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Weight-inducing psychotropic treatments are risk factors for age-related diseases such as cardiovascular disorders, which are associated with both inflammation and telomere length shortening. With a longitudinal design, the present study evaluates telomere length trajectories after 1 year of weight-inducing psychotropic medication, accounting for weight changes and the inflammatory biomarker high-sensitivity C-Reactive Protein (CRP). Among 200 patients, an overall median telomere shortening of -41.2 bp was observed (p = 0.014), which is comparable with the general populations yearly telomere attrition. Linear regression showed on average -93.1 and -58.9 bp of further telomere shortening per five units of BMI for BMI values < or ≥30 kg/m2, respectively (p = 0.003 and p = 0.009, respectively). Importantly, the overall telomere shortening was predicted to be increased four-fold among patients with low baseline weight (i.e., 50 kg) and with clinically relevant weight gain (≥ 7%) after 1 year of treatment (interaction term between relevant weight gain and baseline weight: +6.3 bp, p = 0.016). Patients with relevant weight gain showed greater CRP levels (+ 49%; p = 0.016), and a telomere shortening of -36.2 bp (p = 0.010) was estimated whenever CRP level doubled. Mendelian randomization using UKBiobank data showed a causal effect of BMI on telomere shortening, notably stronger among patients receiving weight-inducing psychotropic treatments (n = 9798) than among psychiatric patients without such drugs (n = 16228) and non-psychiatric controls (n = 252932) (beta: -0.37, -0.12, -0.06, respectively; p = 0.004, p

The human telomere system is highly dynamic. Both short and long leucocyte average telomere lengths (aTL) are associated with an increased risk of cancer and early death, illustrating the complex relationship between TL and human health and the importance of assessing TL distributions with single TL analysis. A DNA microarray and telomere fluorescent in situ hybridization (DNA-array-FISH) approach was developed to measure the base-pair (bp) lengths of single telomeres. On average 32000 telomeres were measured per DNA sample with one microarray chip assaying 96 test DNA samples. Various telomere parameters, i.e. aTL and the frequency of short/long telomeres, were computed to delineate TL distribution. The intra-assay and inter-assay coefficient of variations of aTL ranged from 1.37% to 3.98%. The correlation coefficient (r) of aTL in repeated measurements ranged from 0.91 to 1.00, demonstrating high measurement precision. aTLs measured by DNA-array-FISH predicted aTLs measured by terminal restriction fragment (TRF) analysis with r ranging 0.87-0.99. A new accurate and high-throughput method has been developed to measure the bp lengths of single telomeres. The large number of single TL data provides an opportunity for an in-depth analysis of telomere dynamics and the complex relationship between telomere and age-related diseases.

The Human Genome Project was an enormous accomplishment, providing a foundation for countless explorations into the genetics and genomics of the human species. Yet for many years, the human genome reference sequence remained incomplete and lacked representation of human genetic diversity. Recently, two major advances have emerged to address these shortcomings: complete gap-free human genome sequences, such as the one developed by the Telomere-to-Telomere Consortium, and high-quality pangenomes, such as the one developed by the Human Pangenome Reference Consortium. Facilitated by advances in long-read DNA sequencing and genome assembly algorithms, complete human genome sequences resolve regions that have been historically difficult to sequence, including centromeres, telomeres, and segmental duplications. In parallel, pangenomes capture the extensive genetic diversity across populations worldwide. Together, these advances usher in a new era of genomics research, enhancing the accuracy of genomic analysis, paving the path for precision medicine, and contributing to deeper insights into human biology.

BACKGROUND: Patients with telomere biology disorders (TBD) develop hepatic disease, including hepatitis, cirrhosis, and hepatopulmonary syndrome. No specific treatment exists for TBD-related liver disease, and the role of liver transplantation (LT) remains controversial. Our study objectives were to describe the clinical characteristics, management, and outcomes in patients with TBD-related liver disease, and their LT outcomes. METHODS: Data from 83 patients with TBD-associated liver disease were obtained from 17 participating centers in the Clinical Care Consortium of Telomere-Associated Ailments and by self-report for our retrospective, multicenter, international cohort study. RESULTS: Group A (Advanced) included 40 patients with advanced liver disease. Of these, 20 underwent LT (Group AT). Group M (Mild) included 43 patients not warranting LT evaluation, none of whom were felt to be medically unfit for liver transplantation. Supplemental oxygen requirement, pulmonary arteriovenous malformation, hepatopulmonary syndrome, and higher bilirubin and international normalized ratio values were associated with Group A. Other demographics, clinical manifestations, and laboratory findings were similar between groups. Six group A patients were declined for LT; 3 died on the waitlist. Median follow-up post-LT was 2.9 years (range 0.6-13.2 y). One-year survival post-LT was 73%. Median survival post-LT has not been reached. Group AT patients had improved survival by age compared to all nontransplant patients (log-rank test p = 0.02). Of 14 patients with pretransplant hypoxemia, 8 (57%) had improved oxygenation after transplant. CONCLUSIONS: LT recipients with TBD do not exhibit excessive posttransplant mortality, and LT improved respiratory status in 57%. A TBD diagnosis should not exclude LT consideration.

Altered transcriptional and epigenetic regulation of brain cell types may contribute to cognitive changes with advanced age. Using single-nucleus multi-omic DNA methylation and transcriptome sequencing (snmCT-seq) in frontal cortex from young adult and aged donors, we found widespread age- and sex-related variation in specific neuron types. The proportion of inhibitory SST- and VIP-expressing neurons was reduced in aged donors. Excitatory neurons had more profound age-related changes in their gene expression and DNA methylation than inhibitory cells. Hundreds of genes involved in synaptic activity, including EGR1, were less expressed in aged adults. Genes located in subtelomeric regions increased their expression with age and correlated with reduced telomere length. We further mapped cell-type-specific sex differences in gene expression and X-inactivation escape genes. Multi-omic single-nucleus epigenomes and transcriptomes provide new insight into the effects of age and sex on human neurons.

Non-small cell lung cancer (NSCLC), half of which are lung adenocarcinoma (LUAD), is one of the most widely spread cancers in the world. Telomerase, which maintains telomere length and chromosomal integrity, enables cancer cells to avoid replicative senescence. When telomerase is inhibited, cancer cells' senescence began, preventing them from growing indefinitely. Cellular senescence and telomeres are intrinsically linked. As of yet, still laking a systematic study of the involvement of telomere-senescence related genes in lung adenocarcinoma development. In this study, myeloid cells were identified as the cell type which are most correlated with cellular senescence based on its highest telomere-related gene activity. GO, KEGG, GSEA and GSVA analyses were used to explore the biological function of telomere-senescence related genes in LUAD. The combined analysis of single-cell RNA-sequencing and bulk-RNA sequencing identified a gene signature composed of 14 genes which can accurately predict the prognosis of patients with LUAD. In one training and four validation sets, patients with higher Telomere Related Gene Signature (TRGS) had a worse prognosis than those with lower TRGS. Different TRGS patient groups showed varying degrees of immune cell infiltration, frequency of gene missense mutation, sensitivity to different drugs, and tumor mutation burden (TMB). Collectively, we developed a brand new signature composed of telomere-senescence related genes that can accurately predicts patients' prognosis in LUAD, which provides new insights for future research into the role of cellular senescence in LUAD. [ABSTRACT FROM AUTHOR]

• Different degrees of MS have varying effects on the susceptibility of adult rats to PTSD. • Rats subjected to short-term MS demonstrate adaptability when confronted with 'secondary stress'. • This process involves telomere shortening in the hippocampus, with notable gender differences. • The relative gene and protein expressions levels of TRF1 and TRF2 were upregulated. Early life stress (ELS) is thought to be a leading cause of mental disorders in adulthood, including PTSD. Recent studies have found that such stress has a gender and resilient specific effect on adult PTSD. This study aimed to assess emotion, and cognitive behavior, and to examine the sex differences and resilience of ELS on adult PTSD. At the same time, the expression of hippocampal telomere length and telomere repeat binding factors (TRF1 and TRF2) were detected to explore the mechanism of telomere length change. Rat offspring were separated from their dams (3 h/day or 6 h/day from PND2 ∼ PND14). Then, pups were treated with a single prolonged stress (SPS) procedure when they reached adulthood (PND80). Rats exposed early to MS and SPS showed anxiety-like and depression-like behaviors as well as impaired learning and memory. The rats exposed to MS3h showed reduced anxiety-like and depression-like behavior upon re-experiencing "secondary stress" compared to the SPS and MS6h groups. Behavioral results showed no significant gender difference. However, gender and SPS factors significantly affected telomere length and TRF1 and TRF2 gene expression in hippocampus. The SPS effect and MS*SPS interaction significantly impacted TRF1 and TRF2 protein expression. In conclusion, this study shows that MS has different effects on anxiety, depression, and cognitive memory deficits in rats experiencing "secondary stress" in adulthood and is accompanied by telomere shortening in the hippocampus. This reveals the potential impact of early MS on PTSD and provides a new perspective for further research in the field of psychological stress. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is a high-risk malignancy. Telomeres- (TRGs) and aging-related genes (ARGs) play an important role in cancer progression and prognosis. This study aimed to develop a novel prognostic model combined TRGs and ARGs signatures to predict the prognosis of patients with LUAD. Methods: LUAD patient's sample data and clinical data were obtained from public databases. The prognostic model was constructed and evaluated using the least absolute shrinkage and selection operator (LASSO), multivariate Cox analysis, time-dependent receiver operating characteristic (ROC), and Kaplan-Meier (K-M) analysis. Immune cell infiltration levels were assessed using single-sample gene set enrichment analysis (ssGSEA). Antitumor drugs with significant correlations between drug sensitivity and the expression of prognostic genes were identified using the CellMiner database. The distribution and expression levels of prognostic genes in immune cells were subsequently analyzed based on the TISCH database. Results: This study identified eight characteristic genes that are significantly associated with LUAD prognosis and could serve as independent prognostic factors, with the low-risk group demonstrating a more favorable outcome. Additionally, a comprehensive nomogram was developed, showing a high degree of prognostic predictive value. The results from ssGSEA indicated that the low-risk group had higher immune cell infiltration. Ultimately, our findings revealed that the high-risk group exhibited heightened sensitivity to the Linsitinib, whereas the low-risk group demonstrated enhanced sensitivity to the OSI-027 drug. Conclusion: The risk score exhibited robust prognostic capabilities, offering novel insights for assessing immunotherapy. This will provide a new direction to achieve personalized and precise treatment of LUAD in the future. [ABSTRACT FROM AUTHOR]

ABSTRACT Genomic projections of (mal)adaptation under future climate change, known as genomic offset, faces limited application due to challenges in validating model predictions. Individuals inhabiting regions with high genomic offset are expected to experience increased levels of physiological stress as a result of climate change, but documenting such stress can be challenging in systems where experimental manipulations are not possible. One increasingly common method for documenting physiological costs associated with stress in individuals is to measure the relative length of telomeres—the repetitive regions on the caps of chromosomes that are known to shorten at faster rates in more adverse conditions. Here we combine models of genomic offsets with measures of telomere shortening in a migratory bird, the yellow warbler (Setophaga petechia), and find a strong correlation between genomic offset, telomere length and population decline. While further research is needed to fully understand these links, our results support the idea that birds in regions where climate change is happening faster are experiencing more stress and that such negative effects may help explain the observed population declines. [ABSTRACT FROM AUTHOR]

Genome maintenance is essential for the integrity of the genetic blueprint, of which only a small fraction is transcribed in higher eukaryotes. DNA lesions occurring in the transcribed genome trigger transcription pausing and transcription‐coupled DNA repair. There are two major transcription‐coupled DNA repair pathways. The transcription‐coupled nucleotide excision repair (TC‐NER) pathway has been well studied for decades, while the transcription‐coupled homologous recombination repair (TC‐HR) pathway has recently gained attention. Importantly, recent studies have uncovered crucial roles of RNA transcripts in TC‐HR, opening exciting directions for future research. Transcription also plays pivotal roles in regulating the stability of highly specialized genomic structures such as telomeres, centromeres, and fragile sites. Despite their positive function in genome maintenance, transcription and RNA transcripts can also be the sources of genomic instability, especially when colliding with DNA replication and forming unscheduled pathological RNA:DNA hybrids (R‐loops), respectively. Pathological R‐loops can result from transcriptional stress, which may be induced by transcription dysregulation. Future investigation into the interplay between transcription and DNA repair will reveal novel molecular bases for genome maintenance and transcriptional stress‐associated genomic instability, providing therapeutic targets for human disease intervention. [ABSTRACT FROM AUTHOR]

Introduction: The changes in histone modifications are linked to the progression of benign and normal tissue to malignancy. Thus, numerous findings suggest that targeting epigenetic factors might be a focus for anti-cancer treatment. In this study, we tested the hypothesis that telomerase activator might be a potential epigenetic regulator in combatting skin cancer cell proliferation. Methods: Melanoma cell line A375 cells were treated with telomerase activator TA-65. Cell senescence assay was done to evaluate the senescence induction. Morphological changes and differences in expression of HDACs and hTERT genes were studied. Further, hyaluronidase and anti-oxidant assays were also performed. Additionally, telomerase enzyme and 20S proteasome activity was also studied. Results: Morphological changes were observed in treated cells and it is evident that telomerase activator induced cellular senescence in high concentrations. From our results, it is evident that HDAC8 and HDAC10 expression was upregulated, whereas hTERT gene expression was downregulated in treated groups. This suggests that the telomerase activator has a regulatory role in skin cancer cells proliferation by targeting the epigenetic factors. Conclusion: Targeting HDACs and hTERT in the treatment of melanoma is a prominent concern. In our current study, we highlight the most recent research, although in its initial stage, involving various epigenetic factors involved in melanoma cells proliferation. [ABSTRACT FROM AUTHOR]

Telomerase (TERT) is a ribonucleoprotein that regulates telomere length and maintains chromosomal integrity. TERT is a widely expressed protein for replicative immortality in most malignant tumours. TERT is a protein produced by cancer cells that prevents telomere shortening by adding telomere sequences beyond the Hayflick limit, allowing them to divide in an uncontrolled manner. Inhibition of the TERT enzyme is a recognised therapy for treating cancer. The basic objective of the review is to collectively represent the current scenario of treating cancer by inhibiting TERT. With a focus on the recently patented TERT inhibitors and clinical trial data released between 2015 and 2023, this review highlights the work relevant to the development of TERT inhibitors. Furthermore, recent advancements in the clinical development of TERT inhibitors, along with prospective new combinations, are also discussed. The use of TERT inhibitors in cancer therapy has been granted with great interest and significant attention by researchers along with a promising outcome in terms of therapeutic value. Several clinical trial applications and their data gave strong evidence of the use of TERT inhibitors for cancer therapy which provided target therapies, vaccine therapies, nucleoside, non‐nucleoside therapies, and so forth with reduced side effects and enhanced potency. [ABSTRACT FROM AUTHOR]

Telomeres, which are situated at the terminal ends of chromosomes, undergo a reduction in length with each cellular division, ultimately reaching a critical threshold that triggers cellular senescence. Cancer cells circumvent this senescence by utilizing telomere maintenance mechanisms (TMMs) that grant them a form of immortality. These mechanisms can be categorized into two primary processes: the reactivation of telomerase reverse transcriptase and the alternative lengthening of telomeres (ALT) pathway, which is dependent on homologous recombination (HR). Various strategies have been developed to inhibit telomerase activation in 85–95% of cancers, including the use of antisense oligonucleotides such as small interfering RNAs and endogenous microRNAs, agents that simulate telomere uncapping, expression modulators, immunotherapeutic vaccines targeting telomerase, reverse transcriptase inhibitors, stabilization of G-quadruplex structures, and gene therapy approaches. Conversely, in the remaining 5–15% of human cancers that rely on ALT, mechanisms involve modifications in the chromatin environment surrounding telomeres, upregulation of TERRA long non-coding RNA, enhanced activation of the ataxia telangiectasia and Rad-3-related protein kinase signaling pathway, increased interactions with nuclear receptors, telomere repositioning driven by HR, and recombination events between non-sister chromatids, all of which present potential targets for therapeutic intervention. Additionally, combinatorial therapy has emerged as a strategy that employs selective agents to simultaneously target both telomerase and ALT, aiming for optimal clinical outcomes. Given the critical role of anti-TMM strategies in cancer treatment, this review provides an overview of the latest insights into the structure and function of telomeres, their involvement in tumorigenesis, and the advancements in TMM-based cancer therapies. [ABSTRACT FROM AUTHOR]

Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Telomeres maintain chromosome stability, while telomerase counteracts their progressive shortening. Telomere length varies between cell types, with leukocyte telomere length (LTL) decreasing with age. Reduced telomerase activity has been linked to reproductive issues in females, such as low pregnancy rates and premature ovarian failure, with recent studies indicating correlations between telomere length in granulosa cells and IVF outcomes. Objectives: The study aims to explore the relationship between telomere length, telomerase activity, and euploid blastocyst rate in infertile women undergoing IVF/ICSI PGT-A cycles. Methods: This prospective study involves 108 patients undergoing controlled ovarian stimulation and PGT-A. Telomere length and telomerase activity were measured in peripheral mononuclear cells and granulosa cells (GC), respectively. Results: The telomere repeat copy number to single gene copy number ratio (T/S) results respectively 0.6 ± 0.8 in leukocytes and 0.7 ± 0.9 in GC. An inverse relationship was found between LTL and the patient's age (p <.01). A higher aneuploid rate was noticed in patients with short LTL, with no differences in ovarian reserve markers (p =.15), number of oocytes retrieved (p =.33), and number of MII (p = 0.42). No significant association was noticed between telomere length in GC and patients' age (p = 0.95), in ovarian reserve markers (p = 0.32), number of oocytes retrieved (p =.58), number of MII (p =.74) and aneuploidy rate (p =.65). Conclusion: LTL shows a significant inverse correlation with patient age and higher aneuploidy rates. Telomere length in GCs does not correlate with patient age or reproductive outcomes, indicating differential telomere dynamics between leukocytes and granulosa cells. [ABSTRACT FROM AUTHOR]

Objective: Knowing the important repercussions of menopause for women's health and that female longevity can be better understood through studies based on aging biomarkers, studies on the relationship between menopause and telomere shortening may help to better understand this stage of life. This study aimed to analyze what research has been produced regarding the relationship between menopause and telomere length. Methods: This integrative literature review included searches in PubMed, CINAHL, LILACS, Web of Science and Scopus databases. Four studies were selected for the final sample. Results: The findings of these studies indicate that older age for menopause and longer reproductive life (difference between age at menopause and menarche) are associated with longer telomeres, that is, with longevity. Conclusion: The relationship between menopause and telomere length is uncertain. The small number of studies included in this review, and the fact that the results indicate that the relationship between menopause and telomere length may be dependent on the stage of the menopause and race/ethnicity, suggest that additional research focusing on these variables should be carried out. [ABSTRACT FROM AUTHOR]

A 14-year boy is given a microscope by his parents. It is not a toy – but a real microscope. He deploys it to rediscover the biology he had known before, but now in a magnified world. With extraordinary intellectual gifts he then, and manifestly later becomes absorbed by the idea that all this, however mysterious at first glance, might be subject to rational understanding, with painstaking study. Thus, was the genesis of one of the greatest cell biologists of the 20th century, Joseph Grafton Gall, who died 12 September 2024, at 96. He had been professionally active up until only a few years ago. There was no one like him in the modern era of cell biology and there will not be another figure like him anytime soon. [ABSTRACT FROM AUTHOR]

Heterochromatin is an organizational property of eukaryotic chromosomes, characterized by extensive DNA and histone modifications, that is associated with the silencing of transposable elements and repetitive sequences. Maintaining heterochromatin is crucial for ensuring genomic integrity and stability during the cell cycle. During meiosis, heterochromatin is important for homologous chromosome synapsis, recombination, and segregation, but our understanding of meiotic heterochromatin formation and condensation is limited. In this review, we focus on the dynamics and features of heterochromatin and how it condenses during meiosis in plants. We also discuss how meiotic heterochromatin influences the interaction and recombination of homologous chromosomes during prophase I. [ABSTRACT FROM AUTHOR]

Background: Several studies suggest that child maltreatment (CM) is a risk factor for a wide range of adverse biological and psychological outcomes, such as cocaine use disorder (CUD). CM and CUD are independently associated with altered telomere length (TL), but the mechanisms that underpin this relationship remain unknown. The aim of this study was to examine TL changes in cocaine-addicted individuals with and without CM. Methods: This study comprised 29 cocaine-addicted individuals with a DSM-5 diagnosis of CUD and 29 healthy controls. All subjects completed questionnaires to evaluate the presence of CM (CTQ-SF) and their perceived parental care quality (PBI). Based on the responses, the CUD sample was divided into subgroups, while the control group was selected based on the absence of CM. Blood was collected from all participants, DNA was extracted, and TL was measured using quantitative real-time PCR. Results: CUD patients with a history of CM had the shortest TL among subgroups. Further, we observed a linear relationship between "paternal care" levels experienced in childhood and TL. Conclusion: These results support the association between telomere shortening with CM and drug addiction and suggest that greater parental care is a protective factor against stressors that affect TL. [ABSTRACT FROM AUTHOR]

Telomere length (TL) predicts the onset of replicative senescence, and its shortening is a limiter on the number of divisions individual somatic cells can perform. Metal-induced genotoxic events are discussed in Agency for Toxic Substances and Disease Registry's (ATSDR) toxicological profiles. In vivo and in vitro toxicological studies suggest the correlation between toxic metals and TL. However, the correlation between TL and exposure to toxic metals in human populations is unclear despite decades of observational research. We conducted a literature search within the ATSDR toxicological profiles and PubMed database for peer-reviewed articles as of 04/2023 discussing TL and metal exposure in human populations. Through review of the 272 publications meeting these criteria, we identified 25 observational studies that considered the correlation between TL and exposure to some or all of six metals: cadmium (Cd), arsenic (As), nickel (Ni), selenium (Se), lead (Pb), and cesium (Cs). Because reported effect sizes were often not comparable across studies, we performed a sign test based on the reported significance for each metal–TL correlation. We found that Cd was consistently significantly correlated with shorter telomeres (p = 0.016). However, no consistent linear relationship was observed between TL and any of the other metals considered. Exploring this association can enhance our understanding of how metal exposure may influence TL dysfunction. Our findings suggest that Cd exposure contributes to shorter TL, which may affect the DNA damage response (DDR) resulting in numerous chronic health conditions. Further, we highlight inconsistencies in findings on the correlation between metal exposure and TL across different populations and exposure levels. This suggests that correlations between some metals and TL may vary across populations, and that correlations may change at different exposure levels. Also, our findings suggest the need for further research on the potential for nonlinear relationships and non-additive effects of co-exposure to multiple hazardous metals, which could explain the inconsistencies observed across studies. The inconsistent incidences of metal–TL correlations justify additional exploration into the complex interaction between metals and TL. [ABSTRACT FROM AUTHOR]

Lithium is an established first-line treatment for bipolar disorder. Beyond its therapeutic effect as a mood stabiliser, lithium exhibits potential anti-ageing effects. This study aimed to examine the relationship between the duration of lithium use, biological ageing and mortality. The UK Biobank is an observational study of middle-aged and older adults. We tested associations between the duration of lithium use (number of prescriptions, total duration of use and duration of the first prescription period) and telomere length, frailty, metabolomic age (MileAge) delta, pulse rate and all-cause mortality. Five hundred ninety-one individuals (mean age = 57.49 years; 55% females) had been prescribed lithium. There was no evidence that the number of prescriptions (β = − 0.022, 95% CI − 0.081 to 0.037, p = 0.47), the total duration of use (β = − 0.005, 95% CI − 0.023 to 0.013, p = 0.57) or the duration of the first prescription period (β = − 0.018, 95% CI − 0.051 to 0.015, p = 0.29) correlated with telomere length. There was also no evidence that the duration of lithium use correlated with frailty or MileAge delta. However, a higher prescription count and a longer duration of use was associated with a lower pulse rate. The duration of lithium use did not predict all-cause mortality. We observed no evidence of associations between the duration of lithium use and biological ageing markers, including telomere length. Our findings suggest that the potential anti-ageing effects of lithium do not differ by the duration of use. [ABSTRACT FROM AUTHOR]

Marine turtles are iconic, globally distributed large reptiles with a largely oceanic life history that makes it difficult to characterize population demography and dynamics. This is significant because all marine turtle species are currently considered vulnerable or endangered. Knowledge of the age of individuals is central to our understanding of the life history of a species and an important consideration in the design of management and conservation strategies. Herein, we review different methods used to estimate the absolute, relative and physiological age of marine turtles, as well as their underlying hypotheses and challenges in their interpretation. We conclude that, at present, there is no validated method that establishes the absolute age of an individual from field studies. [ABSTRACT FROM AUTHOR]

Cancer is a major global health burden, causing significant economic losses and premature deaths worldwide. Maintenance of telomeric repeats by telomerase makes the cancer cells immortal. Non-nucleoside mushroom metabolites were screened for their ability to stabilize RG4 structures, making telomeres inaccessible to telomerase and inducing telomere shortening in cancer cells. Selected mushroom metabolites, namely, Sterenin M, Melleolide K, and Zhankuic Acid A were docked with RG4 using the AutoDock Vina and evaluated for non-covalent interactions. These compounds were found to have strong binding affinity and manifested a set of molecular interactions with RG4. To assess the stability of complexes, state-of-the-art molecular dynamics simulations were carried out using the GROMACS 2018.7 software suite with the AMBER99SB-ILDN force field on 250 nanoseconds. Molecular docking and MD simulations revealed the strong interaction patterns between RG4 and the selected metabolites at the atomic level followed by binding free energy calculations. The results suggest that all three metabolites have the potential to be developed into therapeutic agents for cancer treatment. Further in vitro and in vivo studies are needed to assess these compounds' toxicity, efficacy, and dosage. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease (CVD) includes a range of conditions affecting the brain's blood vessels, which can result in reduced blood flow to brain tissue. The most common manifestation of CVD is stroke, the second leading cause of death and the third leading cause of disability worldwide. Major risk factors for CVD encompass gender, age, smoking, hypertension, diabetes, physical inactivity, obesity, alcohol consumption, and metabolic syndrome. Research suggests a link between telomere length and an increased risk of CVD, particularly in ischemic stroke cases. This review highlights key findings on the relationship between telomere length and CVD, underscoring its clinical importance. The analysis utilizes scientific literature from PubMed, Scopus, and SciELO up to 2024. Results show that shorter telomere length is associated with various types of CVD, including stroke, ischemic stroke, hemorrhagic stroke, and cardioembolic stroke. Some studies propose that telomere length measurement could be a valuable biomarker for CVD, potentially improving prevention, diagnosis, and management strategies. [ABSTRACT FROM AUTHOR]

To study telomere maintenance mechanism (TMM) activation during malignant transformation, we compared neurofibroma (NF) and malignant peripheral nerve sheath tumor (MPNST) in the same patient with type-1 neurofibromatosis (NF1), a total of 20 NF-MPNST pairs in 20 NF1 patients. These comparisons minimized genetic bias and contrasted only changes associated with malignant transformation, while subtracting changes that developed upon the transformation of normal cells to the benign tumor. TGF-β superfamily genes were found to activate the PAX and SOX transcription factors, leading to TMM activation. BMPER activates PAX6 through BMP2 and PAX7 through BMP4; BMP15 activates SOX14; and INHBC activates PAX9 and SOX14. The activated PAX and SOX genes sequentially establish the core architecture of the RAD52-dependent alternative lengthening of telomeres (ALT). Specifically, PAX7 activates the recombinase (RAD52) and a negative regulator (SLX4IP). PAX6 and SOX14 activate positive regulators (BLM and BRCA2, respectively). PAX9 and SOX14 activate RAD9B and FEN1, which are responsible for the stability of homologous recombination intermediates and increase, together with RAD52, the telomere length. Telomere elongation achieved by the activation of PAX7 and PAX9 is associated with a poor prognosis. We demonstrated that TGF-β superfamily-induced transcriptional activation pathways activated the RAD52-dependent ALT during malignant transformation of MPNSTs. [ABSTRACT FROM AUTHOR]

Shortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown. What is the clinical impact of TL testing on the management of ILD? Patients were evaluated in the Columbia University ILD clinic and underwent Clinical Laboratory Improvement Amendments-certified TL testing by flow cytometry and fluorescence in situ hybridization (FlowFISH) as part of clinical treatment. Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared with research quantitative polymerase chain reaction (qPCR) TL measurement. A total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR, 2.00; 95% CI, 1.27-3.32). TL testing led to clinical treatment changes for 35 patients (32%), most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n = 34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 patients (29%). Inclusion of TL testing below the 1st percentile helped reclassify eight of nine variants of uncertain significance into actionable findings. The quantitative polymerase chain reaction test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays. Incorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants. [ABSTRACT FROM AUTHOR]

There is growing interest in telomere length as an indicator of current and future health. Although early childhood is a period of rapid telomere attrition, little is known about the factors that influence telomere biology during this time. Adult research suggests that telomere length is influenced by psychological characteristics. This study's goal was to test associations among repeated measures of temperament and telomere length in a community sample of children (N = 602; 52% male, 73% non-Hispanic White, middle-to-high socioeconomic status) from infancy to age 3 years. Relative telomere length was assessed from DNA in saliva samples collected at infancy (M = 8.4 months), 2 years (M = 24.9 months), and 3 years (M = 37.8 months). Temperament was assessed via maternal report questionnaires administered at infancy (Infant Behavior Report Questionnaire–Revised) and ages 2 and 3 years (Early Childhood Behavior Questionnaire). Temperament was operationalized in two ways: using the established domains of negative affectivity, surgency/extraversion, and regulation/effortful control and using person-centered scores that identified three groups of children with similar profiles across domains (emotionally and behaviorally regulated; emotionally and behaviorally dysregulated; introverted and overcontrolled). Analyses revealed that greater regulation/effortful control was associated with longer telomere length across time points. Additionally, higher surgency/extraversion, beginning in infancy, was associated with decreased rate of telomere attrition. There were no sex differences in the relations between temperament and telomere measures. These findings suggest that, as early as infancy, temperament may influence telomere biology, with a potential protective effect of positive temperament characteristics on telomere erosion. Public Significance Statement: This study suggests that positive temperament characteristics may buffer telomere erosion in early childhood. Telomere erosion is a measure of cellular aging that may contribute to many diseases across the lifespan. Identifying factors in early life that influence telomeres may enhance our understanding of the origins of health and disease and our ability to identify at-risk individuals and to develop targeted, effective interventions that maximize health outcomes across the lifespan. [ABSTRACT FROM AUTHOR]

Objective: Silicosis is a pneumoconiosis characterized by fibrosis of the lung parenchyma caused by the inhalation of silica particles. Silica dust inhalation is associated with inflammation and induction of oxidative stress in the lungs. This oxidative stress affects telomeres, which are short tandem DNA repeats that cap the end of linear chromosomes. We aimed to determine whether telomere length (TL) correlates with silicosis or severity of silicosis in silica-exposed workers in Brazil. Methods: We included 200 men in southeastern Brazil: 100 with silicosis and 100 who had not been exposed to silica. We extracted DNA from buccal cells and assessed TL by multiplex quantitative polymerase chain reaction. Results: The median TL was significantly shorter in the patients with silicosis than in the unexposed controls (p < 0.0001), although it did not differ between the patients with simple silicosis and those with complicated silicosis (p = 0.961). We also found that, in patients with silicosis, TL was influenced by smoking (p = 0.034) and by a history of personal protective equipment use in the workplace (p = 0.002). Conclusions: Silica exposure appears to have an impact on TL, which was found to be shorter in patients with silicosis than in unexposed controls. Further studies are needed in order to confirm the impact that oxidative stress caused by silica inhalation has on telomeres. [ABSTRACT FROM AUTHOR]

Abstract Previous studies have reported an association between telomere length and non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the involvement of alternative lengthening of telomere-related genes (ALTRGs) in the pathology of NAFLD, construct a risk signature, and evaluate both treatment and prognosis. Three NAFLD datasets (GSE48452, GSE89632, and GSE63067) were collected from the GEO database and merged into combined GEO datasets. ALTRGs were collected from GeneCards and PubMed databases. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. This study employed a support vector machine algorithm and least absolute shrinkage and selection operator regression analysis to identify key genes for constructing a diagnostic model. High- and low-risk groups were identified from the combined GEO datasets using the diagnostic model. Gene set enrichment analysis, regulatory network analysis, and intergroup immune infiltration analysis were performed. This study identified the key genes using receiver operating characteristic and Friends analysis. Expression of these genes was validated in a mouse model of NAFLD. Twenty-five genes were differentially expressed, with a positive correlation between FOS and EGR1 and a negative correlation between MYC and CEBPA. A diagnostic model was constructed using 12 genes, and high- and low-risk groups were identified. CAMK2G, ERBB2, FOSB, WT1, and CEBPA showed certain accuracy, and their expression levels were significantly different in the model. Immune infiltration analysis between the risk groups revealed that six immune cells were statistically significant. This includes a strong negative interaction between type 2 T helper cells and SPHK2 in the high-risk group. These findings suggest that ALTRDEGs are potential therapeutic targets and prognostic indicators for NAFLD. However, further investigations are required to elucidate the specific underlying mechanisms.

Galliformes and Anseriformes are two branches of the Galloanserae group, basal to other Neognathae. In contrast to Galliformes, Anseriformes have not been thoroughly researched by cytogenetic methods. This report is focused on representatives of Anseriformes and the evolution of their chromosome sets. Detailed cytogenetic analysis (G-banding, C-banding, and fluorescence in situ hybridization) was performed on three duck species: the northern pintail (Anas acuta, 2n = 80), the mallard (A. platyrhynchos, 2n = 80), and the common goldeneye (Bucephala clangula, 2n = 80). Using stone curlew (Burhinus oedicnemus, 2n = 42, Charadriiformes) chromosome painting probes, we created homology maps covering macrochromosomes and some microchromosomes. The results indicated a high level of syntenic group conservation among the duck genomes. The two Anas species share their macrochromosome number, whereas in B. clangula, this number is increased due to fissions of two ancestral elements. Additionally, in this species, the presence of massive heterochromatic blocks in most macroautosomes and sex chromosomes was discovered. Localization of clusters of ribosomal DNA and telomere repeats revealed that the duck karyotypes contain some microchromosomes that bear ribosomal RNA genes and/or are enriched for telomere repeats and constitutive heterochromatin. Dot plot (D-GENIES) analysis confirmed the established view about the high level of syntenic group conservation among Anatidae genomes. The new data about the three Anatidae species add knowledge about the transformation of macro- and sex chromosomes of Anseriformes during evolution.

Abstract To study telomere maintenance mechanism (TMM) activation during malignant transformation, we compared neurofibroma (NF) and malignant peripheral nerve sheath tumor (MPNST) in the same patient with type-1 neurofibromatosis (NF1), a total of 20 NF-MPNST pairs in 20 NF1 patients. These comparisons minimized genetic bias and contrasted only changes associated with malignant transformation, while subtracting changes that developed upon the transformation of normal cells to the benign tumor. TGF-β superfamily genes were found to activate the PAX and SOX transcription factors, leading to TMM activation. BMPER activates PAX6 through BMP2 and PAX7 through BMP4; BMP15 activates SOX14; and INHBC activates PAX9 and SOX14. The activated PAX and SOX genes sequentially establish the core architecture of the RAD52-dependent alternative lengthening of telomeres (ALT). Specifically, PAX7 activates the recombinase (RAD52) and a negative regulator (SLX4IP). PAX6 and SOX14 activate positive regulators (BLM and BRCA2, respectively). PAX9 and SOX14 activate RAD9B and FEN1, which are responsible for the stability of homologous recombination intermediates and increase, together with RAD52, the telomere length. Telomere elongation achieved by the activation of PAX7 and PAX9 is associated with a poor prognosis. We demonstrated that TGF-β superfamily-induced transcriptional activation pathways activated the RAD52-dependent ALT during malignant transformation of MPNSTs.

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

OBJECTIVE: To examine changes in leukocyte telomere length (LTL) during and after a behavioural weight control program for children with obesity. METHODS: We measured LTL among a cohort of 158 children 8-12 years of age with a body mass index greater than or equal to the 95th percentile for age and sex. Children were 55% female, 29% white, 52% Latinx, 8% Asian and 11% Pacific Islander, other or multiethnic. All children participated in a 6-month, family-based, group behavioural weight control program and were assessed before treatment, after treatment and 1 year after the end of treatment. To test the sample population slope of LTL over the intervention and maintenance time periods, we fit spline mixed-effect regression models. RESULTS: LTL increased an average of 0.09 T/S units per year (95% confidence interval [CI] 0.04 to 0.13; p = 0.0001) during the weight control program intervention period, followed by an average decline of -0.05 T/S units per year (95% CI -0.08 to -0.03; p

Viruses are the most abundant biological entities in the world's oceans, where they play important ecological and biogeochemical roles. Metagenomics is revealing new groups of eukaryotic viruses, although disconnected from known hosts. Among these are the recently described mirusviruses, which share some similarities with herpesviruses.1 50 years ago, "herpes-type" viral particles2 were found in a thraustochytrid member of the labyrinthulomycetes, a diverse group of abundant and ecologically important marine eukaryotes,3,4 but could not be further characterized by methods then available. Long-read sequencing has allowed us to connect the biology of mirusviruses and thraustochytrids. We sequenced the genome of the genetically tractable model thraustochytrid Aurantiochytrium limacinum ATCC MYA-1381 and found that its 26 linear chromosomes have an extraordinary configuration. Subtelomeric ribosomal DNAs (rDNAs) found at all chromosome ends are interspersed with long repeated sequence elements denoted as long repeated-telomere and rDNA spacers (LORE-TEARS). We identified two genomic elements that are related to mirusvirus genomes. The first is a ∼300-kbp episome (circular element 1 [CE1]) present at a high copy number. Strikingly, the second, distinct, mirusvirus-like element is integrated between two sets of rDNAs and LORE-TEARS at the left end of chromosome 15 (LE-Chr15). Similar to metagenomically derived mirusviruses, these putative A. limacinum mirusviruses have a virion module related to that of herpesviruses along with an informational module related to nucleocytoplasmic large DNA viruses (NCLDVs). CE1 and LE-Chr15 bear striking similarities to episomal and endogenous latent forms of herpesviruses, respectively, and open new avenues of research into marine virus-host interactions.

Advances in long-read sequencing and assembly now mean that individual labs can generate phased genomes that are more accurate and more contiguous than the original human reference genome. With declining costs and increasing democratization of technology, we suggest that complete genome assemblies, where both parental haplotypes are phased telomere to telomere, will become standard in human genetics. Soon, even in clinical settings where rigorous sample-handling standards must be met, affected individuals could have reference-grade genomes fully sequenced and assembled in just a few hours given advances in technology, computational processing, and annotation. Complete genetic variant discovery will transform how we map, catalog, and associate variation with human disease and fundamentally change our understanding of the genetic diversity of all humans.

BackgroundStudies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD).MethodsA retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure.ResultsThe discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL

Rare germline variation in regulator of telomere elongation helicase 1 (RTEL1) is associated with telomere biology disorders (TBDs). Biallelic RTEL1 variants result in childhood onset dyskeratosis congenita and Hoyeraal‐Hreidarsson syndrome whereas heterozygous individuals usually present later in life with pulmonary fibrosis or bone marrow failure. We compiled all TBD‐associated RTEL1 variants in the literature and assessed phenotypes and outcomes of 44 individuals from 14 families with mono‐ or biallelic RTEL1 variants enrolled in clinical trial NCT00027274. Variants were classified by adapting ACMG‐AMP guidelines using clinical information, telomere length, and variant allele frequency data. Compared with heterozygotes, individuals with biallelic RTEL1 variants had an earlier age at diagnosis (median age 35.5 vs. 5.1 years, p < 0.01) and worse overall survival (median age 66.5 vs. 22.9 years, p < 0.001). There were 257 unique RTEL1 variants reported in 47 publications, and 209 had a gnomAD minor allele frequency <1%. Only 38.3% (80/209) met pathogenic/likely pathogenic criteria. Notably, 8 of 209 reported disease‐associated variants were benign or likely benign and the rest were variants of uncertain significance. Given the considerable differences in outcomes of TBDs associated with RTEL1 germline variants and the extent of variation in the gene, systematic functional studies and standardization of variant curation are urgently needed to inform clinical management. [ABSTRACT FROM AUTHOR]

Background: Optimizing DNA extraction for the preservation of telomere length – as a biomarker for ageing and vari-ous diseases – is highly important. Long-term stored blood samples are considered essential resources for genetic studies. In this study, different lysis buffers were used along with CTAB extraction buffer to inves-tigate the quality of extracted DNA and the effect of its accompanying inhibitors on quantitative PCR (q-PCR) in telomere studies. Materials and Methods: DNA extraction was performed using six RBC lysis buffers and CTAB-based extraction buffer. DNA integrity was evaluated by gel electrophoresis, quantity by absorbance at 260 nm and its purity with expected values of 1.8 and 2-2.2 for the ratios of A260/A280 and A260/A230. The quantitative effect of each buffer in q-PCR and the repeatability of the results were assessed by calculating the reaction efficiency, coefficient of determination (R2), and percentage of coefficient of variation (%CV). Results: Buffer number 5 (10 mM Tris-HCl, pH 7.6, 50 mM NaCl) yielded the highest amount of DNA extraction (324.93 ng/ml, %CV 11.53). All the extracted DNA samples were pure, as indicated by the acceptable A260/A280 and A260/A230ratios (p>0.05). Gel analysis revealed that the extracted DNA of all the buffers ex-cept one was intact. The DNA molecule extracted with buffer number 1 (155 mM NH4Cl, 10 mM KHCO3, and 5 mM EDTA) showed the best performance in q-PCR for HBG gene (efficiency=0.126, R2=0.97) and telomere (efficiency=0.99, R2=0.99). Conclusion: The DNA molecule extracted from frozen blood samples by buffer number 1 showed the least q-PCR inhibition for telomere study.

Abstract Background Biological aging is a complex process influenced by various factors, including reproductive status and castration. This study aimed to evaluate the impact of castration on biological aging in dogs. Method Fifteen male crossbred dogs were randomly divided into a sham-operation control group (n = 5) and a castrated group (n = 10). Blood samples were collected at weeks 0, 4, 8, 12, 16, and 18 post-surgery. Malondialdehyde (MDA as indicator of Lipid peroxidation), C-reactive protein (as an indicator of inflammation), telomere length, mitochondrial DNA (mtDNA) copy number, and the expression of age-related (P16, P21, TBX2) and telomerase-related (TERT) genes were assessed in blood samples. Results Plasma MDA levels were higher in the control group at weeks 16 and 18, while CRP levels were higher only at week 18. Telomere length and mtDNA copy number were lower in the control group at week 18. Gene expression analysis showed that P16 was lower in the control group at weeks 8 and 12, P21 and TERT were lower at weeks 16 and 18, and TBX2 was lower at weeks 16 and 18. The TBX2/P16 ratio was lower in the control group at weeks 16 and 18 but higher at week 12, while the TBX2/P21 ratio did not differ between groups. Conclusion Castration appears to have a protective effect against biological aging in dogs, as evidenced by lower lipid peroxidation, inflammation, and age-related changes in telomere length, mtDNA copy number, and gene expression.

Abstract Background Telomeres are a critical component of chromosome integrity and are essential to the development of cancer and cellular senescence. The regulation of breast cancer by telomere-associated lncRNAs is not fully known, though. The goals of this study were to describe predictive telomere-related LncRNAs (TRL) in breast cancer and look into any possible biological roles for these RNAs. Methods We obtained RNA-seq data, pertinent clinical data, and a list of telomere-associated genes from the cancer genome atlas and telomere gene database, respectively. We subjected differentially expressed TRLs to co-expression analysis and univariate Cox analysis to identify a prognostic TRL. Using LASSO regression analysis, we built a prognostic model with 14 TRLs. The accuracy of the model’s prognostic predictions was evaluated through the utilization of Kaplan-Meier (K-M) analysis as well as receiver operating characteristic (ROC) curve analysis. Additionally, immunological infiltration and immune drug prediction were done using this model. Patients with breast cancer were divided into two subgroups using cluster analysis, with the latter analyzed further for variations in response to immunotherapy, immune infiltration, and overall survival, and finally, the expression of 14-LncRNAs was validated by RT-PCR. Results We developed a risk model for the 14-TRL, and we used ROC curves to demonstrate how accurate the model is. The model may be a standalone prognostic predictor for patients with breast cancer, according to COX regression analysis. The immune infiltration and immunotherapy results indicated that the high-risk group had a low level of PD-1 sensitivity and a high number of macrophages infiltrating. In addition, we’ve discovered a number of small-molecule medicines with considerable for use in treating high-risk groups. The cluster 2 subtype showed the highest immune infiltration, the highest immune checkpoint expression, and the worst prognosis among the two subtypes defined by cluster analysis, which requires more attention and treatment. Conclusion As a possible biomarker, the proposed 14-TRL signature could be utilized to evaluate clinical outcomes and treatment efficacy in breast cancer patients.

Abstract Background Telomeric repeat arrays at the ends of chromosomes are highly dynamic in composition, but their repetitive nature and technological limitations have made it difficult to assess their true variation in genome diversity surveys. Results We have comprehensively characterized the sequence variation immediately adjacent to the canonical telomeric repeat arrays at the very ends of chromosomes in 74 genetically diverse Arabidopsis thaliana accessions. We first describe several types of distinct telomeric repeat units and then identify evolutionary processes such as local homogenization and higher-order repeat formation that shape diversity of chromosome ends. By comparing largely isogenic samples, we also determine repeat number variation of the degenerate and variant telomeric repeat array at both the germline and somatic levels. Finally, our analysis of haplotype structure uncovers chromosome end-specific patterns in the distribution of variant telomeric repeats, and their linkage to the more proximal non-coding region. Conclusions Our findings illustrate the spectrum of telomeric repeat variation at multiple levels in A. thaliana—in germline and soma, across all chromosome ends, and across genetic groups—thereby expanding our knowledge of the evolution of chromosome ends.

Abstract Migraine, common in individuals under 50 years, is linked to oxidative stress. The association between telomere length shortening and migraine, along with potential age-related influences, has not been comprehensively studied. This cross-sectional study included data from 6169 participants in the National Health and Nutrition Survey (NHANES) from 1999 to 2002, encompassing information on peripheral blood leukocyte telomere length, severe headache or migraine, and potential confounders. Stratifying by age (20–50 years, > 50 years), we employed multivariable logistic regression, restricted cubic splines and interaction test to investigate age-influenced telomere length in relation to migraine. In participants aged 20–50 years, the odds ratio (OR) for migraine in the shortest telomere length group T1 (0.39–0.89) was 1.35 (95% confidence interval [95% CI] 1.01, 1.79) compared to the longest group T3 (1.10–9.42), whereas in those aged > 50 years, the OR of T1 was 0.93 (95% CI 0.60, 1.43). Additionally, telomere length and age interacted in the development of migraine (p for interaction: 0.010). In individuals aged 20–50, an L-shaped relationship was found between telomere length and migraine, with an inflection point at 1.02T/S ratio. The OR was 9.34 (95% CI 1.56, 55.99) for telomere lengths