Leukocyte Telomere Length Attrition Research Articles

Leukocyte telomere length and attrition in association with disease severity in cystic fibrosis patients.

Cystic fibrosis (CF) is characterized by chronic airway inflammation and premature aging. The link with leukocyte telomere length (LTL) as a marker of biological aging is unclear. We studied disease severity and LTL in 168 CF patients of which 85 patients had a second retrospective LTL assessment. A higher FEV1 was associated with longer LTL, with a stronger effect in men (5.08% longer LTL) compared to women (0.41% longer LTL). A higher FEV1/FVC ratio was associated with 7.05% (P=0.017) longer LTL in men. CF asthma, as defined by the treatment with inhaled corticosteroids, was associated with -6.65% shorter LTL (P=0.028). Men homozygous for the ΔF508 genotype showed a -10.48% (P=0.026) shorter LTL compared to heterozygotes. A genotype-specific non-linear association between LTL shortening and chronological age was observed. Stronger age-related LTL shortening was observed in patients homozygous for the ΔF508 genotype (P-interaction= 0.044). This work showed that disease severity in CF patients negatively influences LTL, with slightly more pronounced effects in men. The homozygous genotype for ΔF508 may play a role in LTL attrition in CF patients. Understanding factors in CF patients that accelerate biological aging provides insights into mechanisms that can extend the overall life quality in CF-diseased.

Sleep parameters might affect the attrition of leukocyte telomere length

AbstractBackgroundThe relationship between sleep parameters and longitudinal shortening of telomere length is unclear. This study aimed to investigate the relationship between sleep parameters and the shortening of leukocyte telomere length (LTL) over two years.MethodAmong the participants in the validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease, participants who measured both baseline and follow‐up (two years later) of LTL were analyzed. They were dichotomized according to the degree of LTL attrition. Clinical characteristics, including sleep duration, sleep latency, Pittsburgh Sleep Quality Index (PSQI), Stanford Sleepiness Scale, and Epworth Sleepiness Scale scores were compared between the two groups.ResultA total of 238 patients were analyzed in current study. Participants with faster LTL shortening had a shorter duration of sleep (P = 0.013) and longer sleep latency (P = 0.007). Among the components of the PSQI, subjective measures of sleep quality, sleep latency, sleep duration, and sleep efficiency were significantly worse in participants with faster LTL shortening. Multivariate logistic regression analysis showed that sleep latency (odds ratio [OR] = 1.015, confidence interval [CI] = 1.001–1.029, P = 0.029), global PSQI score (OR = 1.130, CI = 1.017–1.256, P = 0.023), shortest sleep duration (OR = 5.057, CI = 1.189–21.502; P = 0.028), and lowest sleep efficiency (OR = 8.598, CI = 1.584–46.672, P = 0.013) were independently associated with faster LTL shortening.ConclusionPoor sleep quality, specifically long sleep latency, less than 5 hours of sleep, and low sleep efficiency were associated with faster longitudinal shortening of the LTL.

Longitudinal Association of Telomere Dynamics with Obesity and Metabolic Disorders in Young Children

In adults, short leukocyte telomere length (LTL) is associated with metabolic disorders, such as obesity and diabetes mellitus type 2. These associations could stem from early life interactions between LTL and metabolic disorders. To test this hypothesis, we explored the associations between LTL and metabolic parameters as well as their evolution over time in children with or without obesity at baseline. Seventy-three (n = 73) children attending our Outpatient Clinic for the Prevention and Management of Overweight and Obesity in Childhood and Adolescence, aged 2-10 years (mean ± SD: 7.6 ± 2.0 years), were followed for 2 to 4 years. Anthropometric, clinical, and biological (including LTL by Southern blot) measurements were performed annually. Baseline LTL correlated negatively with BMI (p = 0.02), fat percentage (p = 0.01), and blood glucose (p = 0.0007). These associations persisted after adjustments for age and sex. No associations were found between LTL attrition during the follow-up period and any of the metabolic parameters. In young children, obesity and metabolic disturbances were associated with shorter telomeres but were not associated with more pronounced LTL attrition. These results suggest that short telomeres contribute to the development of obesity and metabolic disorders very early in life, which can have a major impact on health.

Polycystic ovary syndrome and leukocyte telomere length: cross-sectional and longitudinal changes.

ObjectiveTelomeres are DNA–protein complexes that protect chromosome ends from DNA damage and are surrogate biomarkers of cellular aging. Current evidence, almost entirely from cross-sectional observations, supports negative associations between leukocyte telomere length (LTL) and adverse lifestyle factors and cardiometabolic risk factors. Polycystic ovary syndrome (PCOS), the most common gynecological endocrine disorder, is associated with inflammation and oxidative stress, both factors associated with accelerated telomere attrition. We therefore hypothesized that LTL would be shorter and decrease more rapidly in women with PCOS in comparison to a control population.DesignThis is a population-based cohort study comprising women of Northern Finland Birth Cohort 1966, with clinical examinations at ages 31 and 46. The sample included self-reported PCOS (age 31, n = 190; age 46, n = 207) and referent women (age 31, n = 1054; age 46, n = 1324) with data on LTL.MethodsThe association between LTL and PCOS at ages 31 and 46 was analyzed by linear regression models adjusted for BMI, smoking, alcohol consumption and socioeconomic status at the corresponding age.ResultsWomen with PCOS had similar mean LTL at ages 31 and 46 (P > 0.4 for both). The mean LTL change between ages 31 and 46 did not differ between groups (P = 0.19). However, we observed a significant LTL attrition between ages 31 and 46 in the reference population (P < 0.001), but not in women with PCOS (P = 0.96).ConclusionsThis finding may suggest a difference in the LTL attrition rate in women with PCOS, an unexpected finding that might affect their risk of age-related disease. Further research is needed to clarify the underlying mechanisms.

RELATION BETWEEN TELOMERE DYNAMICS AND METABOLIC DISORDERS IN EARLY AGE

Objective: In adults, short leukocyte telomere length (LTL) is associated with metabolic disorders such as diabetes and obesity. The causality remains unclear since longitudinal studies do not show influence of metabolic disorders on LTL attrition. These associations could stem from early life interactions between telomere dynamics and metabolic disorders. To test this hypothesis, we measured, in obese children and their controls, LTL and its evolution over time and their associations with metabolic parameters. Design and method: 73 children aged 2–10 years (mean 7.6 ± 2.0) at inclusion were followed between 2 and 4 years (one visit/year). Anthropometric measurements (weight, height, waist and hip circumferences), a body composition analysis and a complete biology were performed annually. LTL was measured by Southern blot and LTL attrition was calculated. Scores for metabolic parameters were created based on the mean value of the parameter throughout the study. Results: Mean LTL attrition was 67 ± 8 bp/year. Baseline LTL correlated negatively with BMI score (p = 0.02), fat percentage score (p = 0.01), glycemia score (p = 0.0007), and insulinemia score (p = 0.02). These associations persisted after adjustment for age and sex. Trends for negative associations were observed between baseline LTL and waist/hip score (p = 0.07), and Hb1Ac score (p = 0.07). No association was found between LTL attrition and any of the metabolic parameters. Conclusions: In young children, metabolic parameters are negatively associated with LTL but not with LTL attrition. These results indicate that either short TL is the cause of metabolic disorders or that these metabolic disorders increased LTL attrition very early in life probably before the age of 5 years.

Association between sleep parameters and longitudinal shortening of telomere length.

Background: The relationship between sleep parameters and longitudinal shortening of telomere length is unclear. This study aimed to investigate the relationship between sleep parameters and the shortening of leukocyte telomere length (LTL) over a year.Methods: Among the participants in the validation cohort of the Korea Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease, participants who measured both baseline and follow-up (two years later) of LTL were analyzed. They were dichotomized according to the degree of LTL attrition over two years. Clinical characteristics were compared between the faster and slower LTL shortening groups (cut-off points: −0.710 kbp, n = 119 each). Multivariable logistic regression analyses were performed to determine independent relationships between faster shortening of LTL length and sleep parameters.Results: A total of 238 participants, aged 55–88 years, were included. Participants with faster LTL shortening had a shorter duration of sleep (P = 0.013) and longer sleep latency (P = 0.007). Among the components of the PSQI, subjective measures of sleep quality, sleep latency, sleep duration, and sleep efficiency were significantly worse in participants with faster LTL shortening. Multivariate logistic regression analysis showed that sleep duration (per hour, OR = 0.831, 95% CI = 0.698–0.989), sleep latency (per minute, OR = 1.013, 95% CI = 1.002–1.024), global PSQI score (OR = 1.134, 95% CI = 1.040–1.236), shortest sleep duration (OR = 5.173, 95% CI = 1.563–17.126), and lowest sleep efficiency (OR = 7.351, 95% CI = 1.943–27.946) were independently associated with faster LTL shortening.Conclusions: Poor sleep quality, specifically short sleep duration, long sleep latency, and low sleep efficiency were associated with faster longitudinal shortening of LTL.

Accelerated Biological Aging Secondary to Cardiometabolic Risk Factors Is a Predictor of Cardiovascular Mortality: A Systematic Review and Meta-analysis.

Chronological aging is one of the major risk factors of cardiovascular (CV) disease (CVD); however, the effect of biological aging on CVD and outcomes remain poorly understood. Herein, we evaluated the association between leukocyte telomere length (LTL), a marker of biological age, and CV outcomes. We searched PubMed, Embase, Ovid Medline, and Web of Science Core Collection for the studies on the association between LTL and myocardial infarction (MI), CV death, and/or CVD risk factors from inception to July 2020. Extracted data were pooled in a random-effects meta-analysis and summarized as risk ratio (RR) and corresponding 95% confidence interval (CI) per LTL tertile. A total of 32 studies (n= 144,610 participants) were included. In a pooled analysis of MI and LTL in a multivariate-adjusted model, the shortest LTL was associated with a 39% higher risk of MI (RR, 1.39; 95% CI, 1.16-1.67; P < 0.001). After adjusting for chronological age and traditional covariance, we showed a 28% increased risk of CV death in the shortest tertile of LTL (RR, 1.28; 95% CI, 1.05-1.56; P= 0.01). Analysis of the studies that investigated the association between CV risk factors and LTL (n= 7) showed that diabetes mellitus is associated with a 46% increased risk of LTL attrition (RR, 1.46; 95% CI, 1.46-2.09; P= 0.039). This study shows a strong association between LTL, a marker of biological aging, and the risk of MI and CV death. Cardiometabolic risk factors contribute to telomere attrition and therefore accelerates biological aging.

Metabolic syndrome components and leukocyte telomere length in patients with major depressive disorder

Objectives The relationship between metabolic syndrome (MetS) components and leukocyte telomere length (LTL) attrition in major depressive disorder (MDD) remains unclear. Methods We recruited 70 MDD patients (mean age: 44.6 years, 60.0% female) and 51 age- and sex-matched controls (mean age: 41.2 years, 68.6% female) to examine the associations of MetS components and LTL. Five MetS components—waist circumference, systolic/diastolic blood pressure, serum levels of fasting glucose, high-density lipoprotein cholesterol (HDL-C), and triglycerides—were assessed. LTL was measured through quantitative polymerase chain reaction. Results MDD had higher prevalence of MetS (34.3 vs. 17.6%, p=.042), low HDL-C (25.7 vs. 7.8%, p=.009) and shorter LTL (-0.038 ± 0.169 vs. 0.033 ± 0.213, p=.042). Regression analysis revealed that MDD (p=.046) and age (p=.003) associated with LTL, while a significant interaction effect of group (MDD vs. controls) × HDL-C (p=.037) was observed. Post-hoc analysis showed MDD with low HDL-C had greater LTL attrition than controls without low HDL-C (p=.020). In MDD, HDL-C dysregulation negatively correlated with LTL (p=.010); but no significance after Bonferroni correction. Conclusions HDL-C may be involved in accelerated ageing process regarding metabolic disturbance in MDD only. The relationship merits prospective investigations with larger sample size for clarification.

Obstructive Sleep Apnea as an Acceleration Trigger of Cellular Senescence Processes through Telomere Shortening.

Obstructive sleep apnea (OSA) is chronic disorder which is characterized by recurrent pauses of breathing during sleep which leads to hypoxia and its two main pathological sequelae: oxidative stress and chronic inflammation. Both are also associated with cellular senescence. As OSA patients present with higher prevalence of age-related disorders, such as atrial hypertension or diabetes mellitus type 2, a relationship between OSA and accelerated aging is observable. Furthermore, it has been established that these OSA are associated with telomere shortening. This process in OSA is likely caused by increased oxidative DNA damage due to increased reactive oxygen species levels, DNA repair disruptions, hypoxia, chronic inflammation, and circadian clock disturbances. The aim of the review is to summarize study outcomes on changes in leukocyte telomere length (LTL) in OSA patients and describe possible molecular mechanisms which connect cellular senescence and the pathophysiology of OSA. The majority of OSA patients are characterized by LTL attrition due to oxidative stress, hypoxia and inflammation, which make a kind of positive feedback loop, and circadian clock disturbance.

Longer Leukocytes Telomere Length Predicts a Significant Survival Advantage in the Elderly TRELONG Cohort, with Short Physical Performance Battery Score and Years of Education as Main Determinants for Telomere Elongation.

Leukocyte telomere length (LTL) represents a key integrating component of the cumulative effects of environmental, lifestyle, and genetic factors. A question, however, remains on whether LTL can be considered predictive for a longer and healthier life. Within the elderly prospective TRELONG cohort (n = 612), we aimed to investigate LTL as a predictor of longevity and identify the main determinants of LTL among many different factors (physiological and lifestyle characteristics, physical performance and frailty measures, chronic diseases, biochemical measurements and apolipoprotein E genotyping). We found an ever-increasing relationship between LTL quartiles and survival. Hazard ratio analysis showed that for each unit increase in LTL and Short Physical Performance Battery (SPPB) scores, the mortality risk was reduced by 22.41% and 8.78%, respectively. Conversely, male gender, Charlson Comorbidity Index, and age threatened survival, with mortality risk growing by 74.99%, 16.57% and 8.5%, respectively. Determinants of LTL elongation were SPPB scores (OR = 1.1542; p = 0.0066) and years of education (OR = 1.0958; p = 0.0065), while male gender (OR = 0.4388; p = 0.0143) and increased Disease Count Index (OR = 0.6912; p = 0.0066) were determinants of LTL attrition. Longer LTL predicts a significant survival advantage in elderly people. By identifying determinants of LTL elongation, we provided additional knowledge that could offer a potential translation into prevention strategies.

Longitudinal Associations between Discrimination, Neighborhood Social Cohesion, and Telomere Length: The Multi-Ethnic Study of Atherosclerosis (MESA).

We aimed to examine if neighborhood social cohesion moderated longitudinal associations between baseline reports of discrimination and 10-year changes in Leukocyte Telomere Length (LTL). Data are from the Multi-Ethnic Study of Atherosclerosis (MESA; N=1,064; age range 45-84 years). Baseline discrimination was measured using the Major Experiences of Discrimination Scale (MDS; none, 1 domain, ≥2 domains) and the Experiences of Discrimination Scale (EDS; none, moderate, high). Neighborhood social cohesion at baseline was assessed via a community survey within census tract defined neighborhoods. 10-year change in LTL was defined as Regression to the Mean corrected 10-year difference in the ratio of telomeric DNA to a single copy gene (T/S). In linear mixed effects models, we found that neighborhood social cohesion modified the effect of baseline reports of MDS on 10-year changes in LTL, independent of sociodemographic characteristics, health behaviors, and health conditions (p(χ 2)=0.01). Among those residing in neighborhoods with low social cohesion, experiencing major discrimination in ≥2 domains was associated with faster LTL attrition over 10-years, compared to reporting no discrimination (β=-0.03; 95% CI: -0.06, -0.003). We found no main associations for either discrimination measure and no interaction between EDS and neighborhood social cohesion. Results indicate that neighborhood social cohesion is an important dimension of the neighborhood context that may moderate the impact of major experiences of discrimination on telomere length attrition. These findings help advance our understanding of the integral role that neighborhood environments play in attenuating the effect of discrimination on accelerated cell aging.

Association Between Body Weight and Telomere Length Is Predominantly Mediated Through C-Reactive Protein.

Both obesity and inflammation are related to accelerated aging. It is not yet known whether inflammation mediates the effects of obesity on aging. This work aims to dissect the direct effect of body mass index (BMI) and its indirect effect through C-reactive protein (CRP) on leukocyte telomere length (LTL) to determine the mediation effect of CRP on the BMI-LTL association. The study cohort included 5451 adults (1404 Mexican American, 3114 White, and 933 Black individuals; 53.5% male; mean age = 49.2 years) from the 1999 to 2002 National Health and Nutrition Examination Survey. General mediation models were used to examine the mediation effect of CRP on the BMI-LTL association. After adjusting for age, race, sex, physical activity, alcohol use, and serum cotinine, the total effect of BMI on LTL was significant (standardized regression coefficient, β = -.054, P < .001) without CRP included in the model. With inclusion of CRP in the model, the indirect effect of BMI on LTL through CRP was estimated at β equal to -.023 (P < .001), and the direct effect of BMI on LTL in its absolute value decreased to β equal to -.031 (P = .025). The mediation effect of CRP was estimated at 42.6%. The mediation model parameters did not differ significantly between race and sex groups. These results suggest that the inverse BMI-LTL association is partly mediated by obesity-induced inflammation. The significant direct effect of BMI on LTL with removal of the mediation effect through CRP indicates that obesity is associated with LTL attrition also through other noninflammatory mechanisms.

Longer Leukocyte Telomere Length Predicts Stronger Response to a Workplace Sugar-Sweetened Beverage Sales Ban: An Exploratory Study.

ABSTRACTBackgroundShorter leukocyte telomere length (LTL) is associated with increased risk of a number of metabolic diseases including insulin resistance and the development of type 2 diabetes mellitus. Shorter LTL is also associated with stress reactivity suggestive of a possible role for LTL to predict response to behavioral interventions. However, few studies have evaluated how interventions, such as weight loss or dietary changes, are associated with LTL changes or whether LTL can predict behavioral responses to interventions.ObjectivesWe evaluated metabolic changes in relation to LTL changes and LTL at baseline in a cohort of at-risk adults in response to a 10-mo workplace-based sugar-sweetened beverage (SSB) intervention.MethodsAt baseline, metabolic health and LTL measurements were assessed through standard blood draws on 212 participants. Multivariable linear regression models were used to assess changes in anthropometrics, SSB consumption, and 13 blood-based metabolic risk factors, in relation to LTL at baseline and changes in LTL.ResultsLonger LTL at baseline was associated with decreases in SSB consumption over the 6-mo follow-up period (B = −29.67; P = 0.04). Slower LTL attrition rates were associated with decreases in waist circumference (B = −0.27; P = 0.03), HDL cholesterol (B = −0.20; P = 0.05), and apoA1 (B = −0.09; P = 0.01).ConclusionsLonger LTL at baseline predicted a favorable overall response to a behavioral intervention: decreases in SSB consumption. Abdominal adiposity losses paralleled slower declines in LTL suggestive of overall health benefits, but we found differences in the relations between metabolic changes and LTL at baseline compared with LTL attrition rates. Longer LTL may be a proxy marker of a positive behavioral response.This trial was registered at clinicaltrials.gov as NCT02585336.

Telomere length as a function of age at population level parallels human survival curves.

Telomeres are subject to age related shortening which can be accelerated by oxidative stress and inflammation. Many studies have reported an inverse correlation between telomere length and survival, but such inverse correlation has not been always confirmed in different populations. We analyzed the trend of Leukocyte Telomere Length (LTL) as a function of age in a cohort of 516 subjects aged 65-106 years from Southern Italy. The trend of LTL obtained was quite similar to demographic survival curves reported with data of western societies. We observed a decrease of LTL after 70 years of age and then an increase after 92 years, in agreement with the sharp decrease of survival after 70 years of age and its increase after 90 years, due to the deceleration of mortality at old ages. Our data suggest that a generalized LTL attrition after 70 years of age, associated to organismal decline, affects most of the population. Such generalized attrition may exacerbate senescence in these subjects, predisposing them to high mortality risk. Conversely, the subjects with better physical conditions, experience a lower attrition and, consequently, a delayed senescence, contributing to the deceleration of mortality which has been observed among very old subjects in modern societies.

Inverse relationship between leukocyte telomere length attrition and blood mitochondrial DNA content loss over time.

Leukocyte telomere length (LTL) and whole blood mitochondrial DNA (WB mtDNA) content are aging markers impacted by chronic diseases such as human immunodeficiency virus (HIV) infection. We characterized the relationship between these two markers in 312 women ≥12 years of age living with HIV and 300 HIV-negative controls. We found no relationship between the two markers cross-sectionally. In multivariable models, age, ethnicity, HIV, and tobacco smoking were independently associated with shorter LTL, and the former three with lower WB mtDNA. Longitudinally, among a subgroup of 228 HIV participants and 68 HIV-negative controls with ≥2 biospecimens ≥1 year apart, an inverted pattern was observed between the rates of change in LTL and WB mtDNA content per year, whereby faster decline of one was associated with the preservation of the other. Furthermore, if HIV viral control was not maintained between visits, increased rates of both LTL attrition and WB mtDNA loss were observed. We describe a novel relationship between two established aging markers, whereby rates of change in LTL and WB mtDNA are inversely related. Our findings highlight the importance of maintaining HIV viral control, the complementary longitudinal relationship between the two markers, and the need to consider both in aging studies.

TERC Variants Associated with Short Leukocyte Telomeres: Implication of Higher Early Life Leukocyte Telomere Attrition as Assessed by the Blood-and-Muscle Model.

Short leukocyte telomere length (LTL) is associated with atherosclerotic cardiovascular disease (ASCVD). Mendelian randomisation studies, using single nucleotide polymorphisms (SNPs) associated with short LTL, infer a causal role of LTL in ASCVD. Recent results, using the blood-and-muscle model, indicate that higher early life LTL attrition, as estimated by the ratio between LTL and skeletal muscle telomere length (MTL), rather than short LTL at conception, as estimated by MTL, should be responsible of the ASCVD-LTL connection. We combined LTL and MTL measurements and SNPs profiling in 402 individuals to determine if 15 SNPs classically described as associated with short LTL at adult age were rather responsible for higher LTL attrition during early life than for shorter LTL at birth. Two of these SNPs (rs12696304 and rs10936599) were associated with LTL in our cohort (p = 0.027 and p = 0.025, respectively). These SNPs, both located on the TERC gene, were associated with the LTL/MTL ratio (p = 0.007 and p = 0.037, respectively), but not with MTL (p = 0.78 and p = 0.32 respectively). These results suggest that SNPs located on genes coding for telomere maintenance proteins may contribute to a higher LTL attrition during the highly replicative first years of life and have an impact later on the development of ASCVD.

Shortened Leukocyte Telomere Length Associates with an Increased Prevalence of Chronic Health Conditions among Survivors of Childhood Cancer: A Report from the St. Jude Lifetime Cohort.

We aimed to analyze and compare leukocyte telomere length (LTL) and age-dependent LTL attrition between childhood cancer survivors and noncancer controls, and to evaluate the associations of LTL with treatment exposures, chronic health conditions (CHC), and health behaviors among survivors. We included 2,427 survivors and 293 noncancer controls of European ancestry, drawn from the participants in St. Jude Lifetime Cohort Study (SJLIFE), a retrospective hospital-based study with prospective follow-up (2007-2016). Common nonneoplastic CHCs (59 types) and subsequent malignant neoplasms (5 types) were clinically assessed. LTL was measured with whole-genome sequencing data. After adjusting for age at DNA sampling, gender, genetic risk score based on 9 SNPs known to be associated with telomere length, and eigenvectors, LTL among survivors was significantly shorter both overall [adjusted mean (AM) = 6.20 kb; SE = 0.03 kb] and across diagnoses than controls (AM = 6.69 kb; SE = 0.07 kb). Among survivors, specific treatment exposures associated with shorter LTL included chest or abdominal irradiation, glucocorticoid, and vincristine chemotherapies. Significant negative associations of LTL with 14 different CHCs, and a positive association with subsequent thyroid cancer occurring out of irradiation field were identified. Health behaviors were significantly associated with LTL among survivors aged 18 to 35 years (P trend = 0.03). LTL is significantly shorter among childhood cancer survivors than noncancer controls, and is associated with CHCs and health behaviors, suggesting LTL as an aging biomarker may be a potential mechanistic target for future intervention studies designed to prevent or delay onset of CHCs in childhood cancer survivors.See related commentary by Walsh, p. 2281.

Diet-induced leukocyte telomere shortening in a baboon model for early stage atherosclerosis

Reported associations between leukocyte telomere length (LTL) attrition, diet and cardiovascular disease (CVD) are inconsistent. This study explores effects of prolonged exposure to a high cholesterol high fat (HCHF) diet on LTL in a baboon model of atherosclerosis. We measured LTL by qPCR in pedigreed baboons fed a chow (n = 105) or HCHF (n = 106) diet for 2 years, tested for effects of diet on LTL, and association between CVD risk factors and atherosclerotic lesions with LTL. Though not different at baseline, after 2 years median LTL is shorter in HCHF fed baboons (P < 0.0001). Diet predicts sex- and age-adjusted LTL and LTL attrition (P = 0.0009 and 0.0156, respectively). Serum concentrations of CVD biomarkers are associated with LTL at the 2-year endpoint and LTL accounts approximately 6% of the variance in aortic lesions (P = 0.04). Although heritable at baseline (h2 = 0.27, P = 0.027) and after 2 years (h2 = 0.46, P = 0.0038), baseline LTL does not predict lesion extent after 2 years. Atherogenic diet influences LTL, and LTL is a potential biomarker for early atherosclerosis. Prolonged exposure to an atherogenic diet decreases LTL and increases LTL attrition, and shortened LTL is associated with early-stage atherosclerosis in pedigreed baboons.

Sex-Specific Negative Association between Iron Intake and Cellular Aging Markers: Mediation Models Involving TNFα.

Background Given that the dysregulation of iron homeostasis leads to genomic instability, iron has been linked to cellular aging. However, epidemiological research on dietary iron intake and cellular aging markers is scarce. The aim of this study was to explore the relationship between dietary iron intake and cellular aging markers and to investigate whether tumor necrosis factor-α (TNFα) mediated this relationship. Methods We conducted a cross-sectional analysis with a total of 467 subjects. Detailed dietary data were obtained using 24 h food recalls. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) were assessed using real-time PCR assay. The association between dietary iron intake and cellular aging markers and TNFα and superoxide dismutase (SOD) was analyzed by Pearson correlation analysis and regression models adjusted by covariates. Simple mediation models were generated to examine whether TNFα mediated the association between iron intake and cellular aging markers using PROCESS macro Version 3.3. Results The study population contained more women than men, but their basic demographic and metabolic characteristics did not differ. After adjusting for age, LTL was the same for men and women, while mtDNAcn was lower in men. Multiple linear regression adjusted for confounding factors found that iron intake was negatively associated with LTL only in women and negatively associated with mtDNAcn only in men. Moreover, iron intake was positively associated with TNFα in both women and men but positively associated with SOD only in men. Path modeling showed that TNFα significantly mediated the indirect detrimental effect of iron intake on LTL only in women; in men, mediation of the indirect effect of iron intake on mtDNAcn by TNFα did not reach significance. Conclusions The study found sex-specific negative associations between dietary iron intake and cellular aging markers in that iron intake had deleterious effects on LTL attrition in women and mtDNAcn in men; only the former was partly mediated by TNFα. Consequently, when dietary iron intake and iron supplementation is recommended, the effects of iron imbalance on genomic stability and cellular aging markers must be considered.

Delayed sleep-onset and biological age: late sleep-onset is associated with shorter telomere length.

We evaluated the relationship between leukocyte telomere length (LTL) and sleep duration, insomnia symptoms, and circadian rhythm, to test whether sleep and chronobiological dysregulations are associated with cellular aging. Data from the Netherlands Study of Depression and Anxiety (N = 2,936) were used at two waves 6 years apart, to measure LTL. Telomeres shorten during the life span and are important biomarkers for cellular aging. LTL was assessed by qualitative polymerase chain reaction and converted into base pair number. Sleep parameters were: sleep duration and insomnia symptoms from the Insomnia Rating Scale. Circadian rhythm variables were: indication of Delayed Sleep Phase Syndrome (DSPS), mid-sleep corrected for sleep debt on free days (MSFsc), sleep-onset time, and self-reported chronotype, from the Munich Chronotype Questionnaire. Generalized estimating equations analyzed the associations between LTL, sleep, and chronobiological factors, adjusted for baseline age, sex, North European ancestry, and additionally for current smoking, depression severity, obesity, and childhood trauma. Indicators of delayed circadian rhythm showed a strong and consistent effect on LTL, after adjustment for sociodemographic and health indicators. Late MSFsc (B = -49.9, p = .004), late sleep-onset time (B = -32.4, p = .001), indication of DSPS (B = -73.8, p = .036), and moderately late chronotype in adulthood (B = -71.6, p = .003) were associated with significantly shorter LTL across both waves; whereas sleep duration and insomnia symptoms were not. Extremely early chronotype showed significantly less LTL shortening than intermediate chronotype (B = 161.40, p = .037). No predictors showed accelerated LTL attrition over 6 years. Individuals with delayed circadian rhythm have significantly shorter LTL, but not faster LTL attrition rates.