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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@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