Circulating markers of biological aging associated with obstructive sleep apnea or insomnia in adults: A systematic review and meta-analysis.

To assess the potential utility of leukocytes and spermatozoa telomere length (LTL and STL) as reproductive biomarkers, this study measured both LTL and STL and investigated their possible correlations with oxidative status and semen quality parameters in healthy breeding male dogs. Twenty-two ejaculates and blood samples were collected from dogs of various breeds. Semen was evaluated for volume, concentration, sperm motility, and kinetic parameters using a Sperm Class Analyzer. LTL and STL were quantified using Quantitative PCR (qPCR) and expressed as the relative ratio of telomere repeat copy number (T) to a single-copy gene (S), T/S ratio. Serum oxidative stress markers were assessed using d-ROMs and Biological Antioxidant Potential (BAP) tests. Correlations between STL and LTL, as well as their association with age, semen parameters and oxidative stress levels, were evaluated using Spearman analysis. LTL and STL were 0.63±0.25 and 0.85±0.31 and showed a strong positive correlation (P<0.001; rs=0.70). Both LTL and STL were also negatively correlated with age (P<0.05 and rs=-0.50; P<0.001 and rs=-0.68). The cut-off age for the difference in STL and LTL was identified at 6 and 7.5 years, respectively. STL was also positively correlated with semen volume (P<0.05; rs=0.63) and concentration (P<0.05; rs=0.41) and negatively correlated with semen chromatin decondensation (P<0.01; rs=-0.71); while the LTL showed a positive correlation with sperm concentration (P<0.05; rs=0.53). No correlations with oxidative markers were found. These findings support the potential use of TL as a biomarker for reproductive aging and semen quality in dogs.

Sleep traits have been linked to aging, but observational designs cannot separate correlated sleep behaviors or establish causality. We used Mendelian randomization (MR) to estimate both total and direct effects of chronotype, daytime napping, and sleep duration on multidimensional aging outcomes. Two-sample MR used large GWAS instruments for the three sleep traits against leukocyte telomere length, facial ageing, epigenetic clocks (IEAA, HannumAge, PhenoAge, GrimAge), frailty index, and cognitive performance. Inverse-variance weighted (IVW) was primary, with MR-Egger, weighted median, and MR-PRESSO as sensitivity analyses. Univariable MR (UVMR) estimated total effects; multivariable MR (MVMR) estimated direct effects accounting for intercorrelations. In UVMR, napping was adversely associated with telomere length (β = -0.11, 95% CI - 0.18 to - 0.05, PFDR = 0.002), facial ageing (β = 0.05, 0.01-0.09, PFDR = 0.036), GrimAge (β = 0.96, 0.09-1.83, PFDR = 0.048), frailty (β = 0.32, 0.20-0.45, PFDR < 0.001), and cognition (β = -0.16, - 0.29 to - 0.03, PFDR = 0.036); HannumAge was nominal (β = 0.53, - 0.29-1.35, PFDR = 0.275). Chronotype related to HannumAge (β = 0.46, 0.15-0.78, PFDR = 0.032) with borderline links to IEAA (β = 0.36, 0.07-0.66, PFDR = 0.060) and poorer cognition (β = - 0.04, - 0.08 to - 0.01, PFDR = 0.060). Sleep duration was inversely associated with frailty (β = -0.17, - 0.26 to - 0.08, PFDR = 0.001). In MVMR, napping retained associations with GrimAge (β = 1.08, 0.02-2.15, P = 0.046) and frailty (β = 0.29, 0.15-0.43, P < 0.001), while links to telomere length and cognition attenuated. Chronotype became protective for facial ageing (β = -0.03, - 0.05 to - 0.01, P = 0.011) and cognition (β = 0.09, 0.01-0.17, P = 0.036) and showed no independent association with epigenetic clocks. The inverse association between sleep duration and frailty strengthened (β = -0.36, - 0.49 to - 0.22, P < 0.001). Sleep traits show distinct, partly independent causal links with aging: excessive napping adversely influences GrimAge and frailty; longer sleep duration independently protects against frailty; and chronotype benefits facial ageing and cognition after accounting for other sleep behaviors.

While literature suggests women with diminished ovarian reserve may have increased metabolic risk, implications for long-term health are unknown. To investigate the relationship between ovarian reserve markers at baseline with a subsequent measure of endothelial dysfunction, as a proxy for cardiovascular risk. Prospective cohort study. Community-based setting. 322 subjects from the Ovarian Aging Study (OVA), an NIH-funded study of ovarian aging (average 35.4 years old at the time of baseline ovarian reserve measurements, and 45.1 years old at the time of endothelial dysfunction measurement). This study investigated the association of ovarian reserve markers at baseline with a subsequent (average of 9.7 years) assessment of cardiovascular risk using the EndoPAT reactive hyperemia index (RHI) score of endothelial function. Secondary outcomes including the American Heart Association PREVENT score, metabolic syndrome, telomere length, and mitochondrial DNA were evaluated. RHI as a continuous outcome was significantly positively associated with both anti-Müllerian hormone (AMH) and antral follicle count (AFC) on fully adjusted models (AMH Coeff 0.052 95% CI 0.008 to 0.096, p = 0.02; AFC Coeff 0.017, 95% CI 0.001 to 0.032, p = 0.04). For secondary outcomes, the only result that was significant was the association of fully adjusted AFC with metabolic syndrome (OR 0.92, 95% CI 0.86-0.99, p = 0.02). A sensitivity analysis of the premenopausal cohort (N = 246) had similar findings. In this longitudinal cohort of women with normal ovarian aging, baseline ovarian reserve markers of AMH and AFC were positively associated with endothelial function as a continuous outcome. Baseline ovarian reserve markers were not related to most secondary outcomes of cellular aging and metabolic risk.

Informal e-waste recycling releases complex mixtures of hazardous substances, including heavy metals that bioaccumulate in exposed populations-especially among e-waste workers. Emerging evidence links these metals to telomere shortening, a key marker of cellular aging and DNA damage which can lead to noncommunicable diseases (NCDs). This study therefore examined the effects of metal exposure on telomere length among e-waste workers in Agbogbloshie compared to non-e-waste workers in Madina. A total of 78 samples (53 e-waste workers and 25 controls), each with three repeated measurements, were selected from the GEOHealth II study and analyzed for telomere length using quantitativepolymerase chain reaction (qPCR)technique. Restricted cubic spline (RCS) modeling was employed to assess the association between metal exposure and telomere length. This study observed consistently shorter relative telomere length among the e-waste workers, particularly those involved in burning activities. Lead (Pb) and chromium (Cr) levels were negatively associated with relative telomere length and zinc (Zn) showed a positive association while magnesium (Mg) exhibited a nonlinear relationship with telomere length. The consistently shorter relative telomere length among e-waste workers coinciding with higher concentrations of Cr and Pb implicates the role of metals in telomere shortening. Larger, long-term studies are recommended for future studies.

Evolutionary theory predicts that variation in longevity persists due to trade-offs between early-life fitness traits (e.g., growth or fecundity) and long-term somatic maintenance. However, such trade-offs can be difficult to detect and may often become apparent only under certain conditions. For instance, developing in novel or atypical environments may alter the genetic architecture of traits, revealing trade-offs that are otherwise hidden under normal conditions. To test this, we compared full-sibling families of the Mexican spadefoot (Spea multiplicata) reared across two larval diets: a typical detritus diet and an atypical live shrimp diet, which they are competitively excluded from in nature. The shrimp diet significantly increased broad-sense genetic variance and heritability for larval growth rate, whereas heritability for post-metamorphic telomere length - a known longevity correlate - remained similar across diets. Moreover, only on the shrimp diet did families with faster growth exhibit shorter telomeres, consistent with a diet-dependent trade-off between growth and somatic maintenance. Overall, our study shows that developing under atypical dietary conditions exposes previously cryptic genetic variation in growth, thereby revealing a trade-off with somatic maintenance. These findings have implications for understanding how environmental change, such as rapid dietary shifts, can shape aging processes and vulnerability to age-related disease.

The emerging influences of telomere and telomerase in inflammatory bowel disease and cancer progression.

Telomeres safeguard the genome, acting as sentinels of oxidative stress and preventing chromosome ends from eliciting a DNA damage response. PROTECTION OF TELOMERES 1 (POT1) is a highly conserved telomere protein, essential for chromosome integrity and telomeric DNA replication. Arabidopsis thaliana encodes two divergent POT1 paralogs: AtPOT1a stimulates telomerase activity, but AtPOT1b function is unknown. Here we show that AtPOT1b modulates reactive oxygen species (ROS) homeostasis. Oxidative stress induces AtPOT1b expression and telomeric accumulation, while AtPOT1b inactivation elevates ROS, increases telomeric and genome-wide oxidation, and causes stochastic telomere length changes. To address how AtPOT1b controls ROS, we report its localization in nuclei and peroxisomes, and association with catalases and peroxidases that enhance ROS scavenging. Impairing AtPOT1b-CAT2 interaction increases ROS accumulation and telomeric oxidation. Moss or human POT1 rescues ROS overaccumulation in Arabidopsis pot1b mutants, but not telomere deficiency in pot1a pot1b mutants, supporting a conserved role for POT1 in modulating ROS homeostasis and genome stability, distinct from canonical telomeric functions.

ABSTRACTIn species with parental care, the transition from dependence to independence is a critical stage during which juveniles must make key decisions for their future life. In colonial birds, the physiological state of juveniles during this transition may influence the timing of colony departure and subsequent movement patterns. Telomere length and DNA damage have been proposed as important biomarkers of early‐life stress and physiological condition, which can predict an individual's capacity to cope with environmental challenges during the postfledging life. Here, we analyzed telomere length and DNA damage in blood samples of fully grown yellow‐legged gull chicks and monitored their postfledging movements using GPS tracking. All individuals left their natal colony between 52 and 84 days of age. Those with shorter telomeres and higher levels of DNA damage left the colony earlier, possibly due to reduced parental provisioning and poor competitive ability for resources. Females and those with higher DNA damage settled farther from the natal colony. These findings suggest that physiological state at the end of the developmental period influences key decisions during the transition to independence, with potential consequences for population dynamics.

Intervertebral disc degeneration (IVDD) is a common degenerative spinal disorder and a major contributor to low back pain. Although aging is a key risk factor, the causal role of biological aging markers, such as telomere length (TL), in IVDD remains unclear. Moreover, the metabolic pathways underlying this association are largely unexplored. This study employed a 2-sample Mendelian randomization (MR) framework based on genome-wide association study summary data to investigate the causal effect of TL on IVDD risk. Genetic correlation between TL and IVDD was further evaluated using linkage disequilibrium score regression (LDSC). Additionally, we performed a network MR mediation analysis to investigate whether circulating blood metabolites mediate the relationship between TL and IVDD. Univariate MR analysis showed that TL had a significant causal effect on IVDD. (odds ratio = 0.883, 95% CI: 0.835–0.934, P = 1.15 × 10−5). LDSC revealed a significant negative genetic correlation between TL and IVDD (rg = –0.1409, SE = 0.0274, P = 2.6 × 10−7). Mediation analysis identified 16 circulating metabolites as partial mediators, with tyrosine showing the most significant mediating effect. Specifically, genetically predicted TL was negatively associated with tyrosine levels (β = –0.124, 95% CI: –0.159 to–0.089), and elevated tyrosine levels were causally associated with increased IVDD risk (β = 0.113, 95% CI: 0.055–0.172). The indirect effect mediated by tyrosine accounted for 12.78% (95% CI: 7.42%–18.14%) of the total effect of TL on IVDD. This study provides robust genetic evidence supporting a protective effect of longer TL against IVDD, and highlights tyrosine as a potential metabolic mediator in this process. These findings provide new insights about the aging-metabolism-degeneration axis in spinal health and propose telomere maintenance and amino acid metabolism as promising targets for early intervention in intervertebral disc degeneration.

Diabetes mellitus is one of the biggest public health issues of modern society, with a constant increase in prevalence. It is a complex metabolic disorder characterized by hyperglycemia, dyslipidemia, and impaired insulin signaling, leading to redox imbalance and, consequently, blood vessel dysfunction. One of the key factors in the regulation of vascular tone and contractility is the sodium/potassium adenosine triphosphatase (Na+/K+-ATPase), whose reduced expression and altered activity contribute to the development of vascular dysfunction in type 2 diabetes (T2D). Impaired redox balance and increased production of reactive oxygen species, which directly affect Na+/K+-ATPase activity, also affect the telomere-telomerase system, leading to telomere shortening, DNA damage, and cell apoptosis. Hyperbaric oxygen therapy is used to treat ischemic lesions and vascular complications of diabetes, but the molecular mechanisms underlying its effects on Na+/K+-ATPase and telomere length in T2D patients remain incompletely elucidated.

Major depressive disorder (MDD) is more prevalent in women and associated with shorter telomere length, a marker of biological ageing, and an increased risk of age-related disease. However, the precise influence of depression-related genetic and environmental risk factors on telomere dynamics remains a topic of debate. We examined leukocyte relative telomere length (RTL) and longitudinal telomere attrition in 958 women (median age: 58years) from the TwinsUK cohort. RTL was measured using quantitative PCR from up to four timepoints. Associations with self-reported depression, antidepressant use, lifestyle and socioeconomic factors, and polygenic risk scores (PGS) for MDD and comorbid age-related diseases were assessed using linear mixed models. Over a median 6-year follow-up, telomere length declined annually by 1.3% of baseline RTL. Depression showed a borderline association with shorter RTL (p=0.06), while a nominal association was observed between antidepressant use and shorter RTL (p=0.02), replicating previous findings. No significant associations were observed for PGS related to MDD. PGS for coronary artery disease was associated with shorter RTL (p=0.02), while other trait PGS showed inconsistent associations with RTL or attrition. Higher waist-to-hip ratio was associated with faster telomere attrition longitudinally (p=0.01). Our findings suggest depression and its genetic liability are not directly associated with telomere length or attrition in older women. In contrast, waist-to-hip ratio, a modifiable factor, was linked to accelerated telomere shortening, pointing to central adiposity as a potential intervention target with relevance for both mental and physical health.

We aimed to examine associations between multiple community-level social determinants of health and two biological markers: frontal alpha asymmetry (FAA) and telomere length (TL) in early childhood. We also probed pathways from community-level social determinants to biological markers and subsequent psychopathology symptoms. Using a longitudinal design, 211 families were followed during the first 2years of life. Social determinants were assessed using US Census data, FAA using resting-state electroencephalogram, TL from infant saliva samples, and child psychopathology symptoms using the ITSEA. Statistical analyses included bivariate correlations (unadjusted and with false discovery rate adjustment for multiple comparisons) and SEM. For FAA, higher rates of uninsurance (healthcare) were associated with greater right lateralization at 2months (r=-0.233, p=0.028), and higher rates of food insecurity were also associated with greater right lateralization at 9months (r=-0.250, p=0.036); however, these associations were not significant after adjustment for multiple comparisons. In our SEM model, we found that both social determinants had paths to FAA (i.e., healthcare uninsurance rates to FAA at 2months; food insecurity rates to FAA at 9months), which had paths to child psychopathology symptoms at 2years. Two community-level social determinants (greater poverty levels/lower home ownership rates) were significantly associated with shorter TL at 9months (r=-0.395, p=0.007; r=0.293, p=0.048), although only community poverty levels remained significant after adjustment for multiple comparisons.In the SEM model, community poverty levels had paths through TL at 9months to child psychopathology symptoms at 2years; home ownership rates only covaried with poverty levels. Distinct social determinant domains may influence markers of biological stress at specific time points. These findings underscore the importance of structural-level policies and early interventions addressing multiple aspects of the environment.

Ultraviolet (UV) radiation contributes to photoaging and skin cancer by causing DNA damage and generating reactive oxygen species (ROS). It also induces telomere shortening, a key factor in cellular aging. However, no studies have investigated whether sunscreen can prevent short-term telomere shortening caused by UV exposure to human skin. We have examined whether the use of a broad-spectrum sunscreen product can protect at the telomere level from the harmful effects of UV light. Human keratinocytes and a 3D skin model were exposed to 10J/cm2 of solar-simulated UV radiation under three conditions: non-exposed, exposed, and exposed with broad-spectrum sunscreen. DNA damage, assessed by γH2AX levels, was measured at 30min and 24h post-irradiation. Telomere length was evaluated by high-throughput quantitative fluorescence in situ hybridization (HT Q-FISH) at 24h post-irradiation. Histological analysis of 3D skin samples was performed using hematoxylin and eosin (H&E) staining to assess tissue integrity. A decrease in cell number, increased DNA damage, and telomere shortening, accompanied by a higher proportion of critically short telomeres, were observed in UV-exposed keratinocytes and reconstructed human skin following exposure to 10J/cm2 of solar-simulated UV radiation. The 3D skin architecture was also compromised, showing loss of keratinocytes spatial organization, evidence of epidermal cell death, and significant dermal thinning. However, cells and 3D skin samples protected with a broad-spectrum sunscreen remained comparable to non-exposed controls, showing no detectable structural or molecular alterations. These findings provide initial evidence that a broad-spectrum sunscreen product can mitigate UV-induced telomere shortening and DNA double-strand damage (DSBs), thereby preventing photodamage associated with solar exposure.

Investigating the mechanism by which telomere dysfunction affects mitochondrial homeostasis in anthracosilicosis using a Terc knockout model.

Depressive disorder in middle-aged and elderly adults: Evidence from global burden of disease and genetic analysis.

Independent and interaction effects of telomere length and life's essential 8 score on the risk of type 2 diabetes mellitus: Findings from a large prospective cohort study.

Current metabolomic aging clocks inadequately capture individual heterogeneity in biological aging trajectories, constraining their clinical utility. Here, we developed a metabolomic age clock in the UK Biobank (n=196,790) using a comprehensive panel of 249 plasma metabolites. This framework was trained to predict phenotypic age (PhenoAge), a validated composite biomarker that integrates clinical chemistry across multiple systems, and was evaluated for its utility to predict incident cardiovascular diseases (CVDs) and dementia. We found that this new measure accurately predicted actual PhenoAge (Pearson's r=0.90) and was significantly associated with the incidence of seven CVDs, including major adverse cardiovascular events, atherosclerotic cardiovascular disease, myocardial infarction, stroke, aortic stenosis, heart failure, and abdominal aortic aneurysm, but not dementia. Furthermore, metabolomic aging was associated with biological, physical, and cognitive age-related phenotypes, comprising telomere length, frailty index, and reaction time. Incorporating the metabolomic age clock with PREVENT (Predicting Risk of CVD Events) risk score modestly improved the performance, as measured by C-statistic and net reclassification index. Genetic analyses revealed 91 genomic loci and 168 genes (e.g., SERPINA1, FADS cluster), with tissue-enrichment analysis highlighting the liver's significant role in metabolic aging. By bridging metabolomic profiles with multisystem aging information, this framework provides a measure of biological aging that is associated with age-related functional status and cardiovascular risk.

Systems-level modelling of DNA damage, senescence, and stem cell dynamics in ageing.

Proteomics method for identifying POT1-associated complexes at telomeres using ChIP-Mass spectrometry.