@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

@article {pmid40673234,
year = {2025},
author = {Lu, J and Wu, H and Wang, F and Li, J and Wang, Y and Zhao, Q and Wang, Y and Wang, X and Lei, X and Sun, R and Zhang, J and Xiong, A and Deyholos, MK and Zhang, J},
title = {Telomere to telomere flax (Linum usitatissimum L.) genome assembly unlocks insights beyond fatty acid metabolism pathways.},
journal = {Horticulture research},
volume = {12},
number = {8},
pages = {uhaf127},
pmid = {40673234},
issn = {2662-6810},
abstract = {One of China's most important resources is flax (Linum usitatissimum L.), an ancient crop with significant nutritional and therapeutic benefits. Despite its importance, existing flax reference genomes remain incomplete, with many unassembled sequences. Here, we report a gapless 482.51 Mb telomere-to-telomere (T2T) flax genome assembly, predicting 46 634 genes, of which 42 805 were functionally annotated. Repetitive sequences constitute 60.05% of the genome, and we identified 30 telomeres and 15 centromeres across the chromosomes. Whole-genome duplication (WGD) events were detected at approximately 11.5, 53.5, and 114 million years ago (MYA) based on synonymous substitution rates (Ks). The T2T assembly enabled the reconstruction of the fatty acid metabolic pathway, identifying 49 related genes, including six newly annotated ones. Furthermore, genomic colocalization was observed between fatty acid metabolism pathway-related genes and transposable elements, suggesting that functional differentiation of these genes in flax evolution may have occurred through transposon-mediated duplication events. Phylogenetic analysis of SAD and FAD gene families revealed that FAD genes segregate into FAD2 and FAD3/7/8 subfamilies. Gene structure and motif analyses demonstrated conserved exon-intron architectures and motif organization within each phylogenetic clade of SAD and FAD genes. Promoter region characterization identified numerous cis-acting elements responsive to phytohormones (MeJA and abscisic acid) and abiotic stresses (low temperature and anaerobic induction) in both SAD and FAD genes. Our knowledge of the evolution of the flax genome is improved by this excellent genome assembly, which also offers a strong basis for enhancing agricultural attributes and speeding up molecular breeding.},
}

@article {pmid40672045,
year = {2025},
author = {Gründlinger, M and Ellensohn, C and Drechsel, L and Schreiner, U and Pierson, S and Baldin, C and Zeilinger, S},
title = {Simply cut out - Combining CRISPR/Cas9 RNPs and transiently selected telomere vectors for marker free-gene deletion in Trichoderma atroviride.},
journal = {Frontiers in genome editing},
volume = {7},
number = {},
pages = {1623963},
pmid = {40672045},
issn = {2673-3439},
abstract = {Trichoderma atroviride is a well-known mycoparasitic fungus widely used for the biological control of fungal plant pathogens. However, genetic manipulation in this organism remains challenging due to the limited availability of versatile and efficient molecular tools. Here, we present a CRISPR/Cas9-based method for targeted gene manipulation using ribonucleoprotein (RNP) complexes combined with a transiently stable telomere vector. We successfully inactivated three genes-pks4 (spore pigment production), pyr4 (pyrimidine biosynthesis), and pex5 (peroxisomal matrix protein import receptor)-to demonstrate the system's utility. Although double-strand breaks induced by Cas9 can be repaired via homology-directed repair (HDR), using donor templates, the most effective gene inactivations in our case were achieved via non-homologous end joining (NHEJ), by co-transforming the transiently stable telomere vector carrying the hygromycin-resistance gene (hph), which was rapidly lost under non-selective conditions. This strategy enables marker-free genetic manipulation, supports vector recycling, and simplifies successive transformations. Overall, our method expands the genetic toolbox for T. atroviride, offering a fast and reliable approach for reverse genetics in this agriculturally important fungus.},
}

@article {pmid40671231,
year = {2025},
author = {Ma, Y and Fang, X and Li, P},
title = {Telomere Maintenance Characteristics Predict Prognosis and Therapeutic Response in Colorectal Cancer.},
journal = {Current topics in medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115680266397024250710105241},
pmid = {40671231},
issn = {1873-4294},
abstract = {INTRODUCTION: The link between telomere length and Colorectal Cancer (CRC) risk and survival has been established. This study aims to investigate Telomere Maintenance-related Genes (TMGs) for predicting immunotherapy response and prognosis in CRC patients.

METHODS: In this study, gene expression data and clinical information of CRC patients were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and TMG-related scores were calculated for the samples. Subsequently, Weighted Gene Co- Expression Analysis (WGCNA) was used to identify gene modules that were highly correlated with the TMG score and intersected with differentially expressed genes to screen for potential functionally relevant candidate genes. The key genes significantly associated with prognosis were further analyzed using Cox regression analysis, from which key genes were identified, and a risk score model was constructed. Finally, the survival prediction ability of the model was evaluated across multiple cohorts, and differences in immune cell infiltration characteristics and drug sensitivity were analyzed within different risk groups.

RESULTS: A higher TMG score was noticed in CRC, and the TMG score was negatively correlated with the StromalScore, ImmuneScore, and ESTIMATEScore. Gene modules significantly associated with the TMG score were identified using WGCNA. Two key genes, CDC25C and USP39, which were closely associated with prognosis, were screened through differential expression analysis, and a risk score model was constructed. The model showed good survival prediction in both TCGA and GSE17537 independent cohorts. The scores of activated CD4 T cells, Type 17 T helper cells, Type 2 T helper cells, and neutrophils in the high-risk patients were lower, while the score of macrophages was higher in high-risk patients. Additionally, a negative correlation was observed between the risk score and the IC50 values of most drugs, as well as the enriched pathways of patients at high risk, which included epithelial-mesenchymal transition, angiogenesis, and myogenesis.

DISCUSSION: This study unveiled a TMG-related signature that predicts prognosis and immunotherapy in CRC. Based on the 2 prognostically relevant genes CDC25C and USP39, a reliable risk score model was established for the prognostic prediction, and the correlation between the drug sensitivity and the risk score was also explored.

CONCLUSION: This study reveals the significant value of TMGs in CRC prognostic assessment and immunotherapy response prediction, providing a new molecular basis for the development of individualized treatment strategies.},
}

@article {pmid40670383,
year = {2025},
author = {Yuan, G and Gao, Y and Tang, L and Xu, J and Liu, A and Tian, B and Yu, A},
title = {A telomere-to-telomere reference genome assembly of the red silk cotton tree (Bombax ceiba).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1250},
pmid = {40670383},
issn = {2052-4463},
support = {32261143461//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32360475//National Natural Science Foundation of China (National Science Foundation of China)/ ; 32260308//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
mesh = {*Genome, Plant ; *Telomere ; *Malvaceae/genetics ; },
abstract = {Bombax ceiba, an important ornamental tree and potential fiber resource in the textile industry, is widely distributed in tropical and subtropical regions. In this study, we assembled a nearly gap-free telomere-to-telomere (T2T) genome of B. ceiba using Illumina, PacBio High-fidelity (HiFi), ONT ultra-long, and Hi-C sequencing technologies. The genome spanned approximately 807.89 Mb, with a scaffold N50 of 16.58 Mb, and 754.68 Mb (93.41%) of genomic sequences were anchored onto 48 pseudo-chromosomes. Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis revealed a completeness of 99.40%, identifying 1,378 single-copy and 213 duplicated genes out of 1,614. The genome contained 67.72% (547.11 Mb) repeat regions, with 39,708 predicted protein-coding genes. Collectively, our study provides valuable genomic data for investigating the evolutionary history of the Malvaceae family.},
}

*Genome, Plant
*Telomere
*Malvaceae/genetics

@article {pmid40670029,
year = {2025},
author = {Calleri, A and Simonetto, DA},
title = {Telomere Disorders and the Liver.},
journal = {Clinics in liver disease},
volume = {29},
number = {3},
pages = {385-405},
doi = {10.1016/j.cld.2025.03.001},
pmid = {40670029},
issn = {1557-8224},
mesh = {Humans ; *Telomere/genetics ; *Liver Diseases/genetics/therapy ; *Telomere Shortening ; Hypertension, Portal/genetics ; },
abstract = {Telomeres are repetitive sequences at the ends of chromosomes that contribute to genome stability and prevent replicative senescence. Telomere biology disorders (TBDs) encompass a spectrum of genetic conditions characterized by accelerated telomere shortening, which affects different organs, including the liver. TBD-related hepatic manifestations are often unrecognized and can range from asymptomatic liver test abnormalities to steatohepatitis, hepatopulmonary syndrome, or cirrhotic and noncirrhotic portal hypertension requiring liver transplantation. This review summarizes the current literature and aims to describe liver involvement in TBDs, highlighting diagnostic gaps and therapeutic challenges.},
}

Humans
*Telomere/genetics
*Liver Diseases/genetics/therapy
*Telomere Shortening
Hypertension, Portal/genetics

@article {pmid40669867,
year = {2025},
author = {},
title = {Retraction and replacement of: Telomere-to-telomere genome and resequencing of 254 individuals reveal evolution, genomic footprints in Asian icefish, Protosalanx chinensis.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf066},
pmid = {40669867},
issn = {2047-217X},
}

@article {pmid40669866,
year = {2025},
author = {Zhou, Y and Wang, C and Wang, B and Xu, D and Zhang, X and Ge, Y and Jiang, S and Tang, F and Chen, C and Li, X and Jian, J and You, Y},
title = {Telomere-to-telomere genome and resequencing of 231 individuals reveal evolution, genomic footprints in Asian icefish, Protosalanx chinensis.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf067},
pmid = {40669866},
issn = {2047-217X},
support = {2023YFD2400900//National Key R&D Program of China/ ; CARS-46//Modern Agricultural Technology System/ ; },
mesh = {*Telomere/genetics ; Animals ; *Evolution, Molecular ; *Genome ; Genetic Variation ; Genomics/methods ; Genetics, Population ; },
abstract = {The Asian icefish, Protosalanx chinensis, has undergone extensive colonization in various waters across China for decades due to its ecological and physiological significance as well as its economic importance in the fishery resource. Here, we decoded a telomereto-telomere (T2T) genome for P. chinensis combining PacBio HiFi long reads and ultra-long ONT (nanopore) reads and Hi-C data. The telomere was identified in both ends of the contig/chromosome. The expanded gene associated with circadian entrainment suggests that P. chinensis may exhibit a high sensitivity to photoperiod. The contracted genes' immune-related families and DNA repair associated with positive selection in P. chinensis suggested the selection pressure during adaptive evolution. The population genetic analysis reported the genetic diversity and genomic footprints in 231 individuals from 7 different locations. The introduced highest alkalinity population (HRCL) exhibited higher values of inbreeding coefficients and clustered different from other groups suggested local environmental adaptation. Thus, the T2T genome and genetic variation can be valuable resources for genomic footprints in P. chinensis, shedding light on its evolution, comparative genomics, and the genetic differences between natural and introduced populations.},
}

*Telomere/genetics
Animals
*Evolution, Molecular
*Genome
Genetic Variation
Genomics/methods
Genetics, Population

@article {pmid40669068,
year = {2025},
author = {Cheng, X and Liu, L and Guo, H and Liu, L and Wang, Y and Zhang, J and Gao, J and Yan, Y and An, J and Tan, Y and He, M},
title = {Association of Serum Per- and Polyfluoroalkyl Substances Exposure with Leukocyte Telomere Length in Chinese Middle-Aged and Older Adults: Role of Genetic Susceptibility and Healthy Diet.},
journal = {Environmental science & technology},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.est.5c05958},
pmid = {40669068},
issn = {1520-5851},
abstract = {The association between per- and polyfluoroalkyl substances (PFASs) and leukocyte telomere length (LTL) remains unclear, especially with regard to the roles of genetic and dietary factors. The study population was a subsample of the baseline survey from a nested case-control study within the Dongfeng-Tongji cohort study, with a total of 1489 middle-aged and older adults included. We measured serum levels of 10 PFASs, as well as peripheral blood LTL, and constructed a polygenic score (PGS) and a healthy diet score. Associations between PFASs and LTL were analyzed by using general linear regression. Both multiplicative interaction terms and stratified analyses were used for the assessment of the modification effects. Serum perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUDA) were negatively associated with LTL. A doubling of PFDA or PFUDA levels led to a significant decrease in LTL [percent change (95% CI): -1.55 (-2.82, -0.27); -1.61 (-3.01, -0.19), respectively]. Significant associations of PFAS exposure and PGS with LTL were observed in those with a low healthy diet score. In the low-score group, participants with high PFAS exposure (especially, PFOA, PFNA, PFDA, and PFUDA) and high PGS had the shortest LTL [percent change (95% CI): -16.04 (-22.94, -8.53) for high PFNA and high PGS and -11.96 (-19.10, -4.18) for high PFUDA and high PGS]. This study revealed that PFAS exposure was associated with LTL shortening, and those with low healthy diet scores are vulnerable to the joint effects of PFAS exposure and genetic susceptibility, offering insights for regulatory and public health actions.},
}

@article {pmid40668659,
year = {2025},
author = {Gomes, WR and Hama, S and Napolitani, G and Tan, A and Catto, LFB and Donaires, FS and Santana, BA and Carvalho, VS and Martinez, EZ and Condino-Neto, A and Karimi, MM and Mufti, GJ and Calado, RT},
title = {Immune cells display an abnormal maturation and a pro-inflammatory profile in telomere biology disorders.},
journal = {Blood advances},
volume = {},
number = {},
pages = {},
doi = {10.1182/bloodadvances.2025015976},
pmid = {40668659},
issn = {2473-9537},
abstract = {Pathogenic germline variants causing excessive telomere shortening may result in bone marrow failure, hematopoietic malignancy, and extramedullary complications, such as pulmonary fibrosis, liver cirrhosis, and solid tumors. Patients with short telomeres also develop immunodeficiency with low CD4+ T cells and impaired general immunosurveillance, particularly against solid neoplasms. We investigated a broad spectrum of lymphocyte subsets and myeloid immune cells from human patients with telomere biology disorders (TBDs) and matched healthy volunteers to understand further how the immune system is affected by telomere dysfunction. We employed mass cytometry (CyTOF) for deep-immunophenotyping peripheral blood mononuclear cells (PBMCs), followed by high-dimensional data analysis. Cytokines, chemokines, and growth factors were assessed in serum. Our results showed profound immune alterations in TBD beyond those observed in aging, with low naïve lymphocytes and thymic hypofunction. We further observed that T helper subsets were markedly skewed, with an inverted TH2/TH1 ratio and low TH17 and TH17.1 levels. T cell activation and exhaustion markers were upregulated, whereas circulating mucosal-associated invariant T (MAIT) cells were significantly decreased and overactivated. Several serum cytokine levels were positively correlated with telomere length and blood counts, suggesting an association with marrow function. In aggregate, these findings suggest a pro-inflammatory profile in TBDs. Our data provide new details on how TBD affects immune cells, particularly lymphocytes, which may contribute to the clinical phenotypes.},
}

@article {pmid40666524,
year = {2025},
author = {Zhen, S and Huang, L and Zhu, Q and Chen, R and Wang, J and Zha, X},
title = {Identification and validation of genes related to stem cells and telomere maintenance mechanisms as biomarkers for breast cancer.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1618193},
pmid = {40666524},
issn = {1664-3224},
mesh = {Humans ; *Breast Neoplasms/genetics/pathology/metabolism ; Female ; *Biomarkers, Tumor/genetics ; Gene Expression Regulation, Neoplastic ; Gene Expression Profiling ; *Neoplastic Stem Cells/metabolism/pathology ; *Telomere Homeostasis/genetics ; *Telomere/genetics ; Protein Interaction Maps ; Transcriptome ; Single-Cell Analysis ; Middle Aged ; },
abstract = {BACKGROUND: Stem cell-related genes (SCRGs) and telomere maintenance mechanism-related genes (TMMRGs) are pivotal in breast cancer (BC) pathogenesis by facilitating tumor cell proliferation and self-renewal. This study employed integrated transcriptomic and single-cell RNA sequencing (scRNA-seq) analyses to investigate SCRGs and TMMRGs as potential biomarkers for BC and to elucidate their underlying cellular mechanisms.

METHODS: Total RNA was extracted from eight BC tumor samples and eight matched adjacent non-tumorous tissues. Differential expression profiling, protein-protein interaction (PPI) network construction, and Molecular Complex Detection (MCODE) were conducted. Biomarker candidates were identified using the least absolute shrinkage and selection operator (LASSO) algorithm, followed by pathway enrichment and immunological analyses. Publicly available scRNA-seq datasets were utilized to delineate BC cell types, with emphasis on cellular subsets exhibiting differential biomarker expression. Heterogeneity, communication, and pseudo-temporal analyses of key cells were examined. Biomarker expression was further validated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

RESULTS: JUN, NFKB1, and SP1 were significantly downregulated in BC, potentially modulating disease progression through mechanisms involving extracellular matrix (ECM) remodeling, intracellular signaling, oxidative stress response, and translational regulation. Activated B cells and natural killer (NK) cells demonstrated elevated infiltration levels, accompanied by increased expression of immune checkpoint molecules CD200, CD274, TIGIT, TNFRSF25, and TNFSF15. Nine distinct cellular lineages were annotated, among which mesenchymal cells exhibited pronounced biomarker expression differences and enhanced differentiation potential, designating them as key cellular mediators. Interactions between mesenchymal subpopulations (MSC1, MSC2, MSC3) and other cell types were markedly reduced in BC, despite an overall expansion in mesenchymal cell numbers during disease progression. MSC1 emerged as the predominant subtype. RT-qPCR analyses corroborated the downregulation of JUN, NFKB1, and SP1 in BC tissues.

CONCLUSION: JUN, NFKB1, and SP1 were identified as potential biomarkers for BC. These findings highlight the critical role of mesenchymal cells in tumor biology and suggest potential therapeutic targets.},
}

Humans
*Breast Neoplasms/genetics/pathology/metabolism
Female
*Biomarkers, Tumor/genetics
Gene Expression Regulation, Neoplastic
Gene Expression Profiling
*Neoplastic Stem Cells/metabolism/pathology
*Telomere Homeostasis/genetics
*Telomere/genetics
Protein Interaction Maps
Transcriptome
Single-Cell Analysis
Middle Aged

@article {pmid40665468,
year = {2025},
author = {},
title = {Correction to: The telomere-to-telomere gapless genome of grass carp provides insights for genetic improvement.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf088},
pmid = {40665468},
issn = {2047-217X},
}

@article {pmid40665466,
year = {2025},
author = {Jiang, M and Zhao, C and Ma, F and Yin, D and Wang, C and Jian, J and Liu, K},
title = {The telomere-to-telomere gap-free reference genome and taxonomic reassessment of Siniperca roulei.},
journal = {GigaScience},
volume = {14},
number = {},
pages = {},
doi = {10.1093/gigascience/giaf068},
pmid = {40665466},
issn = {2047-217X},
support = {2023TD11//Chinese Academy of Fishery Sciences, Central Public-Interest Scientific Institution Basal Research Fund, CAFS/ ; JSZC-202209051607//Chinese Academy of Fishery Sciences, Monitoring of Aquatic Living Resources in Jiangsu Section in the Mainstream of the Yangtze River/ ; },
mesh = {*Telomere/genetics ; *Genome, Plant ; Phylogeny ; Genomics/methods ; Molecular Sequence Annotation ; China ; },
abstract = {Siniperca roulei is primarily distributed in the eastern waters of China, with its population being both scarce and vulnerable. Research on this species remains limited, with few studies conducted on its biology and genetics, which hampers efforts to conserve its germplasm resources. To support breeding and conservation efforts, we generated a gap-free genome assembly using a combination of DNBSeq short reads, PacBio HiFi long reads, Nanopore ultra-long reads, and Hi-C data. The nearly telomere-to-telomere (T2T) genome of S. roulei spans 717.34 Mb, with a contig N50 of 30.25 Mb, and each chromosome is represented by a single contig. A total of 26,596 genes were predicted, with 87.97% functionally annotated. These high-precision genomic data provide valuable insights into the germplasm resources of S. roulei, offering crucial information for clarifying the taxonomic status and evolutionary history of sinipercids. These findings are significant for the conservation and sustainable use of its germplasm resources.},
}

*Telomere/genetics
*Genome, Plant
Phylogeny
Genomics/methods
Molecular Sequence Annotation
China

@article {pmid40665355,
year = {2025},
author = {Ding, K and Liu, L and Yong, W and Sun, B and Zhang, W},
title = {Bioinformatics analysis and experimental studies reveal KPNA2 as a novel biomarker of hepatocellular carcinoma progression and telomere maintenance.},
journal = {European journal of medical research},
volume = {30},
number = {1},
pages = {628},
pmid = {40665355},
issn = {2047-783X},
support = {82371850//National Natural Science Foundation of China/ ; AHWJ2024BAc20031//Health Research Program of Anhui/ ; 2024AH020008//Distinguished Young Scholar of Anhui Provincial Department of Education/ ; },
mesh = {Humans ; *Carcinoma, Hepatocellular/genetics/pathology/metabolism ; *Liver Neoplasms/genetics/pathology/metabolism ; *alpha Karyopherins/genetics/metabolism ; *Biomarkers, Tumor/genetics/metabolism ; Computational Biology/methods ; Disease Progression ; Prognosis ; Gene Expression Regulation, Neoplastic ; *Telomere/genetics ; Cell Proliferation/genetics ; *Telomere Homeostasis/genetics ; Protein Interaction Maps ; },
abstract = {BACKGROUND: Telomere maintenance mechanisms (TMMs) play a distinct role in the initiation and progression of hepatocellular carcinoma (HCC). However, the prognostic relevance of telomere maintenance (TM)-related genes in HCC remains largely unclear.

METHODS: We integrated expression profiles of TM-related genes and corresponding clinicopathological data from public databases. Univariate analyses were performed to identify prognostic genes, and Cytoscape software was used to validate hub genes within the TM-related network. A novel prognostic signature was then constructed using the LASSO Cox regression algorithm. Finally, in vitro experiments were conducted to explore the functional roles of the key hub gene KPNA2 in telomere maintenance, tumor growth, and metastasis in HCC.

RESULTS: In this study, we identified 224 differentially expressed TM-related genes for the first time. Functional enrichment and pathway analyses revealed that these genes were highly involved in telomere-associated pathways, including cell proliferation and cellular senescence. Protein-protein interaction (PPI) analysis identified eight hub TM-related genes (RNASEH2A, KPNA2, AURKB, FOXM1, MKI67, RAD54L, PLK1, and KIF4A), all of which were positively correlated with telomere maintenance. Furthermore, a novel TM-related prognostic signature comprising seven genes (KPNA2, CACNA1B, IRAK1, CDCA8, RGMA, ETS2, and GNE) was developed using the LASSO Cox model. Notably, KPNA2 was identified as both a TM-related hub gene and a component of the prognostic signature. KPNA2 was found to be significantly upregulated in HCC and associated with poor clinical outcomes. Functional assays revealed that KPNA2 knockdown suppressed telomerase activity, inhibited tumor cell proliferation and metastasis, whereas its overexpression produced the opposite effects. Telomerase inhibition partially alleviated the inhibitory effect of KPNA2 overexpression on cell proliferation and migration.

CONCLUSIONS: This study identified eight TM-related hub genes with prognostic significance in HCC and established a novel TM-related gene signature. Furthermore, we validated KPNA2 as a key regulator of telomere maintenance and tumor progression in HCC, suggesting it as a potential therapeutic target for improving clinical management of HCC.},
}

Humans
*Carcinoma, Hepatocellular/genetics/pathology/metabolism
*Liver Neoplasms/genetics/pathology/metabolism
*alpha Karyopherins/genetics/metabolism
*Biomarkers, Tumor/genetics/metabolism
Computational Biology/methods
Disease Progression
Prognosis
Gene Expression Regulation, Neoplastic
*Telomere/genetics
Cell Proliferation/genetics
*Telomere Homeostasis/genetics
Protein Interaction Maps

@article {pmid40659358,
year = {2025},
author = {Sidarava, V and Mearns, S and Lydall, D},
title = {Long telomere inheritance through budding yeast sexual cycles.},
journal = {Genetics},
volume = {},
number = {},
pages = {},
doi = {10.1093/genetics/iyaf129},
pmid = {40659358},
issn = {1943-2631},
abstract = {The ends of linear eukaryotic chromosomes are protected from being recognized as DNA double-strand breaks by telomeres, containing repetitive DNA sequences which bind specific proteins. In humans, mutations in telomere regulatory genes lead to short or long telomere syndromes. These syndromes often show genetic anticipation, where disease has earlier onset and a more severe manifestation in each new generation. Later generations inherit not only the mutation affecting telomere length, but also abnormal length telomeres. Many aspects of telomere length homeostasis are conserved between mammals and yeast. Here we explored telomere length inheritance patterns through the sexual cycle in yeast. Analysis of single telomeres, rather than bulk telomeres, shows that if haploid yeast with short telomeres mate with wild-type yeast creating diploids, short telomere lengths rapidly normalize (within 30 cell divisions). However, long telomeres inherited from one parent can persist for more than 200 mitotic cell divisions. Long telomere can also be transmitted through more than one round of meiosis, independently of mutations that cause long telomeres. These patterns, along with haploinsufficiency effects, show that even in yeast there is a complex relationship between telomere length, telomere length inheritance, and mutations that affect telomere length. Our findings may have implications for families affected by telomere syndromes.},
}

@article {pmid40654789,
year = {2025},
author = {Zhang, H and Audry, J and Runge, KW},
title = {A Chromosome End Without Terminal Telomere Repeats is Stable for Multiple Cell Divisions.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.05.01.651670},
pmid = {40654789},
issn = {2692-8205},
abstract = {We have formed new short telomeres in Schizosaccharomyces pombe using an inducible nuclease that cuts near telomere repeats in cells that lack, cannot recruit or cannot fully activate telomerase. Sequencing these new telomeres showed that cells can divide at least 4 times with ∼30 bp of non-telomeric sequence at the chromosome end in cells lacking telomerase, which contrasts with current models for the roles of terminal single-stranded telomere repeats and the telomere proteins in telomere protection and replication. Cells that cannot recruit or activate telomerase had similar results, with additional rearrangements or telomere repeat addition, respectively.},
}

@article {pmid40654587,
year = {2025},
author = {Minelli, A and Meloni, A and Bortolomasi, M and Pisanu, C and Zampieri, E and Congiu, D and Lana, B and Manchia, M and Meattini, M and Paribello, P and , and Baune, BT and Gennarelli, M and Squassina, A},
title = {Telomere length and mitochondrial DNA copy number in association with trauma-focused psychotherapy efficacy.},
journal = {Neuroscience applied..},
volume = {4},
number = {},
pages = {104095},
pmid = {40654587},
issn = {2772-4085},
abstract = {Early life adversities (ELA) have been linked to a greater risk for major depressive disorder (MDD) and treatment-resistant depression (TRD). The molecular mechanisms underlying the link between ELA and MDD and/or TRD are yet unknown. It has been suggested that ELA induces an allostatic burden, which in turn promotes oxidative stress and an inflammatory response that are further intensified by the influence of maladaptive coping behaviour. In this study we explored the role of two markers of cellular aging and oxidative stress (leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn)) in TRD and in response to trauma-focused psychotherapies. The study comprised 30 TRD patients receiving trauma-focused psychotherapies and 65 healthy controls. LTL and mtDNAcn were measured at baseline and four weeks after the end of the psychotherapy sessions. Response was defined based on reduction in the Montgomery-Åsberg Depression Rating Scale (MADRS). In the case control analysis, the logistic regression model showed that mtDNAcn but not LTL was a significant predictor of diagnosis (chi-square 92.108, p = 7.72e-20; contribution of mtDNAcn, B = -9-297, p = 0.00009). In the TRD sample, LTL and mtDNAcn were inversely correlated with MADRS score at baseline (LTL, Pearson's r = -0.478, p = 0.008; mtDNAcn, Pearson's r = -0.656, p = 0.00008), but there was no difference in either LTL or mtDNAcn between responders and non-responders. In conclusion, our findings support an involvement of cellular aging in TRD, and suggest that LTL and mtDNAcn are not predictors or mediators of response to trauma-focused psychotherapies.},
}

@article {pmid40646001,
year = {2025},
author = {Zhang, K and Chen, J and Duan, B and You, C and Zhou, W and Zhao, Y and Yang, S and Wu, J and Shi, Q},
title = {A telomere-to-telomere gap-free genome assembly of the endangered humphead wrasse (Cheilinus undulatus).},
journal = {Scientific data},
volume = {12},
number = {1},
pages = {1194},
pmid = {40646001},
issn = {2052-4463},
mesh = {Animals ; Endangered Species ; *Genome ; *Telomere ; *Perciformes/genetics ; Repetitive Sequences, Nucleic Acid ; },
abstract = {Humphead wrasse, Cheilinus undulatus, is an endangered fish species with high economic and ecological value as well as natural sex change from female to male, while sexual selection occurs in breeding aggregations. In our present study, we constructed the first gap-free telomere-to-telomere (T2T) genome assembly for humphead wrasse, by integration of PacBio HiFi, ONT Ultra-long and Hi-C sequencing techniques. With 99% of the entire sequences anchored into 24 chromosomes, this haplotypic genome assembly spans approximately 1.25 Gb and presents a complete set of 48 telomeres and 24 centromeres. In terms of correctness (quality value QV: 53.447) and completeness (BUSCO score: 99.3%), this chromosome-scale assembly is indeed of high quality. We predicted 658.03 Mb of repetitive sequences and annotated 26,609 protein-coding genes in the assembled genome. This high-quality T2T genome assembly not only facilitates the genetic conservation of humphead wrasse, but also offers fundamental genomic data for supporting in-depth investigations on functional genomics, genetic diversity, and selective breeding for this economically important teleost.},
}

Animals
Endangered Species
*Genome
*Telomere
*Perciformes/genetics
Repetitive Sequences, Nucleic Acid

@article {pmid40645989,
year = {2025},
author = {Vaurs, M and Claude, E and Zanella, E and Rodrigues, J and Nassour, J and Karlseder, J and Azzalin, CM and Doksani, Y and Decottignies, A},
title = {TRF1 relies on fork reversal to prevent fragility at human telomeres.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6439},
pmid = {40645989},
issn = {2041-1723},
support = {AIRC IG 28954//Associazione Angela Serra per la Ricerca sul Cancro (Associazione Angela Serra)/ ; AIRC IG 28954//Associazione Angela Serra per la Ricerca sul Cancro (Associazione Angela Serra)/ ; WWCR 24-0166/AICR_/Worldwide Cancer Research/United Kingdom ; WWCR 24-0166/AICR_/Worldwide Cancer Research/United Kingdom ; K99-R00CA252447//U.S. Department of Health & Human Services | NIH | NCI | Division of Cancer Epidemiology and Genetics, National Cancer Institute (National Cancer Institute Division of Cancer Epidemiology and Genetics)/ ; AG0773424, CA234047, P30CA014195 and GM142173//U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)/ ; },
mesh = {Humans ; *Telomere/metabolism/genetics ; *Telomeric Repeat Binding Protein 1/metabolism/genetics ; *DNA Replication ; Telomerase/metabolism/genetics ; DNA Primase/metabolism ; },
abstract = {Telomeres pose challenges during replication, with converging forks unlikely to resolve issues. Depleting TRF1 results in fragile telomeres, yet its exact role in telomere replication remains unclear. In our cellular model, insufficient TRF1 density at long telomeres leads to telomere fragility that is alleviated by restoring telomeric TRF1 levels. Our findings indicate that TRF1 mitigates lagging strand telomere fragility through fork reversal in a process involving telomerase activity, rather than merely alleviating fork barriers. Additionally, TFIIH, a crucial partner of TRF1, aids in restarting replication on the leading strand after fork reversal. When fork reversal is compromised, PrimPol-mediated repriming rescues fragility at leading strand telomeres, revealing a new role for this enzyme in human telomere replication. Lastly, our findings indicate that the TRF1-mediated decrease in telomere fragility is dependent on RNA:DNA hybrids, likely facilitating fork restart.},
}

Humans
*Telomere/metabolism/genetics
*Telomeric Repeat Binding Protein 1/metabolism/genetics
*DNA Replication
Telomerase/metabolism/genetics
DNA Primase/metabolism

@article {pmid40645667,
year = {2025},
author = {Bloom, SI and Karlseder, J},
title = {Telomeres at the nexus of aging, tumor suppression, and inflammation: toward an understanding beyond senescence.},
journal = {Genes & development},
volume = {},
number = {},
pages = {},
doi = {10.1101/gad.353122.125},
pmid = {40645667},
issn = {1549-5477},
abstract = {Aging is the greatest risk factor for most diseases. We propose that aging manifests as disease as a function of tumor-suppressive capabilities. Adequate tumor suppression results in cell death or an accumulation of damaged cells leading to inflammation and tissue dysfunction that underlies diseases such as cardiovascular disease, neurodegenerative diseases, or type 2 diabetes. Conversely, inadequate tumor suppression leads to cancer. Telomeres are central to this process because they oppose hyperproliferation that is required for cancer initiation by enforcing two potent tumor suppressor mechanisms: senescence and crisis. Although senescent cells promote age-related diseases via inflammatory signaling, crisis cells have lost the p53 and RB pathways, have more unstable genomes, and harbor shorter telomeres, all of which could increase inflammation to a greater degree than is seen in senescence. This model emphasizes the intimate relationship between aging, telomeres, tumor suppression, and inflammation and suggests that crisis cells may represent an unexplored driver of inflammation in advanced age.},
}

@article {pmid40644351,
year = {2025},
author = {Holesova, Z and Budis, J and Kucharik, M and Gazdarica, J and Carska, D and Minarik, G and Hyblova, M and Szemes, T},
title = {Telomere length as a biomarker for fetal fraction prediction in non-invasive prenatal testing.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0327714},
pmid = {40644351},
issn = {1932-6203},
mesh = {Humans ; Female ; Pregnancy ; *Telomere/genetics ; Biomarkers/blood ; Cell-Free Nucleic Acids/blood/genetics ; *Fetus/metabolism ; *Prenatal Diagnosis/methods ; Adult ; *Noninvasive Prenatal Testing/methods ; *Telomere Homeostasis ; },
abstract = {Non-invasive prenatal testing (NIPT) has revolutionized prenatal diagnostics by providing a safer alternative to invasive techniques such as amniocentesis and chorionic villus sampling. NIPT detects chromosomal abnormalities through the analysis of cell-free fetal DNA (cffDNA) in maternal plasma. One of the critical factors influencing accuracy of NIPT is the fetal fraction (FF) - the proportion of fetal cell-free DNA relative to total cell-free DNA in maternal plasma. This study investigates the potential of using telomere length measurements as a novel biomarker for fetal fraction prediction in NIPT. Telomere-derived fragments, which differ between maternal and fetal DNA, may serve as a measure of FF due to the distinct telomere length. Specifically, deviations from the expected shorter telomere lengths of maternal DNA toward longer lengths could be more pronounced at higher FF levels. Various models incorporating telomere content and features selected by Ordinary Least Squares (OLS) were evaluated to enhance fetal fraction prediction. Our results showed that telomere content also works as an independent predictor (with Pearson correlation 0.23), yielding a small improvement in prediction precision when combined with traditional models.},
}

Humans
Female
Pregnancy
*Telomere/genetics
Biomarkers/blood
Cell-Free Nucleic Acids/blood/genetics
*Fetus/metabolism
*Prenatal Diagnosis/methods
Adult
*Noninvasive Prenatal Testing/methods
*Telomere Homeostasis

@article {pmid40642293,
year = {2025},
author = {Sun, L and Zhang, T and Luo, L and Yang, Y and Wang, C and Luo, J},
title = {Exercise delays aging: evidence from telomeres and telomerase -a systematic review and meta-analysis of randomized controlled trials.},
journal = {Frontiers in physiology},
volume = {16},
number = {},
pages = {1627292},
pmid = {40642293},
issn = {1664-042X},
abstract = {OBJECTIVE: To systematically evaluate the regulatory effects of exercise intervention on telomere length (TL) and telomerase activity (TA), and to provide evidence for formulating precise exercise prescriptions based on telomere protection.

METHODS: Databases including China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Web of Science, Cochrane Library, and Embase were searched to collect randomized controlled trials (RCTs) regarding the regulation of TL and TA by exercise intervention up to February 2025. The Cochrane risk assessment tool was used to evaluate the quality of the included literature. Meta-analysis, heterogeneity test, subgroup analysis, sensitivity analysis, univariate meta-regression analysis, and publication bias test were conducted using Review Manager 5.3 and Stata 18.0 software.

RESULTS: Exercise intervention significantly maintained TL (SMD = 0.59, 95% CI: 0.14-1.06, P = 0.01) and enhanced TA (SMD = 0.35, 95% CI: 0.20-0.51, P < 0.00001). A single study suggests high-intensity interval training (HIIT) may maintain TL (SMD = 0.66, P = 0.01), but this requires further validation due to limited evidence. Aerobic exercise (AE) consistently increased TA (SMD = 0.33, P = 0.0001), while resistance exercise (RE) showed non-significant trends (SMD = 0.16, P = 0.43). Subgroup analysis by sex showed a trend toward greater TL maintenance in females (SMD = 0.48, P = 0.06) compared to males (SMD = 0.38, P = 0.40). An exercise duration of ≥16 weeks was necessary for significant effects. High heterogeneity (I2 = 92% for TL) was partially explained by measurement methods, age, and baseline health.

CONCLUSION: Exercise maintains TL and enhances TA, potentially contributing to delayed aging. AE shows robust effects on TA, while HIIT and RE require further research due to limited studies. Future studies should standardize measurement methods and explore confounders like diet and genetics.

PROSPERO, identifier CRD420251006569.},
}

@article {pmid40640368,
year = {2025},
author = {Muñoz-Pardeza, J and López-Gil, JF and Huerta-Uribe, N and Hormazábal-Aguayo, I and Ojeda-Rodríguez, A and Del Moral, AM and Izquierdo, M and García-Hermoso, A},
title = {Telomere length in youth with type 1 diabetes and the role of physical fitness.},
journal = {Pediatric research},
volume = {},
number = {},
pages = {},
pmid = {40640368},
issn = {1530-0447},
}

@article {pmid40635494,
year = {2025},
author = {Joo, YB and Bang, SY and Hong, SJ and Lee, Y and Shin, D and Bae, SC and Lee, HS},
title = {Association of peripheral leukocyte telomere length with patients with rheumatoid arthritis with a focus on interstitial lung disease.},
journal = {The Korean journal of internal medicine},
volume = {40},
number = {4},
pages = {676-686},
doi = {10.3904/kjim.2024.148},
pmid = {40635494},
issn = {2005-6648},
support = {2021R1A6A1A03038899//National Research Foundation of Korea/ ; //Ministry of Education/ ; },
mesh = {Humans ; *Arthritis, Rheumatoid/genetics/complications/diagnosis/blood ; Male ; Female ; Middle Aged ; *Lung Diseases, Interstitial/genetics/blood/diagnosis/etiology ; Aged ; Case-Control Studies ; *Leukocytes ; *Telomere ; *Telomere Shortening ; Adult ; *Telomere Homeostasis ; },
abstract = {BACKGROUND/AIMS: This study investigated whether telomere length (TL) in rheumatoid arthritis (RA) patients is shorter than in controls, whether TL in RA patients with interstitial lung disease (RA-ILD) differs from that in those without ILD (RA-nonILD), and whether TL varies according to RA-ILD patterns.

METHODS: TL was measured in peripheral leukocytes using quantitative polymerase chain reaction. Results were compared between controls (n = 14), RA (n = 70), RA-ILD (n = 53), and RA-nonILD (n = 53), and between the subgroups with usual interstitial pneumonia (UIP; n = 32) and nonspecific interstitial pneumonia (NSIP; n = 8), with age- and sex-matching in each comparison. The correlation between TL and honeycombing extent was determined.

RESULTS: RA patients had significantly shorter TL (8.3 ± 2.5 kb) than controls (9.5 ± 0.8 kb; p = 0.002). No significant TL difference was found between RA-ILD and RA-nonILD (8.2 ± 2.8 vs 7.7 ± 2.4 kb, p = 0.271). Among RA-ILD, age (p = 0.011), disease activity (p = 0.018), and UIP (p = 0.038) were significantly associated with shortened TL. TL in UIP was shorter than in NSIP (7.4 ± 1.9 vs. 10.0 ± 3.1 kb, p = 0.026). Honeycombing extent in UIP showed a negative correlation with TL but it was nonsignificant (Rho = -0.131, p = 0.387).

CONCLUSION: This study confirms that RA is associated with shorter TL than in healthy individuals and suggests variations in TL among RA-ILD subtypes, indicating that telomere involvement in pathogenesis may differ by subtype.},
}

Humans
*Arthritis, Rheumatoid/genetics/complications/diagnosis/blood
Male
Female
Middle Aged
*Lung Diseases, Interstitial/genetics/blood/diagnosis/etiology
Aged
Case-Control Studies
*Leukocytes
*Telomere
*Telomere Shortening
Adult
*Telomere Homeostasis

@article {pmid40632247,
year = {2025},
author = {Dahlqvist, C and Planté-Bordeneuve, T and Muca, T and de Leener, A and Ghaye, B and Coche, E and Decottignies, A and van Dievoet, MA and Froidure, A},
title = {Use of Telomere Length as a Biomarker in Idiopathic Pulmonary Fibrosis.},
journal = {Lung},
volume = {203},
number = {1},
pages = {78},
pmid = {40632247},
issn = {1432-1750},
mesh = {Humans ; Male ; *Idiopathic Pulmonary Fibrosis/genetics/physiopathology/diagnosis ; Female ; Aged ; Middle Aged ; Mutation ; *Telomere Shortening ; *Telomere/genetics ; Telomerase/genetics ; Vital Capacity ; Biomarkers ; *Lung/physiopathology ; Respiratory Function Tests ; Aged, 80 and over ; Belgium ; Disease Progression ; },
abstract = {BACKGROUND: Telomere shortening, a hallmark of cellular aging, is associated with poor outcomes in idiopathic pulmonary fibrosis (IPF). This study aimed to explore the relationships between telomere length (TL), pulmonary function tests, and telomere-related gene (TRG) mutations in a real-world IPF population.

METHODS: We included IPF patients from two Belgian academic hospitals, collecting demographic and clinical data. TL was measured using Flow-FISH and expressed as a percentile. Short TL was defined as below the 10th percentile (P10), and very short TL as below the 1st percentile (P1).

RESULTS: We analysed 143 patients (106 men, 74%), with a median age of 70 years. Thirty patients (21%) met the European Respiratory Society (ERS) criteria for familial pulmonary fibrosis (FPF). Short TL was found in 74 patients (50%), predominantly in men (p < 0.05). Patients with short TL experienced a greater decline in lung function over 24 months compared to those with normal TL (- 4% vs + 3% FVC, p < 0.05; - 7% vs - 3% DLCO, p < 0.05). Patients with very short TL were younger at diagnosis and tended to have a more pronounced FVC decline (- 5% vs - 1%, p = 0.06). TRG variants were identified in 16 individuals, occurring more frequently in those with short (14/27, 52%) or very short TL (10/20, 50%).

CONCLUSION: Short TL is common in both sporadic and familial IPF and serves as a predictive biomarker for accelerated lung function decline. Additionally, the presence of short TL is indicative of an underlying TRG mutation.},
}

Humans
Male
*Idiopathic Pulmonary Fibrosis/genetics/physiopathology/diagnosis
Female
Aged
Middle Aged
Mutation
*Telomere Shortening
*Telomere/genetics
Telomerase/genetics
Vital Capacity
Biomarkers
*Lung/physiopathology
Respiratory Function Tests
Aged, 80 and over
Belgium
Disease Progression

@article {pmid40629711,
year = {2025},
author = {Jin, H and Song, J and Gao, R and Sha, B and Wang, S and Luo, P and Yu, L and Xu, X and Wang, X},
title = {Telomere Shortening in Interstitial Lung Disease: Challenges and Promises.},
journal = {The clinical respiratory journal},
volume = {19},
number = {7},
pages = {e70103},
pmid = {40629711},
issn = {1752-699X},
support = {22Y11901300//The Project of Science and Technology Commission of Shanghai Municipality/ ; 21Y11901400//The Project of Science and Technology Commission of Shanghai Municipality/ ; 20Y11911600//The Project of Science and Technology Commission of Shanghai Municipality/ ; 81801601//National Natural Science Foundation of China/ ; 82070102//National Natural Science Foundation of China/ ; 82270114//National Natural Science Foundation of China/ ; 22XD1422700//Program of Shanghai Academic Research Leader/ ; },
mesh = {Humans ; *Lung Diseases, Interstitial/genetics/diagnosis/therapy ; *Telomerase/genetics/metabolism ; *Telomere Shortening/genetics ; *Telomere/genetics/metabolism ; Prognosis ; Mutation ; Genetic Therapy/methods ; Diagnosis, Differential ; },
abstract = {Interstitial lung disease (ILD) is a group of diseases involving diffuse pulmonary parenchymal lesions and alveolar inflammation and interstitial fibrosis. Telomeres are repetitive DNA sequences at the end of chromosomes to maintain structural integrity and telomerase can prevent telomere shortening. Telomerase abnormalities such as related gene mutations lead to decrease in telomerase activity and telomere shortening. It has been proven that telomere shortening and telomerase abnormalities are related to the occurrence and development of ILD. Telomere shortening occurs in different types of ILD patients and is associated with prognosis. Gene therapy targeting telomerase exhibits therapeutic potential. The paper elaborates on the progress of telomere shortening in the diagnosis, differential diagnosis, treatment, and prognosis of ILD in recent years, in order to demonstrate its potential and promises and to be helpful for clinical diagnosis and treatment.},
}

Humans
*Lung Diseases, Interstitial/genetics/diagnosis/therapy
*Telomerase/genetics/metabolism
*Telomere Shortening/genetics
*Telomere/genetics/metabolism
Prognosis
Mutation
Genetic Therapy/methods
Diagnosis, Differential

@article {pmid40628895,
year = {2025},
author = {Ishii, A and Takekawa, D and Kinoshita, H and Uchida, S and Masuda, O and Shirasaki, M and Noto, K and Nikaido, Y and Kushikata, T and Hirota, K},
title = {Relationship between telomere length and postoperative delirium: a single center prospective observational pilot study.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {24390},
pmid = {40628895},
issn = {2045-2322},
mesh = {Humans ; Male ; Female ; Aged ; Pilot Projects ; Prospective Studies ; *Delirium/genetics/etiology ; *Postoperative Complications/genetics ; *Telomere/genetics ; Aged, 80 and over ; Risk Factors ; Intensive Care Units ; },
abstract = {Shorter telomere length (TL) and postoperative delirium (POD) are associated with aging and inflammation. We hypothesized that shorter TL may predict POD development. This pilot study investigated whether preoperative TL can predict POD occurrence. This single-center, prospective, observational study included 50 patients aged > 65 years scheduled for postoperative intensive care unit stay ≥ 2 days. Patients with Intensive Care Delirium Screening Checklist scores ≥ 4 were categorized into the POD group. Multivariable logistic regression analyses evaluated preoperative TL as a predictor of POD. Ten patients developed POD (POD group) while 40 did not (non-POD group). Preoperative TL showed no significant difference between groups (POD vs. non-POD: 296,502 vs. 327,884 RLU/µg DNA, p = 0.104). However, multivariable analyses revealed that preoperative TL ≥ 309,110 RLU/µg DNA significantly associated with decreased POD risk after adjusting for age (aOR: 0.132; 95% CI: 0.022-0.799; p = 0.047) and preoperative MMSE score (aOR: 0.153; 95% CI: 0.028-0.851; p = 0.032). Shorter preoperative TL was associated with POD development after adjusting for age and preoperative cognitive function. Future studies with larger sample sizes are needed to confirm these associations.},
}

Humans
Male
Female
Aged
Pilot Projects
Prospective Studies
*Delirium/genetics/etiology
*Postoperative Complications/genetics
*Telomere/genetics
Aged, 80 and over
Risk Factors
Intensive Care Units

@article {pmid40627828,
year = {2025},
author = {Saraswati, S and Martínez, P and Serrano, R and Mejías, D and Graña-Castro, O and Díaz, RÁ and Flores, JM and Blasco, MA},
title = {Telomere Dysfunction in Renal Tubular Epithelial Cells Leads to Kidney Fibrosis.},
journal = {Journal of the American Society of Nephrology : JASN},
volume = {},
number = {},
pages = {},
doi = {10.1681/ASN.0000000771},
pmid = {40627828},
issn = {1533-3450},
abstract = {BACKGROUND: Renal tubular epithelial cells are the critical mediators of kidney fibrogenesis. Telomere dysfunction has been associated with kidney injury and fibrosis. However, the role of telomere dysfunction specifically in renal tubular epithelial cells in the onset and progression of kidney fibrosis remains poorly understood. TRF1 is a critical component of the telomeric protective complex known as shelterin and its deficiency results in telomere dysfunction.

METHODS: To investigate the impact of telomere dysfunction on kidney injury and fibrosis, we generated mice depleted for the shelterin component TRF1 specifically in renal tubular epithelial cells.

RESULTS: Genetic ablation of Trf1 caused decline in kidney function accompanied by increased tubular injury and tubulointerstitial fibrosis eight weeks after TRF1 depletion, concomitant with excessive accumulation of extracellular matrix, cell cycle arrest at G2/M phase, and telomeric damage. Trf1Δ/Δ mice activated regenerative repair mechanisms, supporting proliferation-mediated telomere shortening in renal tubular epithelial cells. At humane endpoint, Trf1Δ/Δ mice displayed elevated urinary albumin-to-creatinine ratio (UACR), associated with augmented interstitial fibrosis and tubular atrophy eventually leading to chronic kidney disease. At the mechanistic level, we reported the unprecedented finding that Trf1 deletion upregulates the Ras-Raf-Mek-Erk, PI3k/Akt/mTOR, and p38 pathways.

CONCLUSIONS: Our study underlies a role of renal tubular epithelial cells in the development and progression of kidney fibrosis and chronic kidney disease induced by telomere dysfunction.},
}

@article {pmid40624280,
year = {2025},
author = {In, S and Renck Nunes, P and Valador Fernandes, R and Lingner, J},
title = {TERRA R-loops trigger a switch in telomere maintenance towards break-induced replication and PRIMPOL-dependent repair.},
journal = {The EMBO journal},
volume = {},
number = {},
pages = {},
pmid = {40624280},
issn = {1460-2075},
support = {310030_214833//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)/ ; 205601//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (SNF)/ ; none//Boehringer Ingelheim Fonds (BIF)/ ; },
abstract = {TERRA long noncoding RNAs associate with telomeres post transcription through base-pairing with telomeric DNA forming R-loop structures. TERRA regulates telomere maintenance but its exact modes of action remain unknown. Here, we induce TERRA transcription and R-loop formation in telomerase-expressing cells and determine that TERRA R-loop formation requires non-redundant functions of the RAD51 DNA recombinase and its enhancer RAD51AP1. TERRA R-loops interfere with semiconservative DNA replication, promoting telomere maintenance by a homology-directed repair (HDR) mechanism known as break-induced replication (BIR), which ensures telomere maintenance in ALT cancer cells. In addition, TERRA induces PRIMPOL-dependent repair, which can initiate DNA synthesis de novo downstream of replication obstacles. PRIMPOL acts in parallel to BIR for telomere maintenance of TERRA-overexpressing cells, promoting their survival. Similarly, we find that PRIMPOL depletion is synthetic-lethal with BIR deficiency in U2OS ALT cancer cells. Therefore, TERRA R-loops by themselves are sufficient to induce ALT-typical telomere repair mechanisms, in the absence of other ALT-typical telomeric chromatin changes.},
}

@article {pmid40624070,
year = {2025},
author = {Li, C and Yuan, Y and Nie, Z and Wu, T and Wang, Z and Qiao, J and Deng, Z and Wang, X and Xu, D and Wang, X and Cao, S and Li, B and An, Z and Wu, W and Jin, Z and Huang, H and Hu, W and Zhou, Y and Cheng, H},
title = {The haplotype-resolved telomere-to-telomere genome and OMICS analyses reveal genetic responses to tapping in rubber tree.},
journal = {Nature communications},
volume = {16},
number = {1},
pages = {6255},
pmid = {40624070},
issn = {2041-1723},
mesh = {*Hevea/genetics/metabolism ; *Haplotypes/genetics ; *Telomere/genetics ; *Genome, Plant ; Cyclopentanes/metabolism ; Gene Expression Regulation, Plant ; Oxylipins/metabolism ; Mevalonic Acid/metabolism ; Rubber/metabolism ; Latex/biosynthesis/metabolism ; Genomics ; Plant Proteins/genetics/metabolism ; Chromosomes, Plant/genetics ; },
abstract = {Rubber tree (Hevea brasiliensis) is the primary source of natural rubber and economically important. We present the haplotype-resolved, telomere-to-telomere, gap-free genome assembly of the cultivar CATAS 7-33-97, with both haplotypes containing complete telomeric and centromeric regions. Structural variations, including a 32.71 Mb inversion on chromosome 8, are identified. The fully assembled 36 chromosomes enable comprehensive identification of rubber biosynthesis genes and their allele-specific expression. By integrating transcriptomic and metabolomic data, we reconstruct the rubber biosynthesis pathway and confirm the mevalonate (MVA) pathway as the major carbon source for rapid latex regeneration during tapping. Jasmonic acid (JA) plays a key role in promoting rubber yield by enhancing biosynthetic activity in response to mechanical wounding. We propose a model where JA-induced myelocytomatosis proteins 2 activate mevalonate kinase 1 expression, boosting MVA synthesis and rubber production. These findings provide insights into rubber tree genomics and its molecular response to tapping.},
}

*Hevea/genetics/metabolism
*Haplotypes/genetics
*Telomere/genetics
*Genome, Plant
Cyclopentanes/metabolism
Gene Expression Regulation, Plant
Oxylipins/metabolism
Mevalonic Acid/metabolism
Rubber/metabolism
Latex/biosynthesis/metabolism
Genomics
Plant Proteins/genetics/metabolism
Chromosomes, Plant/genetics

@article {pmid40622944,
year = {2025},
author = {Coudrieu, O and Ouedraogo, ZG and Gallot, D and Delabaere, A and Veronese, L and Eymard-Pierre, E and Tchirkov, A and Goumy, C},
title = {Association between shortened maternal and fetal telomere length and abnormal fetal development.},
journal = {PloS one},
volume = {20},
number = {7},
pages = {e0327724},
pmid = {40622944},
issn = {1932-6203},
mesh = {Humans ; Female ; Pregnancy ; Adult ; *Fetal Development/genetics ; *Fetus/metabolism ; *Telomere/genetics ; *Telomere Shortening ; ROC Curve ; *Congenital Abnormalities/genetics ; Case-Control Studies ; },
abstract = {A number of intrinsic, maternal and environmental factors have been linked to the risk of fetal developmental anomalies. In a previous study, we showed that telomere length (TL) was notably reduced in amniotic fluid when the fetus exhibited a developmental anomaly. In this new study, we measured the fetal and maternal TL for 75 evolutive pregnancies with congenital malformation. We also measured the TL of 50 pregnant women without fetal anomalies and 50 non-pregnant control women who had at least one child with normal development. In fetal samples, telomeres were significantly shortened in cases with congenital anomalies compared to controls (n = 93) (P < 0.0001). Interestingly, age-adjusted maternal TL was also significantly reduced in these cases (P < 0.01). Receiver operating characteristic (ROC) analysis showed that maternal TL, at the optimal cut-off value, identified cases of congenital anomalies with 92% specificity and 73% sensitivity. In addition, fetal and maternal TL were correlated, with 15% to 38% of the variance in fetal TL attributable to maternal TL. Telomere shortening can lead to increased sensitivity to various maternal exposure factors and may contribute to compromised organogenesis, possibly due to inadequate cell proliferation or genomic instability. Measuring maternal TL during the periconceptional period could serve as a useful predictive biomarker for assessing the risk of fetal developmental anomalies.},
}

Humans
Female
Pregnancy
Adult
*Fetal Development/genetics
*Fetus/metabolism
*Telomere/genetics
*Telomere Shortening
ROC Curve
*Congenital Abnormalities/genetics
Case-Control Studies

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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