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Telomerase reverse transcriptase (TERT) promoter mutations (TPMs) are frequently found in different cancer types, including ∼70% of sun-exposed skin melanomas. In melanoma, TPMs are among the earliest mutations and can be present during the transition from nevus to melanoma. However, the specific factors that contribute to the selection of TPMs in certain nevi subsets are not well understood. To investigate this, we analyzed a group of dysplastic nevi (DN) by sequencing genes commonly mutated in melanocytic neoplasms. We examined the relationship between the identified mutations, patient age, telomere length, histological features, and the expression of p16. Our findings reveal that TPMs are more prevalent in DN from older patients and are associated with shorter telomeres. Importantly, these TPMs were not found in nevi with BRAF V600E mutations. Conversely, DN with BRAF V600E mutations were observed in younger patients, had longer telomeres and a higher proportion of p16-positive cells. This suggests that these nevi arrest growth independently of telomere shortening through a mechanism known as oncogene-induced senescence (OIS). These characteristics extend to melanoma-sequencing datasets, where melanomas with BRAF V600E mutations were more likely to have a CDKN2A inactivation, overriding OIS. In contrast, melanomas without BRAF V600E mutations showed a higher frequency of TPMs. Our data imply that TPMs are selected to bypass replicative senescence (RS) in cells that were not arrested by OIS. Overall, our results indicate that a subset of melanocytic neoplasms face constraints from RS, while others encounter OIS and RS. The order in which these barriers are overcome during progression to melanoma depends on the mutational context.

Introduction: Cancer is a genetic disease that affects people worldwide, and breast cancer is the most common cancer in women. Studies have been conducted on molecular parameters to predict tumor behavior and develop therapeutic strategies. Telomeres, which are at the end of chromosomes, have been studied for their relationship with breast cancer, but more research is needed to understand their role in the disease. Circulating‐free DNA (cfDNA) is DNA that is free in the bloodstream and is considered a promising target for early cancer detection, treatment response monitoring, and prognosis assessment. This study is aimed at comparing cfDNA telomere length of breast cancer patients and healthy individuals and analyzing the impact of neoadjuvant chemotherapy on telomere length in cfDNA. Materials and Methods: Blood samples were collected from 33 breast cancer patients undergoing neoadjuvant chemotherapy before and after treatment. The quantitative PCR method is used to measure the average telomere lengths. Results: This study found that the telomere length of cfDNA in breast cancer patients before and after treatment is significantly shorter than in the control group. Neoadjuvant chemotherapy is found to shorten the cfDNA telomere length, especially in the treatment‐responsive group. Conclusion: Our study suggests that telomere length in cfDNA may be a useful biomarker for predicting therapy response and possible reoccurrence of the disease in breast cancer patients. [ABSTRACT FROM AUTHOR]

Bipolar disorder (BD) is hypothesized to be associated with accelerated biological aging. Telomere length (TL) is a biomarker of aging, and although TL decreases with each cell division, the rate of telomere shortening may be affected by inflammation. We aimed to investigate whether TL is decreased in BD patients and to determine the association between TL and inflammatory markers in such patients. 137 BD patients and 118 healthy controls (HCs) were recruited. Leukocyte TL and plasma levels of cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-8, IL-6, IL-10, transforming growth factor (TGF)-β1], C-reactive protein (CRP), and brain-derived neurotrophic factor (BDNF) were assessed. TL did not differ significantly between the BD patients and HCs after adjustment for potential confounding factors (P = 0.79). TL was significantly negatively associated with age (β = −0.007, P < 0.001). In addition, log TNF-α levels were significantly negatively associated with TL (P = 0.009), in both the BD patients (P = 0.02) and HCs (P = 0.05). We found a significant association between TNF-α levels and TL shortening in both BD patients and HCs. However, BD patients did not display increased TL shortening relative to HCs. Studies that involve larger sample sizes and control for the heterogeneity of BD participants will be needed. • Bipolar disorder patients may not have telomere length shortening • Plasma tumor necrosis factor-α levels may be associated with telomere length shortening • Bipolar disorder subtypes and mood states may not relate to telomere length shortening [ABSTRACT FROM AUTHOR]

While links between certain chronotypes and poorer health outcomes have been well established in previous studies, few studies have examined the relationship between chronotype and cellular aging. Using data from the California Teachers Study (CTS), the present study evaluates the relationship between cellular aging and chronobiology through an analysis of leukocyte telomere length (LTL) and chronotype among 817 predominantly postmenopausal women with no history of cancer and occupations not associated with night-shift work. Unconditional logistic regression models were run to estimate odds ratios (ORs) for each chronotype category, adjusted for age, ethnicity, and smoking status. Analyses were then stratified by potential modifiers to assess whether results varied among specific subgroups within the sample. Women who reported being current evening types and evening types from teen years to now were significantly less likely to have short LTL compared to women who reported being current morning types or morning types from teen years to now (OR = 0.72; 95% CI = 0.53-0.98; OR = 0.57; 95% CI = 0.39-0.84). Our results suggest that women with no history of cancer who identify as evening chronotypes may undergo decreased cellular aging compared to women in the same population who identify as morning types. Further studies on populations of postmenopausal women are warranted. [ABSTRACT FROM AUTHOR]

PurposeMethodsResultsConclusionsTo investigate whether there is a direct, age-independent association between telomere length and visual acuity decline in a large community-based cohort study.Participants older than 40 with linked leukocyte telomere length (LTL) were enrolled in NHANES. LTL was assayed using qPCR from the participants’ blood samples. Best corrected visual acuity (BCVA) of the better-seeing eye was analyzed, with visual impairment (VI) defined as BCVA ≥ 20/40. LTL was grouped into quartiles, and its association with BCVA and VI was evaluated after adjusting for covariates.Among the 4,480 enrolled participants, the weighted means of age, BCVA, and telomere length were 56.1 ± 11.9 years, 0.05 ± 0.08 logMAR, and 5,662 ± 36 base pairs, respectively. The proportion of VI was 2.6%. After adjusting for covariates including sex, ethnicity, education, family poverty income ratio, general health status, hypertension, diabetes, smoking, and body mass index, BCVA was significantly worse in participants with shorter LTL, with a significant trend (p = 0.002). However, after further adjusting for age, the association between LTL and BCVA was no longer significant, without a trend (p = 0.640). No significant association or trend between LTL and VI was found in the stepwise logistic model.No age-independent association between LTL and BCVA was found. Our study indicates LTL may not serve as a biomarker for age-related visual acuity decline. [ABSTRACT FROM AUTHOR]

This study aimed to measure relative telomere length (RTL) in blood leukocytes of advanced-stage NSCLC patients either with or without Osimertinib-induced ADRs and determine whether RTL could serve as a biomarker of Osimertinib-induced ADRs. Blood leukocytes RTL were measured in 63 advanced-stage NSCLC patients and 62 age-matched healthy controls using real-time polymerase chain reaction. In patients with advanced-stage NSCLC, RTL was significantly shorter than that in healthy controls (P < 0.001). Compared to patients without ADRs and those with mild/moderate ADRs, patients with severe ADRs exhibited significantly decreased RTL (P < 0.001, P < 0.001, respectively). ROC curve analysis uncovered a diagnostic value of RTL as a biomarker of Osimertinib-induced ADRs (AUC = 1.000, P < 0.001). Kaplan-Meier analysis revealed a significant association between shorter RTL and increased cumulative incidence of Osimertinib-induced ADRs in patients with advanced-stage NSCLC (P < 0.001). Shorter RTL in blood leukocytes would reflect the occurrence of Osimertinib-induced ADRs and might emerge as a promising biomarker for identifying advanced-stage NSCLC patients who are at risk of experiencing Osimertinib-induced ADRs, particularly those with severe ADRs. [ABSTRACT FROM AUTHOR]

Background: Telomere length is closely associated with the occurrence and development of cardiovascular and other diseases. Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel indicator of inflammation, oxidative stress, and metabolic syndrome, with some predictive ability for related disease risks in clinical practice. However, there is no research on the correlation between these two factors. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, we conducted analysis and research on the correlation between MHR and telomere length using the Kruskal-Wallis H test, Spearman rank correlation analysis, and partial correlation analysis. Weighted linear regression analysis assessed the strength of the association between the two variables, while restricted cubic spline regression (RCS) explored potential nonlinear relationships between them. Results: The results of correlation analysis showed that MHR levels were negatively correlated with telomere length (ρ=-0.083, P < 0.001), and this relationship remained statistically significant after controlling for other covariates (P all < 0.001). Weighted linear regression analysis showed that after adjusting for all covariates, MHR remained negatively associated with telomere length (β = -0.020; 95% CI: -0.039 to -0.002; P = 0.037). Subgroup analysis shows that the negative association between MHR and telomere length appeared more striking among females (훽 = -0.024; 95%CI: -0.050 to 0.001; P = 0.058), the Non-Hispanic White (훽 = -0.022; 95%CI: -0.045 to 0.002; P = 0.066), and other race (훽 = -0.067; 95%CI: -0.134 to -0.000; P = 0.049). Using RCS explored potential nonlinear relationships between MHR and telomere length, revealing no nonlinear relationship between the two (P = 0.102). Conclusions: This study suggests a negative correlation between MHR levels and telomere length in American adults. More comprehensive research is needed to confirm these findings in the future. [ABSTRACT FROM AUTHOR]

Climate warming poses a significant threat to species worldwide, particularly those inhabiting arid and semi‐arid regions where extreme temperatures are increasingly prevalent. However, empirical studies investigating how moderate heat events affect the physiological processes of arid and semi‐arid animals are largely scarce. To address this knowledge gap, we used an arid and semi‐arid lizard species (Phrynocephalus przewalskii) as a study system. We manipulated thermal environments to simulate moderate heat events (43.5 ± 0.3°C during the heating period) for lizards and examined physiological and biochemical traits related to survival, metabolism, locomotion, oxidative stress, and telomere length. We found that the body condition and survival of the lizards were not significantly affected by moderate heat events, despite an increase in body temperature and a decrease in locomotion at high test temperatures were detected. Mechanistically, we found that the lizards exhibited down‐regulated metabolic rates and enhanced activities of antioxidative enzymes, resulting in reduced oxidative damage and stable telomere length under moderate heat events. Based on these findings, which indicated a beneficial regulation of fitness by physiological and biochemical processes, we inferred that moderate heat events did not have a detrimental effect on the toad‐headed agama, P. przewalskii. Overall, our research contributes to understanding the impacts of moderate heat events on arid and semi‐arid species and highlights the adaptive responses and resilience exhibited by the toad‐headed agama in the face of climate warming. [ABSTRACT FROM AUTHOR]

Older parental age at birth is associated with increased risk of autism spectrum disorders (ASD) in offspring. Independently, shorter telomere length (TL) has also been shown to be associated with ASD in children. However, older paternal age at birth, with or without controlling for maternal age, has been associated with longer TL, a seemingly contradictory finding. Here, we conducted a retrospective cohort study among participants in the UK Biobank to disentangle associations between leukocyte TL and ASD status in adults, and the potential moderation by parental age on adult offspring's TL. Participants with ASD diagnosis (N = 87) with a mean age of 46.0 (SD 4.4) years were matched to participants without ASD diagnosis (N = 870) based on age, sex, ethnicity, education, household income, and assessment center. No statistically significant differences were seen in TL between participants with and without ASD when parental age at birth was not considered. However, there was a significant interaction between ASD diagnostic status and parental age on participants' TL, such that older paternal or maternal age at birth was more strongly associated with longer TL in participants with ASD. This study suggests that the shortened TL observed in children with ASD in previous research may partially depend on parental age at birth. Future studies tracking TL attrition before ASD diagnosis are warranted to depict temporal associations and the interacting effects of parental age at birth and ASD status on TL across the lifespan. Lay Summary: Older biological age, as measured by shortened telomere length, has been observed in children with autism spectrum disorders (ASD). In contrast, older parental age at birth has been related to both ASD risk and longer telomere length. In the present study, telomere length did not differ significantly between adults with and without ASD. However, we found that longer telomere length among adults with ASD versus adults without ASD could be more apparent in individuals with older parents. These findings suggest that parental age at birth may explain telomere length differences between individuals with and without ASD, and that the shorter telomere length previously found in children with ASD may depend on parental age at birth. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMethodsResultsConclusionsOur objective is to investigate the potential causal relationship between telomere length (TL) and aneurysmal subarachnoid hemorrhage (aSAH) and intracranial aneurysms (IAs) by conducting a bidirectional two-sample Mendelian Randomization (MR) study.We utilized publicly available summary data from genome-wide association studies (GWAS) for comprehensive analysis. Telomere length-associated data were sourced from the Epidemiology Unit (IEU) GWAS database (n = 472,174), while data pertaining to intracranial aneurysms were derived from a GWAS meta-analysis conducted by Bakker et al, encompassing aneurysmal subtypes including aSAH (n = 77,074), IAs (n = 79,429), and unruptured intracranial aneurysms (uIA) (n = 74,004), all sampled from European populations. The primary method for MR analysis employed was the Inverse Variance Weighted (IVW) method. Additionally, we conducted various sensitivity analyses to assess the heterogeneity and pleiotropy of study findings. Reverse MR analysis was employed to explore potential reverse causality.In the forward MR analysis, the IVW method indicated a negative association between TL and aSAH (OR = 0.636, 95% CI: 0.459–0.883, p = 0.006) as well as IAs (OR = 0.670, 95% CI: 0.499–0.900, p = 0.0079). There was no evidence of heterogeneity or horizontal pleiotropy in the forward MR analysis. Reverse MR analysis did not reveal any causal relationship between aSAH, IAs, uIA and TL.In European populations, there exists a causal relationship between longer TL and reduced risks of aSAH and IAs Further research is warranted to elucidate the underlying mechanisms and the potential of TL as an intervention target for lowering the incidence of aSAH and IAs. [ABSTRACT FROM AUTHOR]

Background: As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery. Methods: Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped. Results: TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls. Conclusions: The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL. [ABSTRACT FROM AUTHOR]

Background: This study aims to verify the relationship between screen and sleep time, body mass index (BMI) and immunological factors with telomere length according to leisure-time physical activity (PA) in children and adolescents. Methods: A cross-sectional study involving a sample of 476 schoolchildren of both sexes, aged seven to 17 years, from a community in southern Brazil. Behavioral variables (PA, sleep time, and screen time) were self-reported using a questionnaire. PA was classified as inactive and any PA (doing some physical activity). The associations of screen time, sleep time, BMI, and immunologic factors with telomere length were tested using multiple linear regression models, with the sample divided according to the schoolchildren's leisure-time physical activity practices. Results: An inverse association between BMI and telomere length (β: -0.239; 95% CI: -0.468; -0.010) and a direct association of leukocytes (β: 0.151; 95% CI: 0.029; 0.278) and neutrophils (β: 0.131; 95% CI: 0.008; 0.254) with telomeres were found in the inactive students. No association was found between screen time and sleep time and telomeres. No association was found among students who engaged in any PA. Conclusion: The associations between telomeres, BMI, and immunologic factors were found only in inactive students. These results suggest that the association between BMI and immunological factors and telomere length may be influenced by physical activity. [ABSTRACT FROM AUTHOR]

Background Cognitive decline, a common process of brain ageing, has been associated with telomere length (TL). Delving into the identification of reliable biomarkers of brain ageing is essential to prevent accelerated cognitive impairment. Methods We selected 317 non-smoking 'Prevención con Dieta Mediterránea-Plus' (PREDIMED-Plus) participants (mean age, 65.8 ± 5.0 years) with metabolic syndrome from two trial centres who were following a lifestyle intervention. We measured TL and cognitive function at baseline and after 3 and 4 years of follow-up, respectively. Associations between baseline or 3-year changes in TL and baseline or 4-year changes in cognitive function were analysed using multivariable regression models. Results Baseline TL was not associated with baseline cognitive performance. Nevertheless, longer baseline TL was associated with improved 4-year changes in the Executive Function domain (β: 0.29; 95%CI: 0.12 to 0.44; P < 0.001) and the Global Cognitive Function domain (β: 0.19; 95%CI: 0.05 to 0.34; P = 0.010). Besides, a positive association was found between longer baseline TL and improved 4-year changes in the animal version of the Verbal Fluency Test (β: 0.33; 95%CI: 0.12 to 0.52; P =  0.002). By contrast, 3-year changes in TL were not associated with changes in cognitive function after 4 years. Conclusions Longer baseline TL could protect from cognitive decline and be used as a useful biomarker of brain ageing function in an older Mediterranean population at risk of cardiovascular disease and cognitive impairment. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potential cure for myelodysplastic neoplasms (MDSs) and other hematologic malignancies. This study investigates post-transplantation genetic evolution and telomere dynamics in hematopoietic cells, with a focus on clonal hematopoiesis (CH). We conducted a longitudinal analysis of 21 MDS patients who underwent allo-HSCT between September 2009 and February 2015. Genetic profiles of hematopoietic cells from both recipients and donors were compared at equivalent pre- and post-transplantation time points. Targeted sequencing identified CH-associated mutations, and real-time quantitative PCR measured telomere length. Furthermore, we compared CH incidence between recipients and age-matched controls from the GENIE cohort from routine health checkups. Post-allo-HSCT, 38% of recipients developed somatic mutations not detected before transplantation, indicating de novo CH originating from donor cells. Compared to age-matched healthy controls, recipients showed a significantly higher incidence of CH, suggesting increased susceptibility to genetic changes post-transplant. Telomere length analysis also revealed accelerated shortening in transplanted cells, highlighting the heightened stress and proliferation demands in the new microenvironment. Our findings reveal a notable incidence of donor-derived CH in allo-HSCT recipients, alongside significant telomere attrition. This suggests the potential influence of the marrow microenvironment on genetic and molecular changes in hematopoietic cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer affects millions worldwide, with gastrointestinal cancers being notably common. This review explores the potential of telomeres and telomerase as biomarkers for diagnosing and predicting these cancers. Telomeres are protective caps at chromosome ends that shorten with cell division, while telomerase helps extend them. Changes in these markers could indicate cancer risk and progression. Despite efforts to prevent cancer through lifestyle changes, gastrointestinal cancers such as colorectal and gastric cancer remain prevalent. Current detection methods like endoscopy are invasive, driving interest in non-invasive alternatives. By consolidating research on telomere length and telomerase activity, this review aims to highlight how these biomarkers could enhance early diagnosis and monitoring. Understanding these mechanisms better could lead to improved diagnostic tools and therapeutic strategies, potentially refining how gastrointestinal cancers are managed and improving patient outcomes. Gastrointestinal (GI) cancers, such as colorectal and gastric cancers, pose significant global health challenges due to their high rates of incidence and mortality. Even with advancements in treatment and early detection, many patients still face poor outcomes, highlighting the critical need for new biomarkers and therapeutic targets. Telomere length (TL) and telomerase activity (TA) have gained attention in this context. Telomeres, protective nucleotide sequences at chromosome ends, shorten with each cell division, leading to cellular aging. Telomerase, a ribonucleoprotein enzyme, counteracts this shortening by adding telomeric repeats, a process tightly regulated in normal cells but often dysregulated in cancer. This review critically evaluates the role of TL and TA in the pathogenesis of GI cancers, examining their potential as diagnostic, prognostic, and predictive biomarkers. It explores how alterations in telomere biology contribute to the initiation and progression of GI tumors and assesses the therapeutic implications of targeting telomerase. By integrating findings from diverse studies, this review aims to elucidate the intricate relationship between telomere dynamics and gastrointestinal carcinogenesis, offering insights into how TL and TA could be leveraged to enhance the early detection, treatment, and prognosis of GI cancers. [ABSTRACT FROM AUTHOR]

The highly proliferative gut tissue exhibits rapid telomere shortening with systemic effects on the host organism. Recent studies have demonstrated a bidirectionality in interactions between intestinal telomere length dynamics and the composition and activity of the gut microbiome thus linking processes of inflammation, dysbiosis and aging across different vertebrate species. [ABSTRACT FROM AUTHOR]

Aim: To comprehensively examine the associations of childhood and adulthood body size, and child‐to‐adult body size change with adult leucocyte telomere length (LTL). Methods: We included 453 602 participants from the UK Biobank. Childhood body size at the age of 10 years was collected through a questionnaire. Adulthood body size was assessed using body mass index (BMI), waist circumference (WC), waist‐to‐hip ratio (WHR), fat mass index (FMI), and fat‐free mass index (FFMI). Results: Individuals with plumper body size in childhood exhibited shorter LTL in adulthood (−0.0086 [−0.0017, −0.0004]). Adulthood BMI (−0.0286 [−0.0315, −0.0258]), WC (−0.0271 [−0.0303, −0.0238]), WHR (−0.0269 [−0.0308, −0.0230]) and FMI (−0.0396 [−0.0438, −0.0351]) were negatively associated with LTL, whereas FFMI (0.0095 [0.0039, 0.0152]) was positively associated with LTL. Compared to individuals consistently having an average/normal weight in both childhood and adulthood, those who maintained or developed overweight/obesity from childhood to adulthood had a shorter adult LTL, regardless of childhood body size. Notably, the LTL shortening effect was not observed in individuals with plumper body size in childhood but normal weight in adulthood. Conclusions: Childhood and adulthood obesity are both associated with LTL shortening in adulthood. Transitioning to or maintaining overweight/obese status from childhood to adulthood is associated with shorter adult LTL, whereas this effect can be reversed if plumper children become normal weight. [ABSTRACT FROM AUTHOR]

This study employed a genome-wide association study (GWAS) to investigate the relationship between telomere length and marginal bone loss (MBL), a marker of bone health and aging. Telomere length, a biological indicator of aging, was analyzed alongside several serum markers of bone loss. Following a screen for appropriate instrumental variables, telomere length was designated as the exposure variable. We conducted the main analysis using random-effects inverse variance weighting (IVW) and supplemented it with MR Egger, weighted median, simple mode, and weighted mode analyses, employing a total of five methods. Positive outcomes underwent scrutiny through heterogeneity analysis, horizontal multiplicity analysis, and leave-one-out plot. Subsequently, the effective gene locus was chosen for a reverse MR analysis, with positive results serving as the exposure variable. We found a causal relationship between telomere length and the expression of osteocalcin (OC), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-12 (MMP-12), key markers of bone metabolism. Our findings suggest that telomere wear and shortening may contribute to increased activity of OC, MMP-3, and MMP-12, thus affecting bone metabolism. However, reverse Mendelian randomization analysis did not indicate a significant impact of OC, MMP-3, and MMP-12 on telomere length, implying a unidirectional relationship. Overall, this meta-analysis underscores the association between telomere length and bone loss, highlighting the importance of timing and duration of telomere wear and shortening in influencing bone metabolism. [ABSTRACT FROM AUTHOR]

Background: Benign prostatic hyperplasia (BPH) is a growing issue due to an ageing population. Our study investigated the possible associations between BPH and ageing hallmarks, including the telomere length (TL) and mitochondrial genome copy number (mtDNA CN), along with genetic variations in the TP53 gene and mtDNA. Methods: Prostate tissue samples were obtained from 32 patients with BPH, together with 30 blood samples. As a healthy control group, age-matching blood DNA samples were used. For the comparison of mtDNA sequence data, 50 DNA samples of the general Latvian population were used. The full mtDNA genome was analyzed by using Next-Generation Sequencing (NGS), the TP53 gene by Sanger sequencing, and the mtDNA copy number (mtDNA CN) and telomere length (TL) byqPCR assay. Results: The results showed that in BPH patients, telomeres in the prostate tissue were significantly longer than in blood cells, while the TL in blood cells of the healthy controls was the shortest. Also, the mtDNA amount in the prostate tissue of BPH patients was significantly greater in comparison with blood cells, and controls had the smallest mtDNA CN. We did not find any mutations in the TP53 gene that could be linked to BPH; however, in mtDNA, we found several unique mutations and heteroplasmic changes, as well as genetic changes that have been previously associated with prostate cancer. Conclusions: In conclusion, prolonged telomeres and changes in the mtDNA amount might be involved in the molecular mechanisms of BPH. Some of the heteroplasmic or homoplasmic mtDNA variants might also contribute to the development of BPH. Additional studies are needed to substantiate these findings. [ABSTRACT FROM AUTHOR]

Background/Objectives: Emerging evidence suggests that patients suffering from COVID-19 may experience neurocognitive symptoms. Furthermore, other studies indicate a probable association between leukocyte telomere length (LTL) and neurocognitive changes in subjects with post-COVID-19 condition. Our study was designed to determine the correlation between telomere length and cognitive changes in post-COVID-19 subjects. Methods: This study included 256 subjects, categorized based on SARS-CoV-2 infection from 2020 to 2023. In addition, subjects with a psychiatric diagnosis were considered. Moreover, the MoCA and MMSE scales were applied. Telomere length was determined using a polymerase chain reaction, and statistical analysis was employed using ANOVA and X2 tests. Results: We identified a decrease in LTL in individuals with post-COVID-19 conditions compared to those without SARS-CoV-2 infection (p ≤ 0.05). However, no association was found between LTL and cognitive impairment in the subjects post-COVID-19. Conclusions: The findings suggest that LTL is affected by SARS-CoV-2 infection. Nonetheless, this important finding requires further research by monitoring neurological changes in subjects with post-COVID condition. [ABSTRACT FROM AUTHOR]

The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is well recognized as a critical regulator of redox, metabolic, and protein homeostasis, as well as the regulation of inflammation. An age-associated decline in NRF2 activity may allow oxidative stress to remain unmitigated and affect key features associated with the aging phenotype, including telomere shortening. Telomeres, the protective caps of eukaryotic chromosomes, are highly susceptible to oxidative DNA damage, which can accelerate telomere shortening and, consequently, lead to premature senescence and genomic instability. In this review, we explore how the dysregulation of NRF2, coupled with an increase in oxidative stress, might be a major determinant of telomere shortening and age-related diseases. We discuss the relevance of the connection between NRF2 deficiency in aging and telomere attrition, emphasizing the importance of studying this functional link to enhance our understanding of aging pathologies. Finally, we present a number of compounds that possess the ability to restore NRF2 function, maintain a proper redox balance, and preserve telomere length during aging. [ABSTRACT FROM AUTHOR]

Iron is essential for organ system development, DNA replication, and metabolic processes. Excessive iron storage can lead to oxidative stress, which can cause age-related conditions. Telomere length is a biomarker for aggregate oxidative stress and biological ageing, linked to age-related diseases and ailments. High body iron status may cause oxidative stress, leading to the loss of telomeric sequences. However, no research has been conducted on the relationship between telomere length and iron profile in South Canara residents. Understanding this association can help devise protocols to recover neonatal outcomes. The aim of this study is to determine the relationship between iron profile status and telomere length in cord blood. 73 cord blood sample was collected at the time of birth from participants visiting the outpatient Department of Obstetrics and Gynaecology. Demographic, anthropometric information and baseline characteristics of the consented study participants was obtained. Iron profile status and Telomere length was assessed by standardised protocol. In this study, positive association was observed between serum ferritin and rTL, groups adjusted based on birth mode and diagnosis of hyperbilirubinemia also showed a positive association between rTL and ferritin, while negative association between rTL and serum iron in cord blood of neonates birthed through LSCS. In conclusion, this study found significant relationships between relative telomere length, telomerase activity and iron profile status in cord blood. In conclusion, compared to relative telomere length, Telomerase is strongly associated with iron profile in the cord blood. [ABSTRACT FROM AUTHOR]

Telomere length is a putative biomarker of aging and is associated with multiple age-related diseases. There are limited data on the landscape of rare genetic variations in telomere length. Here, we systematically characterize the rare variant associations with leukocyte telomere length (LTL) through exome-wide association study (ExWAS) among 390,231 individuals in the UK Biobank. We identified 18 robust rare-variant genes for LTL, most of which estimated effects on LTL were significant (> 0.2 standard deviation per allele). The biological functions of the rare-variant genes were associated with telomere maintenance and capping and several genes were specifically expressed in the testis. Three novel genes (ASXL1, CFAP58, and TET2) associated with LTL were identified. Phenotypic association analyses indicated significant associations of ASXL1 and TET2 with cancers, age-related diseases, blood assays, and cardiovascular traits. Survival analyses suggested that carriers of ASXL1 or TET2 variants were at increased risk for cancers; diseases of the circulatory, respiratory, and genitourinary systems; and all-cause and cause-specific deaths. The CFAP58 carriers were at elevated risk of deaths due to cancers. Collectively, the present whole exome sequencing study provides novel insights into the genetic landscape of LTL, identifying novel genes associated with LTL and their implications on human health and facilitating a better understanding of aging, thus pinpointing the genetic relevance of LTL with clonal hematopoiesis, biomedical traits, and health-related outcomes. [ABSTRACT FROM AUTHOR]

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 < 1.02T/S ratio. These findings suggest age influences the association between telomere length and migraine in U.S. adults. [ABSTRACT FROM AUTHOR]

Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein–protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies. [ABSTRACT FROM AUTHOR]

Introduction: Patients with chronic kidney disease, especially those with end-stage kidney disease (ESKD) on hemodialysis (HD), are at increased risk for cardiovascular disease (CVD), including myocardial infarction and ischemic stroke. A shortening in telomere length, as a parameter for accelerated vascular aging, is an established biomarker for CVD in the general population. We aimed to elucidate the role of telomere length in ESKD patient on HD and its association with cardiovascular outcomes. Methods: Telomere length was measured in a prospective population-based cohort study of prevalent HD patients. DNA was isolated from whole blood, sampled at baseline, and analyzed for telomere length via a qPCR-based approach. The risk for the occurrence of the independently adjudicated three-point major adverse cardiovascular event outcome (myocardial infarction, ischemic stroke, and cardiovascular death) was statistically analyzed considering the competing risk of non-cardiovascular death. Results: In the cohort of 308 patients with ESKD (115 [37.3%] women, median [25th–75th percentile] age: 67.0 [56.8–76.0]), the median telomere length was 1.51 kb (25th–75th percentile 0.6–3.2 kb). The 3P-MACE outcome occurred with an incidence rate of 9.4 per 100 patient-years. Patients with longer telomere length more frequently had vascular nephropathy compared to patients with shorter telomere length. Interestingly, patients in the highest quartile of telomere length had a 1.8-fold increased risk for 3P-MACE (95% CI: 1.051–3.201, p = 0.033), after multivariable adjustment for age, history of stroke, myocardial infarction, venous thromboembolism, presence of heart valve replacement, atrial fibrillation, smoking, anticoagulation, or immunosuppressive use. Conclusion: Surprisingly, in this high-risk cohort of patients with ESKD on HD, longer telomere lengths were associated with increased risk of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study is to investigate the causal effect and potential mechanisms between telomere length and abdominal aortic aneurysm (AAA). Methods: Summary statistics of telomere length and AAA were derived from IEU open genome-wide association studies and FinnGen R9, respectively. Bidirectional Mendelian randomization (MR) analysis was conducted to reveal the causal relationship between AAA and telomere length. Three transcriptome datasets were retrieved from the Gene Expression Omnibus database and telomere related genes was down-loaded from TelNet. The overlapping genes of AAA related differentially expressed genes (DEGs), module genes, and telomere related genes were used for further investigation. Telomere related diagnostic biomarkers of AAA were selected with machine learning algorisms and validated in datasets and murine AAA model. The correlation between biomarkers and immune infiltration landscape was established. Results: Telomere length was found to have a suggestive negative associations with AAA [IVW, OR 95%CI = 0.558 (0.317-0.701), P < 0.0001], while AAA showed no suggestive effect on telomere length [IVW, OR 95%CI = 0.997 (0.990-1.004), P = 0.4061]. A total of 40 genes was considered as telomere related DEGs of AAA. PLCH2, PRKCQ, and SMG1 were selected as biomarkers after multiple algorithms and validation. Immune infiltration analysis and single cell mRNA analysis revealed that PLCH2 and PRKCQ were mainly expressed on T cells, while SMG1 predominantly expressed on T cells, B cells, and monocytes. Murine AAA model experiments further validated the elevated expression of biomarkers. Conclusion: We found a suggestive effect of telomere length on AAA and revealed the potential biomarkers and immune mechanism of telomere length on AAA. This may shed new light for diagnosis and therapeutics on AAA [ABSTRACT FROM AUTHOR]

Summary: Severe aplastic anaemia (SAA) is a rare and life‐threatening bone marrow failure disorder. We used data from the transplant outcomes in aplastic anaemia study to characterize mosaic chromosomal alterations (mCAs) in the peripheral blood of 738 patients with acquired SAA and evaluate their associations with telomere length (TL) and survival post‐haematopoietic cell transplant (HCT). The median age at HCT was 20.4 years (range = 0.2–77.4). Patients with SAA had shorter TL than expected for their age (median TL percentile for age: 35.7th; range <1–99.99). mCAs were detected in 211 patients (28.6%), with chr6p copy‐neutral loss of heterozygosity (6p‐CNLOH) in 15.9% and chr7 loss in 3.0% of the patients; chrX loss was detected in 4.1% of female patients. Negative correlations between mCA cell fraction and measured TL (r = −0.14, p = 0.0002), and possibly genetically predicted TL (r = −0.07, p = 0.06) were noted. The post‐HCT 3‐year survival probability was low in patients with chr7 loss (39% vs. 72% in patients with chr6‐CNLOH, 60% in patients with other mCAs and 70% in patients with no mCAs; p‐log rank = 0.001). In multivariable analysis, short TL (p = 0.01), but not chr7 loss (p = 0.29), was associated with worse post‐HCT survival. TL may guide clinical decisions in patients with SAA. [ABSTRACT FROM AUTHOR]

Telomeres, the protective chromosomal ends, progressively shorten and potentially are implicated in the pathogenesis of age-related diseases. In type 2 diabetes (T2DM), telomere shortening may play an important role, but the whole 'picture' remains limited. From a therapeutic perspective, the phytonutrient quercetin appears to be clinically effective and safe for patients with T2DM. Considering the above, we aimed to examine whether quercetin could interfere with telomere length (TL) dynamics. One hundred patients with T2DM on non-insulin medications registered within a primary healthcare facility were stratified by age and sex and randomly assigned to either standard care or standard care plus quercetin (500 mg/day) for 12 weeks, succeeded by an 8-week washout period and another 12 weeks of supplementation. Of the 88 patients completing the trial, 82 consented to blood sampling for TL measurements. Health assessments and whole blood absolute TL measurements using quantitative polymerase chain reaction (qPCR) were conducted at baseline and study end, and the findings of this subcohort are presented. Quercetin supplementation was associated with a significant increase in mean TL (odds ratio ≥ 2.44; p < 0.05) with a strengthened association after full adjustment for potential confounders through multiple logistic regression analysis (odds ratio = 3.48; p = 0.026), suggesting it as a potentially promising supplementation option. Further studies are needed to confirm this finding, elucidating the underlying molecular mechanisms of quercetin. [ABSTRACT FROM AUTHOR]

Background: Leukocyte telomere length (LTL) shortens with age and may be related to multiple sclerosis (MS). Objective: We hypothesize that chronologically young people with MS (pwMS) with short LTL behave similarly to older MS subjects. Methods: Prospective 2-year study including two cohorts of young (18–35 years) and elderly (⩾50 years) pwMS with similar disease duration. Physical and cognitive evaluation, 3 T brain magnetic resonance imaging (MRI) and retinal nerve fiber layer (RNFL) measurement by optical coherence tomography were performed. LTL was measured by quantitative polymerase chain reaction assay. Results: Around 105 patients were included, 57 young and 48 elderly. LTL was shorter in older patients (0.61 versus 0.57, p = 0.0081) and in males (female, 0.60; male, 0.59; p = 0.01335). For every 10-year increase in age, LTL was 0.02 U shorter. In elderly, LTL correlated with disease duration (p = 0.05), smoking (p = 0.03), Expanded Disability Status Scale (EDSS; p = 0.004), 9HPT (p = 0.00007), high-efficacy therapies (p = 0.001), brain lesion volume (BLV) (p = 0.011), and number of T2 lesions (p = 0.01). In young patients, LTL did not correlate with clinical or radiological variables. For every 0.1 U shorter LTL, gray matter volume decreased 1.75 cm3 and white matter volume 1.78 cm3. Conclusion: LTL correlated with disability and BLV in elderly. Besides LTL shortening, other variables should be considered as mechanisms of neurodegeneration that might be involved in aging pwMS. [ABSTRACT FROM AUTHOR]

Aging is an exceptionally complex process that depends on genetic, environmental, and lifestyle factors. Previous studies within the International HLA and Immunogenetics Workshop (IHIWS) component "Immunogenetics of Ageing" showed that longevity is associated with positive selection of HLA-DRB1*11- and DRB1*16-associated haplotypes, shown to be protective against diseases. Within the 18th IHIWS, we aimed to investigate the relevance of telomere length for successful aging and its association with classical HLAs. In total 957 individuals from Bulgaria, Turkey, Romania, and Poland in two age groups, elderly individuals (age 65–99 years) and ethnically matched young group (age 18–64 years), were investigated. The obtained results confirmed interpopulation differences in the distribution of HLA alleles, documented the lengths of telomeres in analyzed populations, and demonstrated significant associations of telomere length with aging as well as with the presence of some HLA class I or class II alleles. They suggest that telomere length assessment combined with HLA genotyping may help identify immunogenetic profiles associated with longevity. The associations between HLA and telomeres support the theory that HLA genes influence the aging process. However, further research is needed to clarify the biological basis of the observed relationships. [ABSTRACT FROM AUTHOR]

Selenoprotein P (SELENOP) transports selenium to extrahepatic tissues and is a biomarker of selenium status. Low soil selenium leads to low dietary selenium intake. A consequence is an increased risk of cardiovascular disease. To investigate clinical aspects associated with SELENOP deficiency, including biomarkers of inflammation, quality of life, and mortality within 12 years, and the effect of dietary selenium and coenzyme Q 10 supplementation on SELENOP. SELENOP was determined at inclusion and after four years of supplementation in 403 elderly community-living participants low in selenium receiving selenium yeast (200 μg/day) and coenzyme Q 10 (200 mg/day), or placebo. Pre-intervention, the average serum selenium level was 67 μg/L. T-tests, repeated measures of variance, Cox proportional regressions analyses, Kaplan-Meier graphs and ANCOVA analyses were applied. Associations with biomarkers of inflammation, telomere length, quality of life and mortality were investigated. Benchmark modelling was used to determine the serum selenium concentration at which the saturation levels of SELENOP and GPx3 was achieved. Comparison with GPx3 and serum selenium to identify increased mortality risk was performed, and the effect of supplementation on SELENOP levels were evaluated. Inverse associations were observed between the level of SELENOP at inclusion and biomarkers for inflammation. At follow-up, shorter telomere lengths were seen in those with low levels of SELENOP at inclusion, whereas high levels of SELENOP were associated with better quality of life and decreased mortality. SELENOP had increased prognostic power compared to GPx3 and selenium. Saturation of SELENOP was achieved at a serum selenium level of 146 μg/L, and for GPx3 at 99 μg/L. Supplementation induced higher levels of SELENOP. Significant associations between SELENOP and inflammation, length of telomeres, quality of life, and mortality were observed. Thus, selenium supplementation improved SELENOP expression, thereby facilitating systemic selenium bioavailability and resulting in the observed positive health effects. [Display omitted] • Low and decreasing selenoprotein P (SELENOP) status in elderly subjects associated with all-cause and cardiovascular mortality. • Low SELENOP was associated with increased telomere attrition and impaired quality of life. • Randomized controlled intervention with selenium and coenzymeQ10 raised serum SELENOP. • Increased SELENOP associated with reduced telomere attrition, mortality, and improved quality of life. • SELENOP may translate the applied supplements into improved selenium transport, status and health benefits. [ABSTRACT FROM AUTHOR]

MiRNAs, a class of non-coding RNA molecules, have emerged as critical modulators of telomere length and telomerase activity by finely tuning the expression of target genes (and not gene targets) within signaling pathways involved in telomere homeostasis. The primary objective of this systematic review was to compile and synthesize the existing body of knowledge on the role, association, and involvement of miRNAs in telomere length. Additionally, the review explored the regulation, function, and activation mechanism of the human telomerase reverse transcriptase (hTERT) gene and telomerase activity in tumor cells. A comprehensive analysis of 47 selected articles revealed 40 distinct miRNAs involved in these processes. These miRNAs were shown to exert their function, in both clinical cases and cell line models, either directly or indirectly, regulating hTERT and telomerase activity through distinct molecular mechanisms. The regulatory roles of these miRNAs significantly affected major cancer phenotypes, with outcomes largely dependent on the tissue type and the cellular actions within the tumor cells, whereby they functioned as oncogenes or tumor suppressors. These findings strongly support the pivotal role of miRNAs in modulating telomere length and telomerase activity, thereby contributing to the intricate and complex regulation of telomere homeostasis in tumor cells. Moreover, they emphasize the potential of targeting miRNAs and key regulatory genes as therapeutic strategies to disrupt cancer cell growth and promote senescence, offering promising avenues for novel cancer treatments. Mechanisms of action of miRNAs in regulating the hTERT complex and their impact on the tumor cells phenotypes. [ABSTRACT FROM AUTHOR]

Leukocyte telomere length (LTL) is an objective biomarker of biological aging, and it is proposed to play a crucial role in Alzheimer's disease (AD) risk. We aimed at evaluating the cross-sectional association between LTL and cognitive performance in middle-aged cognitively unimpaired individuals at increased risk of AD. A total of 1520 participants from the ALFA cohort were included. Relative telomere length was measured in leukocytes through qPCR. LTL was residualized against age and sex, and associations with cognitive performance were assessed in short and long groups based on residualized LTL (rLTL). Interactions with sex and genetic risk of AD were tested. Non-linear associations were found between LTL and episodic memory (EM). Better EM was associated with longer rLTL among women in the short rLTL group. Results suggest a potential role of telomeres in the cognitive aging process with sex-specific patterns. • There is a non-linear association between telomere length and cognitive performance. • Longer telomeres are associated with higher episodic memory scores. • The association between telomeres and cognitive performance might be sex-specific. [ABSTRACT FROM AUTHOR]

Telomeres are ribonucleoprotein structures that form a protective buffer at the ends of chromosomes, maintaining genomic integrity during the cell cycle. A decrease in average telomere length is associated with with age and with aging-related diseases such as cancer and cardiovascular disease. In this study, we conducted a randomized, double-blind, placebo-controlled trial over six months to compare the effects of the Astragalus-based supplement versus a placebo on telomere length (TL) in 40 healthy volunteers (mean age 56.1 ± 6.0 years). Twenty subjects received the supplement, and 20 received placebo capsules. All participants completed the study, and no adverse side effects were reported at six months. Subjects taking the Astragalus-based supplement exhibited significantly longer median TL (p = 0.01) and short TL (p = 0.004), along with a lower percentage of short telomeres, over the six-month period, while the placebo group showed no change in TL. This trial confirmed that the supplement significantly lengthens both median and short telomeres by increasing telomerase activity and reducing the percentage of short telomeres (<3 Kbp) in a statistically and possibly clinically significant manner. These results align with a previous open prospective trial, which found no toxicity associated with the supplement's intake. These findings suggest that this Astragalus-based supplement warrants further investigation for its potential benefits in promoting health, extending life expectancy, and supporting healthy aging. [ABSTRACT FROM AUTHOR]

Background: We explore the association between leucocyte telomere length (LTL) and all-cause and cardiovascular disease (CVD)-specific death in CVD patients. Methods: We acquired 1599 CVD patients from a nationally representative US population survey for this study. We applied Kaplan–Meier curves, adjusted weighted Cox regression models, and restricted cubic spline to investigate the association between LTL and all-cause death. Additionally, we employed competing risk regression to assess the impact of LTL on cardiovascular-specific death, setting non-cardiovascular death as a competing event. Results: The overall mortality rate was 31.0% after a median follow-up of 13.9 years. Patients with shorter LTL exhibited a higher risk of all-cause death, with an adjusted hazard ratio (HR) of 1.25 (95% confidence interval (CI): 1.05–1.48). Restricted cubic spline illustrated a linear dose-response relationship. In gender-specific analyses, female patients with shorter LTL showed a higher risk of death (weighted HR, 1.79; 95% CI, 1.29–2.48), whereas this association was not observed in males (weighted HR, 0.90; 95% CI, 0.61–1.32). The Fine–Gray competing risk model revealed no significant relationship between LTL and cardiovascular-specific mortality but a significant association with non-cardiovascular death (adjusted HR, 1.24; 95% CI, 1.02–1.51). Conclusions: LTL is inversely associated with all-cause death in female CVD patients. The significant correlation between reduced LTL and increased all-cause mortality emphasizes LTL as a potential marker for tertiary prevention against cardiovascular disease. [ABSTRACT FROM AUTHOR]

Abstract Background Telomere length is closely associated with the occurrence and development of cardiovascular and other diseases. Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel indicator of inflammation, oxidative stress, and metabolic syndrome, with some predictive ability for related disease risks in clinical practice. However, there is no research on the correlation between these two factors. Methods Using data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002, we conducted analysis and research on the correlation between MHR and telomere length using the Kruskal-Wallis H test, Spearman rank correlation analysis, and partial correlation analysis. Weighted linear regression analysis assessed the strength of the association between the two variables, while restricted cubic spline regression (RCS) explored potential nonlinear relationships between them. Results The results of correlation analysis showed that MHR levels were negatively correlated with telomere length (ρ=-0.083, P

Abstract This study aimed to measure relative telomere length (RTL) in blood leukocytes of advanced-stage NSCLC patients either with or without Osimertinib-induced ADRs and determine whether RTL could serve as a biomarker of Osimertinib-induced ADRs. Blood leukocytes RTL were measured in 63 advanced-stage NSCLC patients and 62 age-matched healthy controls using real-time polymerase chain reaction. In patients with advanced-stage NSCLC, RTL was significantly shorter than that in healthy controls (P

Abstract It is known that telomere length (TL) (evaluated with T/S ratio) is shortened in the presence of obesity. In this study, we aimed to investigate how obesity in adolescents and non-alcoholic liver disease (NAFLD) within the obese group affect TL and the clinical significance of the human telomerase reverse transcriptase (hTERT) gene MNS16A VNTR variant in terms of NAFLD. Adolescents with exogenous obesity and healthy controls (aged 10–19 years) who applied to our adolescent outpatient clinic between May-October 2023 were included in this study. We performed upper abdominal ultrasonography to investigate the presence of NAFLD in adolescents with obesity and divided into two groups: those without hepatosteatosis (obese NAFLD (-)) and those with hepatosteatosis (obese NAFLD (+)). We recorded body weight, height, waist circumference, and blood pressure measurements and measured the T/S ratio (telomere sequence copy number/gene single copy number) by the Quantitative Polymerase Chain Reaction method. The groups were compared using frequentist and Bayesian methods. Eighty-three obese adolescents [63 NAFLD(+) 20 NAFLD(-)] and 69 lean controls were included in the study. Pairwise comparisons revealed that T/S ratio was significantly lower in the obese NAFLD (-) group than the obese NAFLD (+) and the control group (p = 0.025, p = 0.007, respectively). T/S ratio was lower in the LL allele group than in the other alleles (p = 0.022) and slightly higher in the obese group with metabolic syndrome compared to the obese group without metabolic syndrome (p = 0.072). hTERT-MNS16A-VNTR gene variant LL allele had a negative correlation with T/S ratio among the obese adolescent group. Patients with LL alleles had higher ALT, GGT, HOMA-IR, and ALT/AST. Diastolic blood pressure had a significant correlation with the T/S ratio. The T/S ratio was shorter in the obese adolescent group compared to healthy ones but was higher in the NAFLD (+) obese compared to the NAFLD (-) obese. ALT level and ALT/AST ratio were higher, T/S ratio was lower in the hTERT MNS16A VNTR variant LL allele group among obese adolescents. In addition, there was a significant correlation between the T/S ratio and diastolic blood pressure in obese adolescents.

Abstract Background As a biological marker for cellular senescence, telomere length (TL) has been linked to a variety of psychiatric disorders and adverse childhood experiences (ACE), though only preliminarily to peripartum depression (PPD). The present study sought to examine the association between TL and PPD, assessing the moderating role of ACE and genetic polymorphic variations related with the telomere machinery. Methods Adversity was self-reported, likewise were depressive symptoms evaluated at pregnancy week 17 and 32, as well as six-weeks and six-months postpartum. TL was assessed by use of qPCR in blood samples collected during delivery from females with antenatal depression resolving postpartum, females with depression persisting to postpartum, and healthy controls. Twenty haplotype-tagging Single Nucleotide Polymorphisms in the Telomerase Reverse Transcriptase (TERT) and three in the Telomerase RNA Component (TERC) genes were genotyped. Results TL was negatively correlated with severity of PPD symptoms at pregnancy week 32 and postpartum week 6. PPD was associated with shorter TL. Lastly, ACE, but not the TERT/TERC genotype, moderated the TL-trajectory association; with increasing ACE, individuals with persistent PPD symptoms had shorter TL, whereas the opposite pattern (longer TL) was observed in the controls. Conclusions The findings contribute to further understanding of PPD underpinnings, suggesting a negative relationship with TL.

Abstract Background This study aims to verify the relationship between screen and sleep time, body mass index (BMI) and immunological factors with telomere length according to leisure-time physical activity (PA) in children and adolescents. Methods A cross-sectional study involving a sample of 476 schoolchildren of both sexes, aged seven to 17 years, from a community in southern Brazil. Behavioral variables (PA, sleep time, and screen time) were self-reported using a questionnaire. PA was classified as inactive and any PA (doing some physical activity). The associations of screen time, sleep time, BMI, and immunologic factors with telomere length were tested using multiple linear regression models, with the sample divided according to the schoolchildren’s leisure-time physical activity practices. Results An inverse association between BMI and telomere length (β: -0.239; 95% CI: -0.468; -0.010) and a direct association of leukocytes (β: 0.151; 95% CI: 0.029; 0.278) and neutrophils (β: 0.131; 95% CI: 0.008; 0.254) with telomeres were found in the inactive students. No association was found between screen time and sleep time and telomeres. No association was found among students who engaged in any PA. Conclusion The associations between telomeres, BMI, and immunologic factors were found only in inactive students. These results suggest that the association between BMI and immunological factors and telomere length may be influenced by physical activity.

Background. Acquired aplastic anemia (AA) is a non-tumor disease of the blood system and the pathogenesis is based on immune dysregulation directed against own hematopoietic stem cells, which leads to the development of bone marrow aplasia. Some modern research is directed to the study of intrinsic defects of hematopoietic stem cells, and one of which is the change in telomere length. Several large studies have shown the association of telomere shortening in AA patients with decreased overall survival, poor response to immunosuppressive therapy (IST), high rates of relapse and clonal complications.Aim. To study the influence of the initial telomeric DNA regions length in AA patients on the disease course.Materials and methods. 43 adult patients with acquired AA without previous pathogenetic therapy were included in the study. IST was performed according to a standard protocol including the use of hATG and cyclosporine. Flow-FISH was used as the method for measuring relative telomere length, and peripheral blood mononuclear cells were used as the study material.Results. Telomere length determined before IST did not differ between non-severe and severe AA, but there were significant differences depending on disease duration (p = 0.032). Initially short telomeres correlated with a lower rate of achieving hematologic improvement (53 % vs. 80 %; p = 0.059). In addition, significantly worse results were obtained in achieving partial and complete remission in patients with initially short telomeres compared to those with initially long telomeres (37 % vs. 62 % and 5 % vs. 23 %, respectively; p

Abstract Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein–protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies.

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

BACKGROUND: Multiple observational studies have suggested a potential association between telomere length and musculoskeletal diseases. However, the underlying mechanisms remain unclear. OBJECTIVE: To investigate the genetic causal relationship between telomere length and musculoskeletal diseases using two-sample Mendelian randomization analysis. METHODS: Genome-wide association study summary data of telomere length were obtained from the UK Biobank. Genome-wide association study summary data of 10 common musculoskeletal diseases (osteonecrosis, osteomyelitis, osteoporosis, rheumatoid arthritis, low back pain, spinal stenosis, gout, scapulohumeral periarthritis, ankylosing spondylitis and deep venous thrombosis of lower limbs) were obtained from the FinnGen consortium. Inverse variance weighting, Mendelian randomization-Egger and weighted median methods were used to evaluate the causal relationship between telomere length and 10 musculoskeletal diseases. Inverse variance weighting was the primary Mendelian randomization analysis method, and sensitivity analysis was performed to explore the robustness of the results. RESULTS AND CONCLUSION: (1) Inverse variance-weighted results indicated a negative causal relationship between genetically predicted telomere length and rheumatoid arthritis (odds ratio=0.78, 95% confidence interval: 0.64-0.95, P=0.015) and osteonecrosis (odds ratio=0.56, 95% confidence interval: 0.36-0.90, P=0.016). No causal relationship was found between telomere length and the other eight musculoskeletal diseases (all P > 0.05). (2) Sensitivity analysis affirmed the robustness of these causal relationships, and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy (all P > 0.05). (3) This Mendelian randomized study supports that telomere length has protective effects against rheumatoid arthritis and osteonecrosis. However, more basic and clinical research will be needed to support our findings in the future. [ABSTRACT FROM AUTHOR]

Objective: To explore the relationship between YKL-40 level, telomere length, and different subtypes of insomnia disorder. Methods: A total of 145 individuals suffering from insomnia were enrolled and divided into four groups according to the insomniac subtypes: difficulty initiating sleep, early morning awakening, difficulty maintaining sleep, and mixed symptoms. Eighty healthy controls were also collected at the same time. Peripheral leukocyte genomic DNA was extracted, relative telomere lengths were measured using the real-time quantitative polymerase chain reaction method, and YKL-40 levels were determined using enzyme-linked immunoassay. Logistic regression modeling was used to analyze the correlation between different insomnia subtypes, YKL-40 level, and telomere length. Results: People with telomere lengths in the lowest tertile were more likely to have trouble falling asleep (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.22-3.63; p = 0.03) and had a higher frequency of mixed symptoms (OR 1.49, 95% CI 1.30-2.81; p = 0.04). People in the highest tertile of YKL-40 level had an increased chance of waking up early (OR 2.98, 95% CI 1.54-5.33; p = 0.01) and more mixed symptoms (OR 1.47, 95% CI 1.22-2.79; p = 0.02). Furthermore, using receiver operating characteristic curve analysis, the area under the curve of YKL-40 level and telomere length was 0.806 and 0.746, respectively. Conclusions: Telomere length in patients with difficulty initiating sleep and mixed symptoms was significantly shortened and the level of YKL-40 in people who have early morning awakening and mixed symptoms was significantly increased. Our findings provide the first evidence that leukocyte telomere length and YKL-40 level are individually linked to mixed symptoms. [ABSTRACT FROM AUTHOR]

Telomere length, a biomarker of human aging, is related to adverse health outcomes. Growing evidence indicates that oxidative stress and inflammation contributes to telomere shortening, whereas social support may protect from telomere shortening. Despite sex differences in telomere length and social support, little is known about whether there are sex differences in the relationship between oxidative stress/inflammation and telomere length, and sex-specific moderating roles of social support in older adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999–2002, this study assessed whether the associations between oxidative stress/inflammation and telomere length vary with sex and explored social support as a moderator in these associations among 2289 older adults. Oxidative stress was measured based on serum Gamma-glutamyl transferase (GGT), and inflammation was measured based on C-reactive protein (CRP). After adjusting for the covariates, GGT was significantly associated with telomere length in females only (β = − 0.037, 95% CI = − 0.070, − 0.005), while CRP was associated with telomere length in males only (β = − 0.019, 95% CI = − 0.035, − 0.002). Moreover, high social support mitigated the negative association between GGT and telomere length, which was more evident in females. Furthermore, social support moderated the association between CRP and telomere length in males aged 70 and above. Our findings indicated that biological mechanisms related to telomere length may vary with sex, while social support plays a sex-specific moderating role. [ABSTRACT FROM AUTHOR]

Purpose of Review: Telomere biology disorders (TBD) are a group of genetic disorders characterized by premature shortening of telomeres, resulting in accelerated aging of somatic cells. This often leads to major multisystem organ dysfunction, and TBDs have become increasingly recognized as a significant contributor to numerous disease processes within the past 10–15 years. Both research and clinical practice in this field are rapidly evolving. Recent Findings: A subset of patients with TBD suffers from interstitial lung disease, most commonly pulmonary fibrosis. Often, the clinical presentation is indistinguishable from other forms of lung fibrosis. There are no pathognomonic radiographic or histological features, and a high level of suspicion is therefore required. Telomere evaluation is thus crucial to establishing the diagnosis. Summary: This review details the clinical presentation, objective evaluation, indicated genetic testing, and recommended management strategies for patients affected by interstitial lung disease associated with TBDs. Our goal is to empower pulmonologists and other healthcare professionals who care for these patients to provide appropriate and personalized care for this population. [ABSTRACT FROM AUTHOR]

Abstract Background Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks. Methods This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran's Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR). Results Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P

Abstract Background Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. Methods Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. Results Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P