs Flow-FISH standardization) and proposes an integrated risk assessment model combining leukocyte telomere length, oxidative markers (AGEs/sRAGE ratio), and epigenetic clocks. Translationally, we discuss tissue-specific delivery systems to mitigate oncogenic risks of telomerase therapies while emphasizing mitochondrial-targeted approaches for telomere stabilization. This synthesis bridges basic telomere science with clinical cardiology, offering a roadmap for personalized vascular rejuvenation strategies.},
}

@article {pmid40741482,
year = {2024},
author = {Wilson, DG and Clatterbuck Soper, SF and Pineda, MA and Walker, RL and Meltzer, PS},
title = {Telomere interactions and structural variants in ALT cells revealed with TelSPRITE.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.11.22.624895},
pmid = {40741482},
issn = {2692-8205},
abstract = {Acquisition of a telomere maintenance mechanism is essential for cancer cells. In a minority of tumors, telomeres are lengthened via Alternative Maintenance of Telomeres (ALT), a telomerase-independent pathway based on homologous recombination. ALT tumors have heavily rearranged genomes with many structural variants containing telomere repeats. To better understand the genetic evolution of these tumors, we seek to determine if certain genomic loci tend to spatially associate with telomeres in ALT and are especially liable to experience telomere recombination events as a result. Assays that reveal close spatial associations between genomic loci, such as SPRITE and Hi-C, have enabled extensive exploration of genomic spatial organization. However, as analysis pipelines for these next-generation sequencing-based assays typically discard reads aligning to repetitive elements, little is known about the spatial arrangement of telomeres and other repetitive loci in the nucleus. Here, we present TelSPRITE, a novel approach to extracting telomere contact frequencies from SPRITE data. We identify reads containing telomere repeats and sort them into a single bin, quantifying spatial contacts between the telomere bin and the rest of the genome. Our analysis reveals a strong dependency of telomere contact frequency on chromosomal distance from the telomere, consistent with the known effect of linear distance on 3-dimensional spatial contacts. Telomere contacts are also strongly enriched near centromeres, a phenomenon that may be reflective of spatial clustering of heterochromatic regions. ALT cell lines are globally enriched for telomere content and display distinctive intrachromosomal spikes in telomere contact frequency. Our customized analysis of long read sequencing data suggests that loci with high telomere contact frequencies represent structural variants containing telomere repeats in ALT cells. Collectively, our results demonstrate general principles of telomeric spatial organization while also profiling the spectrum of genomic rearrangements in ALT cells.},
}

@article {pmid40726990,
year = {2025},
author = {Mesli, F and Philippot, Q and El Husseini, K and Bunel, V and Kannengiesser, C and Debray, MP and Guyard, A and Crestani, B and Ba, I and Borie, R},
title = {Telomere biology disorders in lung transplantation: Clinical challenges and management strategies.},
journal = {JHLT open},
volume = {9},
number = {},
pages = {100333},
pmid = {40726990},
issn = {2950-1334},
abstract = {Telomeres, repetitive DNA sequences at the ends of chromosomes, play a crucial role in maintaining genomic stability. In recent years, their significance in lung transplantation has gained growing attention. Shortened telomeres-whether due to inherited telomeropathies or acquired attrition-have emerged as a risk factor for various pulmonary diseases, particularly pulmonary fibrosis, which is a leading indication for lung transplantation. This review provides a comprehensive overview of current knowledge on the impact of short telomeres in lung transplant recipients, encompassing pre-transplant assessment and post-transplant outcomes. Patients with telomere-biology disorder present unique clinical challenges. Before transplantation, they may exhibit extra-pulmonary manifestations such as bone marrow dysfunction, hepatic abnormalities, precipitation to develop cancer, all of which necessitate a tailored evaluation and multidisciplinary management. After transplantation, these patients appear to be at increased risk of complications, including drug-related hematologic toxicity, bone marrow failure, and heightened susceptibility to infections. The review emphasizes the importance of identifying patients with telomere biology disorders early in the transplant process and supports the incorporation of telomere length testing in selected populations. Furthermore, it highlights the need for adjusted immunosuppressive strategies and closer surveillance in this vulnerable population. Ultimately, the authors advocate for prospective, multicenter studies aimed at refining the prognostic value of telomere length and guiding evidence-based, individualized transplant strategies for patients with telomere biology disorders related interstitial lung diseases.},
}

@article {pmid40725011,
year = {2025},
author = {Udroiu, I and Sgura, A},
title = {Alternative Lengthening of Telomeres: The Need for ATRX Mutations Is Lineage-Dependent.},
journal = {International journal of molecular sciences},
volume = {26},
number = {14},
pages = {},
pmid = {40725011},
issn = {1422-0067},
mesh = {Humans ; *X-linked Nuclear Protein/genetics/metabolism ; *Telomere Homeostasis/genetics ; *Mutation ; *Telomere/genetics/metabolism ; Cell Line, Tumor ; *Cell Lineage/genetics ; },
abstract = {During carcinogenesis, cells must acquire a telomere maintenance mechanism in order to avoid telomere shortening-induced replicative senescence. While most tumors activate telomerase, a minority of them employ a recombinational mechanism called Alternative Lengthening of Telomeres (ALT). One of the most investigated features is the association between ALT and ATRX mutations, since this has been shown to be the gene with the highest rate of mutations among ALT tumors. However, most of these studies, and in particular, mechanistic studies in vitro, have been carried out on mesenchymal tumors (sarcomas). In the present study, using genomic and expression data from the DepMap portal, we identified several non-mesenchymal ALT cell lines, and we compared the incidence of ATRX and other gene mutations between ALT cell lines of different origins (mesenchymal, neural, epithelial, hematopoietic). We confirmed that ATRX is frequently mutated in mesenchymal and neural ALT cell lines but not in epithelial ones. Our results showed that mutations of ATRX or other proteins involved in the maintenance of telomere integrity are needed for ALT activation in all cell types, and ATRX is preferentially mutated in mesenchymal ALT cells. Besides a more precise interpretation of the role of ATRX loss in ALT establishment, we proposed a model in which mutation of this gene impairs differentiation in mesenchymal and neural cells (but not in epithelial ones). Therefore, we explained the high incidence of ATRX mutations in mesenchymal and neural tumors with the fact that they both trigger ALT and impair differentiation, thus promoting two steps at once in the process of carcinogenesis.},
}

Humans
*X-linked Nuclear Protein/genetics/metabolism
*Telomere Homeostasis/genetics
*Mutation
*Telomere/genetics/metabolism
Cell Line, Tumor
*Cell Lineage/genetics

@article {pmid40723168,
year = {2025},
author = {Rembiałkowska, N and Sędzik, M and Kisielewska, M and Łuniewska, W and Sebastianka, K and Molik, K and Skinderowicz, K and Kuźnicki, J and Tunikowska, J and Kulbacka, J},
title = {Telomere Maintenance and DNA Repair: A Bidirectional Relationship in Cancer Biology and Therapy.},
journal = {Cancers},
volume = {17},
number = {14},
pages = {},
pmid = {40723168},
issn = {2072-6694},
support = {SUBZ.D260.25.027//Wroclaw Medical Uniwersity/ ; },
abstract = {Telomeres are repetitive DNA sequences at the ends of chromosomes that protect against genomic instability and prevent unwanted DNA damage responses. In most somatic cells, telomeres progressively shorten with each division, limiting cellular lifespan. However, cancer cells bypass this limitation by activating telomerase or the alternative lengthening of telomeres, enabling unchecked proliferation and tumor progression. This review examines the molecular mechanisms underlying telomere maintenance and their intricate relationship with DNA repair pathways. We discuss how telomere-associated proteins regulate genomic stability and explore therapeutic strategies targeting telomerase and alternative lengthening of telomeres. Challenges such as resistance mechanisms and off-target effects are also considered, highlighting the need for precision approaches in telomere-based cancer therapies.},
}

@article {pmid40723068,
year = {2025},
author = {Campos-Sánchez, I and Navarrete-Muñoz, EM and Barber-Valles, JX and Martens, DS and Riaño-Galán, I and Irizar, A and Llop, S and Guxens, M and Rodríguez-Dehli, C and Babarro, I and Lozano, M and Vrijheid, M and Nawrot, T and Valera-Gran, D},
title = {Telomere Length and Emotional and Behavioral Problems in Children from the Prospective Birth Cohort INfancia y Medio Ambiente (INMA) Study.},
journal = {Children (Basel, Switzerland)},
volume = {12},
number = {7},
pages = {},
pmid = {40723068},
issn = {2227-9067},
support = {PI18/00825; FIS-PI042018; FIS-PI09/02311; FIS-PI13/02429; FIS-PI18/00909; FIS-PI06/0867; FIS-PI09/00090; FIS-PI13/02187; FIS-PI18/01142; FIS-PI18/01237; G03/176; CB06/02/0041; PI041436; PI081151; PI12/01890; CP13/00054; PI15/00118 ;//Instituto de Salud Carlos III/ ; FPU21/01323//ministry of universities of Spain/ ; 2005111093; 2009111069; 2013111089; 2015111065;2018111086//Department of Health of the Basque Government/ ; DFG06/002; DFG08/001; DFG15/221; DFG 89/17//Provincial Government of Gipuzkoa/ ; 2009 SGR 501; 2014 SGR 822//Government of Catalonia/ ; 090430//Fundació La marató de TV3/ ; SAF2012-32991//Spanish Ministry of Economy and Competitiveness/ ; 1262C0010//Agence Nationale de Securite Sanitaire de l'Alimentation de l'Environnement et du Travail/ ; 261357;308333; 603794;634453//EU Commission/ ; GVA/2021/191; CIAICO/2021/132; BEST/2020/059; AICO 2020/285; AICO/2021/182; CIDEGENT/2019/064//Generalitat Valenciana/ ; PI11/01007; PI11/02591; PI11/02038; PI12/00610; PI13/1944; PI13/2032; PI14/00891; PI14/01687; PI16/1288; PI17/00663; PI19/1338; P 23/1578//Instituto de Salud Carlos III/ ; CP11/00178; CP15/00025; MSII16/00051; MS20/0006//Miguel Servet-FEDER/ ; MS21-133; CAS21/00008; NextGeneration EU//Spanish Ministry of Universities/ ; PNI22_CGE45//Consejo General de Enfermería/ ; UGP 15-230; UGP-15-244; UGP-15-249//FISABIO/ ; },
abstract = {Background/Objectives: This study aimed to examine the association between leukocyte telomere length (TL) measured at ages 4 and 8 and emotional and behavioral problems at age 8. We also explored whether changes in leukocyte TL between ages 4 and 8 were associated with outcomes. Methods: Data were obtained from a population-based birth cohort and included 647 children with TL at age 4 and emotional and behavioral assessments at age 8, 673 with TL and outcomes at age 8, and 315 with TL measured at both ages. TL was determined using quantitative PCR on blood samples and converted into z-scores for analysis. Emotional and behavioral problems-including internalizing, externalizing, and total difficulties-were assessed using the Strengths and Difficulties Questionnaire. Regression models were conducted using zero-inflated and negative binomial, adjusting for sociodemographic and lifestyle covariates. Results: No statistically significant associations were observed between leukocyte TL at ages 4 or 8, or TL changes over this period, and emotional and behavioral outcomes at age 8. Conclusions: Although no significant associations were found, further longitudinal research is warranted to clarify the role of TL as a potential psychobiomarker of emotional and behavioral disorders in childhood.},
}

@article {pmid40721267,
year = {2025},
author = {Pistucci, R and Cascone, I and Iannuzzi, A and Albarella, S and Kowal-Mierzwa, W and Zannotti, M and Iannuzzi, L and Parma, P},
title = {Comparative analysis of cattle (Bos taurus, 2n = 60) and river buffalo (Bubalus bubalis, 2n = 50) genome assemblies reveals two evolutionary conserved inversions and invalid centromere-telomere orientation of some autosomes.},
journal = {Animal genetics},
volume = {56},
number = {4},
pages = {e70031},
pmid = {40721267},
issn = {1365-2052},
mesh = {Animals ; *Buffaloes/genetics ; Cattle/genetics ; *Chromosome Inversion ; Centromere/genetics ; *Telomere/genetics ; *Genome ; *Evolution, Molecular ; In Situ Hybridization, Fluorescence ; },
abstract = {This study investigates autosome evolution between river buffalo (Bubablus bubalis, BBU) and cattle (Bos taurus, BTA), two closely related species within the Bovidae family. Despite differences in chromosome numbers (2n = 60 in cattle and 2n = 50 in river buffalo), previous cytogenetic studies have shown high autosome similarity. However, standard banding techniques have limitations in detecting small-scale genomic rearrangements. Using molecular comparisons, this study identifies two previously undetected chromosomal inversions: a 30-Mb inversion on BBU7 (compared to BTA6) and a 4-Mb inversion on BBU14 (compared to BTA13). These findings were validated through bioinformatics analyses (genomic alignments and BLAST searches) and confirmed via fluorescence in situ hybridization technique. In addition, it has been shown that several river buffalo chromosomes are shown inverted in the genome assembly considered in this study (NDDB_SH_1). The study highlights that autosome evolution in Bovidae involves not only centric fusions but also cryptic intra-chromosomal rearrangements. These results contribute to a deeper understanding of genome evolution in closely related species and demonstrate the importance of high-resolution molecular techniques in uncovering hidden genomic changes.},
}

Animals
*Buffaloes/genetics
Cattle/genetics
*Chromosome Inversion
Centromere/genetics
*Telomere/genetics
*Genome
*Evolution, Molecular
In Situ Hybridization, Fluorescence

@article {pmid40716322,
year = {2025},
author = {Soniat, MM and Myler, LR},
title = {Using the safety scissors: DNA resection regulation at DNA double-strand breaks and telomeres.},
journal = {DNA repair},
volume = {152},
number = {},
pages = {103876},
doi = {10.1016/j.dnarep.2025.103876},
pmid = {40716322},
issn = {1568-7856},
abstract = {DNA resection is a universal process in genome maintenance by which one strand of DNA is degraded, leaving the other strand intact. This sometimes highly processive process is critical for many forms of DNA damage repair, replication-coupled repair, meiotic recombination, and telomere maintenance. Therefore, resection must be tightly regulated to prevent genome instability and promote faithful and accurate repair. Here, we review what is known about how resection functions and how it is controlled, using DNA double-strand break repair and telomere maintenance as examples. We address how resection is regulated in three independent steps: resection initiation, long-range processing, and termination. By addressing these mechanisms in the context of both pathways, we attempt to provide an overview of the similarities as well as the outstanding questions regarding how this robust process is regulated.},
}

@article {pmid40720841,
year = {2025},
author = {Bian, C and Huan, R and Shi, Q},
title = {Telomere-to-telomere chromosome-scale genome assemblies of black and golden koi carp variants support construction of an ancient karyotype of Cypriniformes.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf073},
pmid = {40720841},
issn = {2047-217X},
support = {2023YFE0205100//National Key Research and Development Program of China/ ; 2022YFE0139700//National Key Research and Development Program of China/ ; 000,001,032,215//Research Initiation Fund for Young Faculty Members at Shenzhen University/ ; },
mesh = {Animals ; *Telomere/genetics ; *Karyotype ; *Genome ; *Carps/genetics/classification ; Phylogeny ; Evolution, Molecular ; Chromosomes/genetics ; *Cypriniformes/genetics ; Genomics/methods ; },
abstract = {BACKGROUND: Koi carp, a variant of the common carp, is one of the most popular ornamental fish. Its genomic resources can help us better understand chromosome evolution and color phenotypes in cyprinid fish.

RESULTS: We constructed telomere-to-telomere chromosome-level genome assemblies for 2 koi carp variants (black and golden) by integrating MGI, PacBio HiFi, ONT, and Hi-C sequencing technologies. Haplotypic genomes comprised 50 chromosomes with 100 and 99 telomeres, respectively, with BUSCO results showing at least 98.8% completeness. We annotated a total of 55,023 and 54,569 protein-coding genes for black and golden koi carps, respectively, with over 96% assigned functional roles. Repetitive sequences occupy an estimated 636 Mb (41%) of the genomes. With phylogenetic analysis, we predict the koi carp variants to have split 5.3 million years ago, and we constructed an ancient karyotype of 25 ancestral chromosomes to reveal 9 major chromosomal rearrangements.

CONCLUSIONS: Our study offers genome assemblies capable of predicting an ancient karyotype of Cypriniformes, with genomic resources available for in-depth investigations into diverse skin coloration in koi and other cypriniforms.},
}

Animals
*Telomere/genetics
*Karyotype
*Genome
*Carps/genetics/classification
Phylogeny
Evolution, Molecular
Chromosomes/genetics
*Cypriniformes/genetics
Genomics/methods

@article {pmid40714838,
year = {2025},
author = {Shen, L and Yi, C and Liu, Y and Han, F and Feng, J},
title = {Two complete telomere-to-telomere Medicago genomes reveal the landscape and evolution of centromeres.},
journal = {Molecular plant},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.molp.2025.07.016},
pmid = {40714838},
issn = {1752-9867},
abstract = {In this study, we report two gap-free genome assemblies of Medicago truncatula A17 and Medicago littoralis R108 generated using long-read sequencing. The assemblies reveal distinct centromere compositions, highlighting lineage-specific satellite repeat evolution and providing valuable resources for legume functional genomics and centromere biology.},
}

@article {pmid40714351,
year = {2025},
author = {Carvalho, BG and Ribeiro, AA and da Mota, JCNL and Carvalho, LM and Nicoletti, CF},
title = {Integrating biological age, epigenetic clocks, and telomere length in precision nutrition strategies for chronic disease management: Potential frameworks and ongoing challenges.},
journal = {Nutrition research (New York, N.Y.)},
volume = {140},
number = {},
pages = {135-160},
doi = {10.1016/j.nutres.2025.06.010},
pmid = {40714351},
issn = {1879-0739},
abstract = {Precision nutrition is emerging as a transformative strategy for optimizing health, particularly in the context of biological aging and chronic disease prevention. This review aims to examine how biological age markers-specifically telomere length and epigenetic clocks-can be integrated into precision nutrition frameworks to personalize interventions, enhance chronic disease management, and support healthy aging. Telomere length is a widely studied biomarker of aging and chronic disease risk, while epigenetic clocks, based on DNA methylation patterns, offer complementary insights into biological age, gene expression, and disease susceptibility. Nutritional interventions rich in antioxidants, omega-3 fatty acids, polyphenols, B vitamins, and anti-inflammatory compounds have shown potential to modulate these biomarkers, supporting cellular health and delaying aging processes. In addition, lifestyle factors such as physical activity, stress management, and adequate sleep play critical roles in maintaining telomere integrity and epigenetic stability. However, challenges remain in translating these biomarkers into clinical practice. Importantly, variability is not the only barrier; most of these biomarkers still lack clinical validation, and there is no consensus on standardized protocols or reference values that would support their routine application in healthcare. Current guidelines recommend combining telomere length and epigenetic age with other molecular markers, such as multi-omics data, within integrative biological age assessment approaches. Nevertheless, translating this approach into clinical practice will require overcoming significant limitations, including the validation of biomarkers, standardization of measurement techniques, cost-effectiveness, and the development of clear clinical guidelines. Continued research is essential to confirm their predictive value and practical utility in precision nutrition strategies aimed at promoting healthy aging and preventing chronic diseases.},
}

@article {pmid40708199,
year = {2025},
author = {Yu, C and Kang, EY and Wang, D and Liang, Y and Swiderski, P and Feng, Y and Li, H and Synold, T and Forman, S and Kwak, L and Kortylewski, M},
title = {Cell-Selective Telomere Damage by Thiopurine-Based Oligonucleotide for Diffuse Large B-cell Lymphoma Immunotherapy.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2025.07.029},
pmid = {40708199},
issn = {1525-0024},
abstract = {Telomerase (TERT) is an enzyme involved in maintaining telomere length in diffuse large B-cell lymphoma (DLBCL). Previous attempts to target TERT[+] cancers faced challenges, including the delayed clinical responses and on-target/off-tumor toxicities. Here, we present a DLBCL-targeted oligonucleotide designed to deliver a synthetic TERT substrate, 6-thio-2'-deoxy-guanosine (6tdG), damaging telomeres and triggering apoptosis. In vitro, 6tdG-oligonucleotides (6tdGOs) were selectively cytotoxic to TERT[+] DLBCL cells without affecting activated T-cells or non-malignant TERT[-] cells. Repeated intravenous administration of 6tdGO, but not 6tdG nucleoside, had significant antitumor effects against xenotransplanted human DLBCL models and syngeneic Eμ-myc/15A lymphoma in mice. In immunocompetent mice, treatment with 6tdGO induced systemic, lymphoma-specific and CD8 T-cell-mediated antitumor immune responses. The abscopal effects of 6tdGO were abolished in mice lacking expression of Sting1 or Ifnar1 but not Trl9. These findings suggest that 6tdGO-induced lymphoma cell death triggered STING-mediated type-I IFN signaling, thereby promoting recruitment/activation of CD8 T-cells. Importantly, the repeated 6tdGO treatments were well-tolerated in humanized hCD34/NOG mice. Except for the reduced percentage of human B-cells, 6tdGO did not decrease the numbers of hematopoietic stem cells, myeloid cells, or T-cells. Overall, 6tdGO offers an effective and safer strategy against aggressive TERT[+] DLBCL with potential to activate T-cell based antitumor immunity.},
}

@article {pmid40707444,
year = {2025},
author = {Mattarocci, S and Baconnais, S and Roisné-Hamelin, F and Pobiega, S and Alibert, O and Morin, V and Deshayes, A and Veaute, X and Ropars, V and Chevreuil, M and Mehringer, J and Busso, D and Mazon, G and Fernandez Varela, P and Le Cam, É and Charbonnier, JB and Cuniasse, P and Marcand, S},
title = {Restriction of Ku translocation protects telomere ends.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6824},
pmid = {40707444},
issn = {2041-1723},
mesh = {*Telomere/metabolism/genetics/ultrastructure ; *DNA End-Joining Repair ; Shelterin Complex/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/metabolism/genetics ; *Telomere-Binding Proteins/metabolism/genetics ; *Ku Autoantigen/metabolism/genetics ; DNA Breaks, Double-Stranded ; DNA-Binding Proteins/metabolism/genetics ; Cryoelectron Microscopy ; Protein Binding ; Transcription Factors ; },
abstract = {Safeguarding chromosome ends against fusions via nonhomologous end joining (NHEJ) is essential for genome integrity. Paradoxically, the conserved NHEJ core factor Ku binds telomere ends. How it is prevented from promoting NHEJ remains unclear, as does the mechanism that allows Ku to coexist with telomere-protective DNA binding proteins, Rap1 in Saccharomyces cerevisiae. Here, we find that Rap1 directly inhibits Ku's NHEJ function at telomeres. A single Rap1 molecule near a double-stand break suppresses NHEJ without displacing Ku in cells. Furthermore, Rap1 and Ku form a complex on short DNA duplexes in vitro. Cryo-EM shows Rap1 blocks Ku's inward translocation on DNA - an essential step for NHEJ at DSBs. Nanopore sequencing of telomere fusions confirms this mechanism protects native telomere ends. These findings uncover a telomere protection mechanism where Rap1 restricts Ku's inward translocation. This switches Ku from a repair-promoting to a protective role preventing NHEJ at telomeres.},
}

*Telomere/metabolism/genetics/ultrastructure
*DNA End-Joining Repair
Shelterin Complex/metabolism
*Saccharomyces cerevisiae/genetics/metabolism
*Saccharomyces cerevisiae Proteins/metabolism/genetics
*Telomere-Binding Proteins/metabolism/genetics
*Ku Autoantigen/metabolism/genetics
DNA Breaks, Double-Stranded
DNA-Binding Proteins/metabolism/genetics
Cryoelectron Microscopy
Protein Binding
Transcription Factors

@article {pmid40707108,
year = {2025},
author = {Cardozo, AG and Castrogiovanni, DC and Parisi, JM and Bolzán, AD},
title = {Bleomycin induces short-term telomere fragility in Epstein-Barr virus-transformed human lymphoblastoid cells.},
journal = {Mutation research. Genetic toxicology and environmental mutagenesis},
volume = {905},
number = {},
pages = {503877},
doi = {10.1016/j.mrgentox.2025.503877},
pmid = {40707108},
issn = {1879-3592},
mesh = {Humans ; *Bleomycin/toxicity/pharmacology ; *Herpesvirus 4, Human/physiology ; *Telomere/drug effects/genetics ; Cell Line, Transformed ; *Lymphocytes/drug effects/virology ; Chromosome Aberrations/chemically induced/drug effects ; Cell Transformation, Viral ; *Antibiotics, Antineoplastic/toxicity ; In Situ Hybridization, Fluorescence ; },
abstract = {The induction of telomere dysfunction-related chromosomal aberrations by the radiomimetic antibiotic bleomycin (BLM) was studied in human lymphoblastoid cells immortalized with the Epstein-Barr virus (EBV). To this end, an EBV-induced lymphoblastoid cell line (T-37) was exposed to increased concentrations of BLM (10-100 µg/mL) for 2 h at 37ºC, and telomere aberrations were analyzed 24 h (first mitosis) after treatment using PNA-FISH with pan-telomeric plus pan-centromeric probes. Telomere signal duplications (TSD) increased significantly in BLM-exposed cells (p < 0.01), although the concentration-response relationship was non-linear. Most of the induced TSD (95-99 %) were of chromatid-type. No induction of telomere signal loss, telomere fusions or telomere associations by BLM was observed in T-37 cells. These findings show that BLM induces short-term telomere dysfunction in EBV-transformed human lymphoblastoid cells in the form of TSD (which implies telomere fragility) and suggest that these effects mainly occur during the G2 stage of the cell cycle. The persistence of this type of aberrations in the long-term in EBV-induced lymphoblastoid cells and other human cells exposed to BLM may be of medical relevance. Telomere fragility induced by BLM could promote genomic instability, which might contribute to the development of secondary tumors in patients undergoing chemotherapy based on this compound. Consequently, our study raises concerns about the potential long-term genomic effects of BLM in treated patients and suggests that the analysis of TSD could be a useful biomarker for detecting BLM-induced telomere dysfunction in human cells.},
}

Humans
*Bleomycin/toxicity/pharmacology
*Herpesvirus 4, Human/physiology
*Telomere/drug effects/genetics
Cell Line, Transformed
*Lymphocytes/drug effects/virology
Chromosome Aberrations/chemically induced/drug effects
Cell Transformation, Viral
*Antibiotics, Antineoplastic/toxicity
In Situ Hybridization, Fluorescence

@article {pmid40702545,
year = {2025},
author = {Gemmati, D and Scarpellini, F and Salvatori, F and D'Aversa, E and Marci, R and Capucci, R and Antonica, B and Grisafi, M and Turato, E and Vargas, JV and Secchiero, P and Zauli, G and Singh, AV and Tisato, V},
title = {LINE-1 Methylation sustains telomere length in pregnant women: effects on pregnancy failure.},
journal = {Clinical epigenetics},
volume = {17},
number = {1},
pages = {130},
pmid = {40702545},
issn = {1868-7083},
support = {FAR and FIRD//Local Ferrara University Grants/ ; FAR and FIRD//Local Ferrara University Grants/ ; },
mesh = {Humans ; Female ; Pregnancy ; *DNA Methylation ; Adult ; *Long Interspersed Nucleotide Elements/genetics ; *Abortion, Spontaneous/genetics ; *Telomere/genetics ; Maternal Age ; Epigenesis, Genetic ; Telomere Homeostasis/genetics ; Young Adult ; Risk Factors ; },
abstract = {BACKGROUND: Pregnancy loss is one of the most common adverse events during the first weeks of gestation, and the incidence increases with maternal age and in presence of selected risk factors. Nonetheless, no risk factors have been identified in most cases, considering these cases unexplained. Fertility rate decreases as maternal age increases and epigenetic age-dependent conditions may favor miscarriage. DNA methylation and telomere length are informative of aging and cell senescence, and their assessment has been evaluated as predictors of successful pregnancy.

RESULTS: Telomere length (TL; T/S) and LINE-1 methylation (LINE-1; %) have been assessed in a cohort of 242 pregnant women by comparing spontaneous early miscarriage (EPL, n = 129) with voluntary interruption (VPI, n = 113). Telomere size and LINE-1 methylation rate drastically decreased as the age of women increased (P < 0.000001) with EPL group having lower values (T/S: 322.6 ± 142.0 versus 455.0 ± 290.6; P < 0.000001 and LINE-1 %: 81.66 ± 4.2 versus 86.01 ± 3.7; P < 0.000001) also characterized by stronger age-dependent lowering compared to VPI (P = 0.00035 and P < 0.000001, respectively). A global improvement in TL was observed as LINE-1 methylation rate increased, and it was more evident in EPL than in VPI (P < 0.000001). Focusing on the area below the 25th percentile of TL and LINE-1 % distribution, an overrepresentation of EPL cases was observed (P < 0.000001). On the contrary, VPI controls were dramatically overrepresented (P < 0.000001) in the area above the respective 75th percentiles. The mutual comparison of the number of EPL and VPI in these two extreme areas (EPL/VPI(<25th) = 3.12 versus EPL/VPI(>75th) = 0.32) yielded a significant risk of early pregnancy failure when women carried both risk conditions, low TL and LINE-1 methylation (OR = 9.70, 3.94-23.72; P < 0.0001). The intracase analyses ascribed to recurrent EPL cases even higher risks (OR = 10.5, 3.6-29.5; P < 0.0001) and a risk dosage effect stratification recognized to low methylation highest odds than that of short telomeres (OR = 4.44, 2.45-8.03; P < 0.0001 and OR = 2.26, 1.26-4.04; P = 0.005, respectively).

CONCLUSIONS: Overall, this suggests a combined effect of short telomeres and low methylation in phenotype worsening and a significant role of methylation in sustaining telomere size. These data support the hypothesis that different levels of DNA methylation may capture different biological mechanisms underlying telomere dynamics and dysfunctions and chromatin organization. Therefore, the concomitant assessment of telomere, methylation and their mutual interactions may be a novel strategy to translate the classical informative biomarkers of aging in the field of human reproduction.},
}

Humans
Female
Pregnancy
*DNA Methylation
Adult
*Long Interspersed Nucleotide Elements/genetics
*Abortion, Spontaneous/genetics
*Telomere/genetics
Maternal Age
Epigenesis, Genetic
Telomere Homeostasis/genetics
Young Adult
Risk Factors

@article {pmid40702442,
year = {2025},
author = {Guo, W and Bencivenga, L and Zanforlini, BM and Curreri, C and Ferrara, MC and Maisano, B and Tinelli, L and Ceparano, LA and Merenda, R and Cosma, C and Manfron, L and Gentili, N and Sturani, S and Cardi, M and Campion, A and Berardi, B and Lombardi, M and D'Aversa, E and Salvatori, F and Tisato, V and Vargas, JV and Femminella, GD and Gemmati, D and Sergi, G and Bellelli, G and Mazzola, P and Trevisan, C and Volpato, S and , },
title = {Effect of infections, DNA methylation and telomere length on frailty trajectories in hospitalized older patients: the INFRAGEN study protocol.},
journal = {BMC geriatrics},
volume = {25},
number = {1},
pages = {545},
pmid = {40702442},
issn = {1471-2318},
mesh = {Humans ; Aged ; *DNA Methylation/physiology ; Prospective Studies ; *Frailty/genetics/diagnosis/epidemiology ; *Hospitalization/trends ; Male ; Female ; Aged, 80 and over ; Italy/epidemiology ; *Infections/genetics/epidemiology ; Geriatric Assessment/methods ; *Telomere ; *Frail Elderly ; *Communicable Diseases/genetics ; *Telomere Homeostasis/physiology ; },
abstract = {BACKGROUND: Infectious diseases are among the most common causes of hospitalization in older adults and may lead to a high burden on the individual's health and healthcare system. However, it is unclear whether and to which extent these events might affect frailty, fastening its development or hampering its reversion. The aims of the INFRAGEN project are 1) to assess the impact of acute infections on frailty trajectories in older inpatients, and 2) to evaluate the modifying effect of sociodemographic, clinical, functional, and genetic/epigenetic factors on that association.

METHODS: INFRAGEN is a multicenter prospective observational study that will be conducted in the acute Geriatric Units of four Italian centers (Ferrara, Padova, Monza, and Napoli). The project will involve individuals aged ≥ 70 with no or mild-to-moderate pre-admission frailty (Clinical Frailty Scale [CFS] < 6) and diagnosis of acute infectious diseases at the time of hospital admission or during hospitalization. For each participant, we will record data concerning the multidimensional geriatric assessment and the type and severity of infectious diseases (diagnosed according to ICD-9 codes). Blood samples will be collected to assess Global DNA methylation, Leukocyte Telomere Length (LTL), and levels of circulating markers associated with biological processes related to frailty (inflammatory state, dysmetabolism, brain modifications, and oxidative stress). Frailty status will be evaluated through the CFS and Frailty Index at admission (referring to the 2 weeks before hospitalization), hospital discharge, and after 3 months. In a subsample, genetic/epigenetic analyses will also be performed at the 3-month follow-up.

DISCUSSION: INFRAGEN will contribute to exploring the complex pathophysiologic mechanisms of frailty in the context of infections in older adults through a translational approach.

TRIAL REGISTRATIONS: NCT06430073 (ClinicalTrials.gov); Registration date: 2024-05-28.},
}

Humans
Aged
*DNA Methylation/physiology
Prospective Studies
*Frailty/genetics/diagnosis/epidemiology
*Hospitalization/trends
Male
Female
Aged, 80 and over
Italy/epidemiology
*Infections/genetics/epidemiology
Geriatric Assessment/methods
*Telomere
*Frail Elderly
*Communicable Diseases/genetics
*Telomere Homeostasis/physiology

@article {pmid40699672,
year = {2025},
author = {Apetroaei, MM and Baliou, S and Ioannou, P and Fragkiadaki, P and Ștefan, G and Nedea, MII and Burcea-Dragomiroiu, GT and Velescu, BȘ and Docea, AO and Udeanu, DI and Tsatsakis, A and Arsene, AL},
title = {The Hallmarks of Ageing in Human Immunodeficiency Virus Infection and the Impact of Antiretroviral Therapy on Telomeres: A Molecular Perspective.},
journal = {Current issues in molecular biology},
volume = {47},
number = {4},
pages = {},
doi = {10.3390/cimb47040273},
pmid = {40699672},
issn = {1467-3045},
abstract = {Ageing is a complex and unavoidable physiological process which, in simple terms, consists of a progressive deterioration in the functionality of cells, tissues and organs, culminating in an increased risk of developing chronic pathologies. Telomeres, the repetitive nucleotide structures at the end of chromosomes, ensure genomic integrity and modulate cellular senescence. The progressive shortening of telomere length with each cell division directly correlates with an increased susceptibility to developing chronic pathologies. However, this shortening, normally physiological and inevitable, can be markedly accelerated in the presence of chronic infections, such as HIV-1 infection, by sustained and continuous activation of the immune system, chronic inflammation, generation of oxidative stress, or direct alterations produced by viral proteins. Thus, in this narrative review, we discuss the 12 hallmarks of ageing in the context of HIV-1 infection, as understanding the molecular changes induced by HIV-1 through these well-established pillars could provide a holistic approach to the management of HIV-positive patients. At the same time, considering that telomeres are at the centre of all these changes, an assessment of the impact of antiretroviral therapy on telomere length is necessary to guide clinical decisions. The ultimate goal of this research is to develop personalised therapies to increase the quality of life and health outcomes of HIV patients.},
}

@article {pmid40699549,
year = {2025},
author = {Yan, K and Zhang, H and Han, G and Kong, R and Zhao, Y},
title = {Mass In Situ Hybridization Enables Mass Cytometry to Detect Telomere Length.},
journal = {Analytical chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.analchem.5c01665},
pmid = {40699549},
issn = {1520-6882},
abstract = {Single-cell resolution detection of DNA sequences is crucial for advancing our understanding of cellular differentiation and disease mechanisms. Mass cytometry has had a transformative impact on single-cell protein analysis; however, the potential of mass cytometry in genomics remains limited due to the inability to integrate DNA sequence detection. Bridging this gap is essential to expanding the capabilities of mass cytometry for comprehensive genomic and proteomic studies. In this work, we presented a novel mass in situ hybridization (MISH) strategy that enables the detection of specific DNA sequences─telomeres at single-cell resolution. At first, we synthesized a dendritic oligomer chelated with holmium (Ho), which had enough sensitivity and proper molecular size, and then conjugated it with a high-specificity telomere oligo-DNA probe containing the (AATCCC)3 sequence, a short complementary nucleic acid sequence of telomere. Finally, we successfully applied MISH to detect the telomere length via mass cytometry and imaging mass cytometry (IMC). Our method establishes the first successful strategy for telomere length detection via mass cytometry, marking a significant technological breakthrough. This innovation offers considerable potential for expanding the application of mass cytometry for the detection of specific DNA sequences.},
}

@article {pmid40697935,
year = {2025},
author = {Simoroz, EV and Vasilevska, J and Arakelyan, NA and Manakhov, AD and Rogaev, EI},
title = {Unconventional animal models to study the role of telomeres in aging and longevity.},
journal = {Vavilovskii zhurnal genetiki i selektsii},
volume = {29},
number = {4},
pages = {496-507},
doi = {10.18699/vjgb-25-53},
pmid = {40697935},
issn = {2500-0462},
abstract = {The progressive shortening of telomeres is significantly implicated in various cellular processes related to aging, including the limitation of cellular proliferative lifespan through the activation of DNA damage response pathways, ultimately leading to replicative senescence. Telomere shortening is considered an indicator of biological age rather than chronological age. The restoration of telomere length is mediated by the enzyme telomerase; however, it is crucial to maintain a balance in this process, as excessive telomerase activity and overly elongated chromosomes may increase the susceptibility of individuals to cancer. It has been proposed that variations in telomere length among individuals of the same chronological age may be associated with differences in potential lifespan. However, recent studies suggest that telomere length may serve only as a rough estimate of the aging process and is likely not a clinically relevant biomarker for age-related diseases or mortality risk. Furthermore, variations in telomere length are not solely determined by chronological age; rather, they are modulated by a multitude of factors, including genetic predispositions, environmental conditions, and heightened metabolic activities such as reproduction and body weight, which may lead to increased telomere attrition in certain species. It has been argued that traditional animal models, such as the mouse (Mus musculus) and the rat (Rattus norvegicus domestica), are suboptimal for investigating the relationship between telomere length and aging, as their lifespans and telomere lengths do not adequately reflect those of humans. Consequently, it is recommended to use long-lived species as they would provide a more appropriate framework for such research initiatives. This review aims to examine the correlation between telomere length and longevity in various non-traditional long-lived animal models, evaluating their suitability for investigating the molecular mechanisms underlying telomere attrition in the context of aging. Nevertheless, the question of whether telomere length is a causative factor or a consequence of longevity remains an area that necessitates further investigation.},
}

@article {pmid40696438,
year = {2025},
author = {Wang, C and Chen, W and Li, R and Yang, Y and Wu, J and Tian, Y and He, Z and Lin, S and Wang, X and Zhu, J and Ma, W and Songyang, Z and Huang, Y},
title = {Disruption of ZC3H15 compromises telomere length maintenance by entrapping telomerase within cajal bodies.},
journal = {Cell & bioscience},
volume = {15},
number = {1},
pages = {107},
pmid = {40696438},
issn = {2045-3701},
support = {82271598//National Natural Science Foundation of China/ ; 82071587//National Natural Science Foundation of China/ ; 81871109//National Natural Science Foundation of China/ ; 31930058//National Natural Science Foundation of China/ ; 32330023//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Telomere homeostasis is pivotal in various biological processes including ontogeny, reproduction, physiological aging, and the onset of numerous diseases such as tumors. In human stem cells and approximately 85% of tumor cells, telomerase formed by TERT and TERC RNA complex is responsible for elongating telomeres. However, the intricate and precise regulatory mechanisms governing telomerase remain largely elusive.

METHODS AND RESULTS: We developed a genome-wide trimolecular fluorescence complementation (TriFC) screen to identify TERC RNA-interacting proteins and found ZC3H15 (Zinc finger CCCH domain-containing protein 15) to interact with telomerase. ZC3H15 interacts with TERT via its N-terminal domain in an RNA-dependent manner. The proximity labeling technique PhastID revealed that ZC3H15 associates with proteins involved in regulation of ribonucleoprotein (RNP) complex biogenesis, snRNP assembly and RNA localization. Deletion of ZC3H15 upregulated telomerase activity but interestingly resulted in shortened telomeres and induced senescence in HTC75 cells, suggesting an unknown mechanism in regulating telomere length. Notably, we found ZC3H15 to associate with GEMs nuclear bodies, and its deletion led to the spatiotemporal fusion of GEMs and Cajal bodies, resulting in the sequestration of telomerase within Cajal bodies and a reduction in telomerase recruitment to telomeres during the S phase. Consistent with these findings, ZC3H15 ablation accumulated TERC precursor RNA.

CONCLUSIONS: These observations provide valuable insights into the molecular mechanisms by which ZC3H15 regulates telomerase dynamics and cellular senescence. ZC3H15 may represent a new target for cancer treatment and anti-aging therapies.},
}

@article {pmid40695908,
year = {2025},
author = {Cao, H and Chu, X},
title = {Identification of telomere maintenance related biomarkers and regulatory mechanisms in chronic obstructive pulmonary disease by machine learning algorithm.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {26614},
pmid = {40695908},
issn = {2045-2322},
support = {Grant No. SRGS(24)060//Rugao City Mandatory Science and Technology Research Program/ ; },
mesh = {*Pulmonary Disease, Chronic Obstructive/genetics/metabolism/diagnosis ; Humans ; *Biomarkers/metabolism ; *Machine Learning ; Male ; Checkpoint Kinase 1/genetics/metabolism ; Molecular Docking Simulation ; *Telomere/metabolism/genetics ; Female ; Middle Aged ; Aged ; *Telomere Homeostasis ; Rad51 Recombinase/genetics/metabolism ; Rad52 DNA Repair and Recombination Protein/genetics/metabolism ; Algorithms ; },
abstract = {Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease that accelerates the aging process of the lung. Despite advancements in managing symptoms and preventing acute exacerbations, significant gaps remain in our understanding of the complex mechanisms that drive disease progression and contribute to mortality in COPD. In our work, we have successfully identified a set of five robust biomarkers (including RMI1, RAD51, RAD52, SNRNP70 and CHEK1). These biomarkers effectively distinguish COPD samples from normal samples, with area under the curve (AUC) value greater than 0.65 in the training set and greater than 0.80 in the validation set. Gene set enrichment analysis (GSEA) analysis showed that the main enrichment pathways were Non-alcoholic fatty liver disease, Spliceosome, Oxidative phosphorylation, etc. We also found these five genes had high accuracy in the diagnosis of COPD in both the training and verification sets. Molecular docking showed that the TOP5 small drug molecules acting with CHEK1 were U-0126, KN-62, BX-912, LY-294,002 and AZD-7762. The results of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) showed that there were significant differences in the expression of SNRNP70 and RAD52 between COPD and control samples (p < 0.05).},
}

*Pulmonary Disease, Chronic Obstructive/genetics/metabolism/diagnosis
Humans
*Biomarkers/metabolism
*Machine Learning
Male
Checkpoint Kinase 1/genetics/metabolism
Molecular Docking Simulation
*Telomere/metabolism/genetics
Female
Middle Aged
Aged
*Telomere Homeostasis
Rad51 Recombinase/genetics/metabolism
Rad52 DNA Repair and Recombination Protein/genetics/metabolism
Algorithms

@article {pmid40689372,
year = {2025},
author = {Farahzadi, R and Valipour, B and Fathi, E and Abolhasani, S},
title = {The role of telomeres in leukemic stem cells function.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {351-357},
pmid = {40689372},
issn = {2352-3204},
abstract = {The length of a telomere provides insight into the replication history of a cell. Notwithstanding the fact that the telomerase enzyme is produced by stem and progenitor cells, a considerable proportion of the documented telomere degradation takes place at these levels. Sequential transplantation remains a challenge for hematopoietic stem cells (HSCs) transfected with telomerase, despite their ability to maintain telomere length. To optimize stem cell proliferation, additional parameters must be considered [1]. In contrast, unregulated telomere depletion induced by HSCs appears to play a significant role in the pathogenesis of bone marrow failure, as demonstrated by dyskeratosis congenita. It implies that telomerase dysfunction serves as a prevalent ultimate pathogenic mechanism in this heterogeneous hereditary disorder. Although this condition is not well defined, acquired marrow failure syndromes have been linked to mutations in critical telomerase components. In light of the discovery of leukemic stem cells (LSCs) and the desire to develop anti-leukemia treatments for this population, a comprehensive understanding of the telomerase biology within this cell compartment is required. Further research must employ LSC-rich primary samples that have been selected. A more thorough understanding of the correlation between telomere length and telomerase regulation in this specific population may facilitate the creation of innovative approaches or small molecule inhibitors that specifically target the telomerase enzyme complex.},
}

@article {pmid40687635,
year = {2025},
author = {Comasco, E},
title = {Contextualizing Telomere Biology Through Biopsychological Plasticity: Insights From the Differential Susceptibility Hypothesis.},
journal = {Biological psychiatry global open science},
volume = {5},
number = {5},
pages = {100548},
pmid = {40687635},
issn = {2667-1743},
}

@article {pmid40674379,
year = {2025},
author = {Huang, SH and Balouchi, M and Kobryn, K},
title = {Conversion of a telomere resolvase into a Cre-like site-specific recombinase.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0328478},
pmid = {40674379},
issn = {1932-6203},
mesh = {*Telomere/metabolism/genetics ; *Bacterial Proteins/metabolism/genetics/chemistry ; *Integrases/metabolism/genetics ; Recombination, Genetic ; *Recombinases/metabolism/genetics ; Catalytic Domain ; Borrelia burgdorferi/enzymology/genetics ; *DNA Nucleotidyltransferases/metabolism/genetics ; Agrobacterium tumefaciens/enzymology/genetics ; *Endodeoxyribonucleases/metabolism/genetics ; },
abstract = {Hairpin telomere resolvases are a unique family of enzymes involved in producing the hairpin (hp) telomeres of bacterial organisms and phages that possess linear DNA's terminated by hp telomeres. The hp telomeres help to overcome the end-replication problem faced by linear DNAs and are generated from replicated intermediates of the linear DNAs. The telomere resolvases employ a reaction mechanism and catalytic domain related to that of the type IB topoisomerases and tyrosine recombinases. ResT, the telomere resolvase from Borrelia burgdorferi, under certain reaction conditions, has been shown to promote site-specific recombination between replicated telomere junctions (rTels) to produce a Holliday junction intermediate in a reaction strikingly similar to that promoted by tyrosine recombinases. TelA, the telomere resolvase of Agrobacterium tumefaciens, has been shown to be autoinhibited in such a manner as to forbid recombination between rTels. Relief of such autoinhibition reveals a weak, cryptic recombination activity in TelA. In the present study we characterize a catalytic domain aspartic acid residue mutation (D398A) that produces an enzyme with compromised telomere resolution activity but a massively stimulated ability to promote recombination between replicated telomere junctions to produce both the Holliday junction intermediate and full recombinant products of site-specific recombination between rTels. We also report that combination of the D398A mutation with previously characterized hyperactivating mutations in TelA produced a complete conversion of a telomere resolvase into a site-specific recombinase. The possible utility of this conversion is explored.},
}

*Telomere/metabolism/genetics
*Bacterial Proteins/metabolism/genetics/chemistry
*Integrases/metabolism/genetics
Recombination, Genetic
*Recombinases/metabolism/genetics
Catalytic Domain
Borrelia burgdorferi/enzymology/genetics
*DNA Nucleotidyltransferases/metabolism/genetics
Agrobacterium tumefaciens/enzymology/genetics
*Endodeoxyribonucleases/metabolism/genetics