Change In Leukocyte Telomere Length Research Articles

Causal relationship between leukocyte telomere length and two cardiomyopathies based on a bidirectional Mendelian randomization approach.

This study aims to employ the Mendelian randomization (MR) approach to investigate the relationship between leukocyte telomere length (TL) and 2 prevalent forms of cardiomyopathies. Using R software (4.3.1) for MR study, independent genetic variants associated with leukocyte TL were extracted from the Integrative Epidemiology Unit database, while cardiomyopathies data were pooled from FinnGen and European Bioinformatics Institute databases. Analytical methodologies included inverse-variance weighting, MR-Egger regression, and weighted median methods. Further analyses involved MR-Egger intercept and MR-PRESSO for handling horizontal pleiotropy and Cochran Q test for study heterogeneity. Our forward Mendelian randomization study indicates a positive correlation between longer leukocyte TL and the risk of 2 forms of cardiomyopathies: the longer the leukocyte telomere, the higher is the risk of cardiomyopathies. Specifically, for hypertrophic obstructive cardiomyopathy the OR is 2.23 (95% CI: 1.19-4.14, P = .01), for hypertrophic cardiomyopathy the OR is 1.80 (95% CI: 1.14-2.85, P = .01), and for dilated cardiomyopathy the OR is 1.32 (95% CI: 1.01-1.71, P = .04). In contrast, our reverse Mendelian randomization showed that cardiomyopathies were not directly associated with TL, and the inverse-variance-weighted test was not statistically significant for any of the 3 (P > .05). The reliability tests for the forward Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, show no evidence of horizontal pleiotropy, and Cochran Q test indicates no heterogeneity. The "leave-one-out" sensitivity analysis revealed no outlier genes. The reliability tests for the reverse Mendelian randomization, including both MR-Egger intercept and MR-PRESSO tests, also indicate no genetic pleiotropy. Despite the heterogeneity shown in our study between hypertrophic cardiomyopathy and leukocyte TL, the sensitivity analysis did not identify any anomalies. Our Mendelian randomization study suggests that longer leukocyte TL is associated with an increased risk of hypertrophic obstructive cardiomyopathy, hypertrophic cardiomyopathy, and dilated cardiomyopathy. However, the onset of these 2 kinds of disease does not directly lead to changes in leukocyte TL.

Prenatal and early life exposure to fine particulate matter and telomere length in early childhood

Telomere length is a biomarker of molecular aging that may be impacted by air pollution exposure starting in utero. We aimed to examine the association between prenatal and early life exposure to fine particulate matter (PM2.5) and leukocyte telomere length (LTL) in children and explore sex differences. Analyses included 384 mother-child pairs enrolled in the Programming Research in Obesity, Growth, and Environmental Stressors (PROGRESS) birth cohort in Mexico City. Exposure to PM2.5 was estimated at the residential level using a satellite based spatio-temporally resolved prediction model. Average relative LTL was measured in DNA isolated from blood collected at age 4-6 years using quantitative real-time polymerase chain reaction. Linear regression models were used to examine the association between average PM2.5 across pregnancy, individual trimesters, first postnatal year, and LTL. Models were adjusted for maternal age and education at enrollment, prenatal environmental tobacco smoke exposure, child sex, age, and body mass index z-score at LTL measurement. Effect modification by sex was investigated with interaction terms and stratification. In trimester specific models, we found an association between 2nd trimester PM2.5 and elongated LTL (β: 4.34, 95%CI [0.42, 8.42], per 5μg/m3 increase). There was suggestive effect modification by sex on average 2nd trimester PM2.5 with stronger associations seen in females compared to males (β: 7.12, [95%CI: 0.98, 13.6] and β: 1.43 [95%CI: -3.46, 6.57]) per 5μg/m3 increase respectively. Second trimester PM2.5 levels were associated with changes in LTL in early childhood. Understanding temporal and sex differences in PM2.5 exposure may provide insights into telomere dynamics over early life.

Leukocyte Telomere Length and Mitochondrial DNA Copy Number in Treatment-Resistant Depression and Response to Electroconvulsive Therapy: A Pilot Longitudinal Study.

In this study, we investigated if changes in leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-cn), 2 markers of cellular aging, are associated with treatment-resistant depression (TRD) and with response to electroconvulsive therapy (ECT). LTL and mtDNA-cn were measured in 31 TRD patients before (T0), 1 week (T1), and 4 weeks (T2) after the ECT course, as well as in a sample of 65 healthy controls. TRD patients had significantly shorter LTL and higher mtDNA-cn compared with healthy controls at baseline. In the TRD sample, LTL was inversely correlated with Montgomery-Åsberg Depression Rating Scale scores at baseline. Baseline levels of LTL or mtDNA-cn were not correlated with response to ECT. Similarly, changes in LTL or mtDNA-cn were not associated with response to ECT either when considered as a dichotomous trait (responders vs nonresponders) or as a percentage change in symptoms improvements. Ours is the first longitudinal study exploring the role of LTL and mtDNA-cn in response to ECT. Findings of this pilot investigation suggest that LTL and mtDNA-cn may constitute disease biomarkers for TRD but are not involved in response to ECT.

Associations between historical and contemporary measures of structural racism and leukocyte telomere length: The Multi-Ethnic Study of Atherosclerosis (MESA)

We assessed the link between two manifestations of structural racism-historical redlining and contemporary racial residential segregation-and baseline and 10-year changes in leukocyte telomere length (LTL). We used data on Black and Hispanic/Latinx participants from Exams I and V of the Multi-Ethnic Study of Atherosclerosis Stress Ancillary Study (N=741, age range=45-84 years). LTL was defined as the ratio of telomeric DNA to a single copy gene (T/S), and 10-year changes were adjusted for regression to the mean. We used 1930s Home Owners' Loan Corporation maps to assign three historical redlining grades (A&B: best/still desirable, C: declining, D: hazardous/redlined) to participants' neighborhoods (census-tracts) at baseline. The Getis-Ord Gi∗ statistic was used to evaluate census-tract level baseline residential segregation (low/moderate/high). In mixed-effects regression models accounting for neighborhood clustering, individual characteristics, and current neighborhood environments, those living in highly segregated Black neighborhoods had 0.08 shorter baseline LTL (95% CI: -0.13, -0.04), than those residing in the least segregated neighborhoods. We did not find a relationship between residing in segregated neighborhoods and 10-year LTL changes, and associations between residing in historically redlined neighborhoods and both baseline LTL and 10-year changes in LTL were null. Across discriminatory disinvestment trajectories examined, individuals residing in highly segregated but non-redlined neighborhoods had 0.6 shorter baseline LTL than individuals residing in non-redlined neighborhoods with low/moderate segregation (95% CI: -0.12, -0.01). Our results highlight the impact of racial segregation on cellular aging and underscore the need to ameliorate structural inequities within segregated neighborhoods.

Association between osteoporosis and the rate of telomere shortening.

A shorter leukocyte telomere length (LTL) is reported to be associated with age-related diseases, including osteoporosis. Many studies have tried identifying the association between LTL and osteoporosis, although it remains controversial. This study aimed to determine whether osteoporosis is independently associated with LTL shortening in a prospective longitudinal cohort. The KBASE study is an independent multicenter prospective cohort in South Korea, which began in 2014. We compared the LTL values for each participant at baseline and over a 2-year follow-up period. Boxplots were used to demonstrate the differences in the change in LTL over a 2-year follow-up according to osteoporosis. Multivariable linear regression was conducted to identify whether osteoporosis is independently associated with the rate of telomere shortening. A total of 233 subjects (from 55 to 88 years) from the KBASE cohort were finally enrolled in the study. We observed that the LTL decreased by approximately 1.2 kbp over 2 years. While the LTL decreased as age increased, the rate of LTL shortening did not increase with age. Multivariable linear regression analysis indicated that only osteoporosis was independently associated with rapid LTL shortening over 2 years (B, -8.08; p = 0.038). We sought to identify an association between osteoporosis and LTL shortening in an independent prospective cohort. We found that participants with osteoporosis had significantly faster LTL shortening over 2 years than those without osteoporosis. We hope this study will help elucidate the underlying mechanisms in the relationship between LTL and osteoporosis in the future.

Mitigating cellular aging and enhancing cognitive functionality: visual arts-mediated Cognitive Activation Therapy in neurocognitive disorders.

The growing phenomenon of population aging is redefining demographic dynamics, intensifying age-related conditions, especially dementia, projected to triple by 2050 with an enormous global economic burden. This study investigates visual arts-mediated Cognitive Activation Therapy (CAT) as a non-pharmacological CAT intervention targets both biological aging [leukocyte telomere length (LTL), DNA methylation age (DNAmAge)] and cognitive functionality. Aligning with a broader trend of integrating non-pharmacological approaches into dementia care. The longitudinal study involved 20 patients with mild to moderate neurocognitive disorders. Cognitive and functional assessments, and biological aging markers -i.e., LTL and DNAmAge- were analyzed before and after CAT intervention. Change in LTL was positively correlated with days of treatment (p =0.0518). LTL significantly elongated after intervention (p =0.0269), especially in men (p =0.0142), correlating with younger age (p =0.0357), and higher education (p =0.0008). DNAmAge remained instead stable post-treatment. Cognitive and functional improvements were observed for Copy of complex geometric figure, Progressive Silhouettes, Position Discrimination, Communication Activities of Daily Living-Second edition, Direct Functional Status (p < 0.0001) and Object decision (p =0.0594), but no correlations were found between LTL and cognitive gains. Visual arts-mediated CAT effectively mitigates cellular aging, especially in men, by elongating LTL. These findings underscore the potential of non-pharmacological interventions in enhancing cognitive and functional status and general well-being in dementia care. Further research with larger and longer-term studies is essential for validation.

Leukocyte telomere length and sarcopenia-related traits: A bidirectional Mendelian randomization study.

Accumulating evidence indicated that leukocyte telomere length (LTL) was related to sarcopenia. However, it is still not clear whether the association of changes in LTL with sarcopenia is likely to be causal, or could be explained by reverse causality. Thus, we carried on bidirectional Mendelian randomization (MR) and multivariable MR analyses to identify the causal relationship between LTL and sarcopenia-related traits. Summary-level data and independent variants used as instruments came from large genome-wide association studies of LTL (472,174 participants), appendicular lean mass (450,243 participants), low grip strength (256,523 participants), and walking pace (450,967 participants). We identified suggestive association of longer LTL with larger appendicular lean mass [odds ratio (OR) = 1.053; 95% confidence interval (CI), 1.009-1.099; P = 0.018], and causal association of longer LTL with a lower risk of low grip strength (OR = 0.915; 95% CI, 0.860-0.974; P = 0.005). In the reverse MR analysis, we also observed a positive causal association between walking pace and LTL (OR = 1.252; 95% CI, 1.121-1.397; P < 0.001). Similar results can be repeated in sensitivity analyses. While in the multivariable MR analysis, the estimate of the impact of walking pace on LTL underwent a transformation after adjusting for T2DM (OR = 1.141; 95%CI: 0.989-1.317; P = 0.070). The current MR analysis supported a causal relationship between shorter telomere length and both low muscle mass and strength. Additionally, walking pace may affect LTL through T2DM.

Changes in leukocyte telomere length among children with obesity participating in a behavioural weight control program.

To examine changes in leukocyte telomere length (LTL) during and after a behavioural weight control program for children with obesity. We measured LTL among a cohort of 158 children 8-12 years of age with a body mass index greater than or equal to the 95th percentile for age and sex. Children were 55% female, 29% white, 52% Latinx, 8% Asian and 11% Pacific Islander, other or multiethnic. All children participated in a 6-month, family-based, group behavioural weight control program and were assessed before treatment, after treatment and 1 year after the end of treatment. To test the sample population slope of LTL over the intervention and maintenance time periods, we fit spline mixed-effect regression models. LTL increased an average of 0.09 T/S units per year (95% confidence interval [CI] 0.04 to 0.13; p = 0.0001) during the weight control program intervention period, followed by an average decline of -0.05 T/S units per year (95% CI -0.08 to -0.03; p < 0.0001) during the 1 year of follow-up after the completion of the intervention. Among 26 social, psychological, behavioural and physiological factors we examined, we did not find any predictors of these changes. LTL increased in response to a behavioural weight control program among children with obesity, suggesting an impact on biological health and cellular aging from participation in a behavioural weight control intervention. LTL may be a useful biomarker for assessing changes in response to behavioural interventions.

Investigating the impact of metabolic syndrome traits on telomere length: a Mendelian randomization study.

Observational studies have reported bidirectional associations between metabolic syndrome (MetS) traits and short leukocyte telomere length (LTL), a TL marker in somatic tissues and a proposed risk factor for age-related degenerative diseases. However, in Mendelian randomization studies, longer LTL has been paradoxically associated with higher MetS risk. This study investigated the hypothesis that shorter LTL might be a consequence of metabolic dysfunction. This study undertook univariable and multivariable Mendelian randomization. As instrumental variables for MetS traits, all of the genome-wide significant independent signals identified in genome-wide association studies for anthropometric, glycemic, lipid, and blood pressure traits conducted in European individuals were used. Summary-level data for LTL were obtained from a genome-wide association study conducted in the UK Biobank. Higher BMI was associated with shorter LTL (β = -0.039, 95% CI: -0.058 to -0.020, p = 5 × 10-5 ) equivalent to 1.70 years of age-related LTL change. In contrast, higher low-density lipoprotein cholesterol was associated with longer LTL (β = 0.022, 95% CI: 0.007 to 0.037, p = 0.003) equivalent to 0.96 years of age-related LTL change. Mechanistically, increased low-grade systemic inflammation, as measured by circulating C-reactive protein, and lower circulating linoleic acid levels might link higher BMI to shorter LTL. Overweight and obesity might promote the development of aging-related degenerative diseases by accelerating telomere shortening.

Associations of green tea, coffee, and soft drink consumption with longitudinal changes in leukocyte telomere length

Whether beverage consumption is associated with longitudinal observation of telomere length remains unclear. We evaluated the association of green tea, coffee, and soft drink consumption with 6-year changes in leukocyte telomere length (LTL). The study included 1952 participants who provided whole blood samples for LTL assays during the baseline (year 2011–2012) and follow-up (year 2017–2018) periods and reported baseline information on consumption of green tea, coffee, and soft drinks. Robust regression analysis was used to analyze the association adjusted for potential confounding variables. In the results, an inverse association between green tea consumption and LTL changes from baseline, which indicate telomere shortening, was found; regression coefficient [95% confidence interval] was − 0.097 [− 0.164, − 0.029] for participants who daily consumed at least 1 cup of green tea compared with non-consumers (p value = 0.006). This association was stronger among women (versus men) and younger participants aged 50–64 years (versus older). However, a positive association between soft drink consumption and LTL shortening was observed among women (p value < 0.05). Coffee consumption was not associated with LTL changes. These findings suggested that green tea consumption may be protective against telomere shortening reflecting biological aging whereas coffee and soft drink consumption may not.

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.

Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality-Sub-Study of a Randomized Clinical Trial.

Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q10 is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q10 supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70–80 years, were included. Intervention time was 4 years, with 10 years’ follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. −0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p < 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q10 supplementation associated with reduced cardiovascular mortality.

Modifiable traits, healthy behaviours, and leukocyte telomere length: a population-based study in UK Biobank

SummaryBackgroundTelomere length is associated with risk of several age-related diseases and cancers. We aimed to investigate the extent to which telomere length might be modifiable through lifestyle and behaviour, and whether such modification has any clinical consequences.MethodsIn this population-based study, we included participants from UK Biobank who had leukocyte telomere length (LTL) measurement, ethnicity, and white blood cell count data. We investigated associations of LTL with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating between them smoking, physical activity, diet, maintenance of a healthy bodyweight, and alcohol intake, using both available and imputed data. To help interpretation, associations were summarised as the number of equivalent years of age-related change in LTL by dividing the trait β coefficients with the age β coefficient. We used mendelian randomisation to test causality of selected associations. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease might be mediated through LTL.Findings422 797 participants were available for the analysis (227 620 [53·8%] were women and 400 036 [94·6%] were White). 71 traits showed significant (p<4·27 × 10–4) associations with LTL but most were modest, equivalent to less than 1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), oily fish intake, educational attainment, and general health status retained a significant association of this magnitude, with walking pace and current smoking being additionally significant at this level of association in the imputed models. Mendelian randomisation analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the most healthy behaviours having longer LTL equivalent to about 3·5 years of age-related change in LTL than those with the least heathy behaviours (p<0·001). However, healthy behaviours explained less than 0·2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of coronary artery disease were substantially mediated through LTL.InterpretationAlthough several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy. Attempts to change telomere length through lifestyle or behavioural changes might not confer substantial clinical benefit.FundingUK Medical Research Council, UK Biotechnology and Biological Sciences Research Council, and British Heart Foundation.

Association of Telomere Length With Risk of Disease and Mortality

Telomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders. To determine the association between LTL and overall as well as disease-specific mortality and morbidity. This multicenter, community-based cohort study conducted from March 2006 to December 2010 included longitudinal follow-up (mean [SD], 12 [2] years) for 472 432 English participants from the United Kingdom Biobank (UK Biobank) and analyzed morbidity and mortality. The data were analyzed in 2021. Hazard ratios (HRs) and odds ratios for mortality and morbidity associated with a standard deviation change in LTL, adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and ethnicity. This study included a total of 472 432 English participants, of whom 54% were women (mean age, 57 years). Reduced LTL was associated with increased overall (HR, 1.08; 95% CI, 1.07-1.09), cardiovascular (HR, 1.09; 95% CI, 1.06-1.12), respiratory (HR, 1.40; 95% CI, 1.34-1.45), digestive (HR, 1.26; 95% CI, 1.19-1.33), musculoskeletal (HR, 1.51; 95% CI, 1.35-1.92), and COVID-19 (HR, 1.15; 95% CI, 1.07-1.23) mortality, but not cancer-related mortality. A total of 214 disorders were significantly overrepresented and 37 underrepresented in participants with shorter LTL. Respiratory (11%), digestive/liver-related (14%), circulatory (18%), and musculoskeletal conditions (6%), together with infections (5%), accounted for most positive associations, whereas (benign) neoplasms and endocrinologic/metabolic disorders were the most underrepresented entities. Malignant tumors, esophageal cancer, and lymphoid and myeloid leukemia were significantly more common in participants with shorter LTL, whereas brain cancer and melanoma were less prevalent. While smoking and alcohol consumption were associated with shorter LTL, additional adjustment for both factors, as well as cognitive function/major comorbid conditions, did not significantly alter the results. This cohort study found that shorter LTL was associated with a small risk increase of overall mortality, but a higher risk of mortality was associated with specific organs and diseases.

Changes in Leukocyte Telomere Length Among Children with Obesity Participating in a Behavioral Weight Control Program

Changes in Leukocyte Telomere Length Among Children with Obesity Participating in a Behavioral Weight Control Program

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.

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.

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.

Stapleless vs Stapled Gastric Bypass vs Hypocaloric Diet: a Three-Arm Randomized Controlled Trial of Body Mass Evolution with Secondary Outcomes for Telomere Length and Metabolic Syndrome Changes.

Obesity and metabolic syndrome (MetS) reduce life expectancy and are challenging to resolve. This randomized controlled trial (RCT) of patients with obesity and MetS undergoing surgical vs nonsurgical treatment compared changes in BMI, and secondarily, telomere length (as a biomarker of life expectancy) and changes in MetS components (insulin resistance, dyslipidemia, hypertension). Study design was a single-center, prospective, three-arm RCT. Group 1 patients underwent novel unstapled laparoscopic one anastomosis gastric bypass with an obstructive stapleless pouch and anastomosis (LOAGB-OSPAN); Group 2, stapled laparoscopic mini-gastric bypass-one anastomosis gastric bypass (LMGB-OAGB); and Group 3, nonsurgical weight loss therapy via a hypocaloric diet with energy restriction (HDER). The primary outcome measure was change in BMI; secondary outcome measures included change in leukocyte telomere length and other MetS components. Of 96 participants screened, 60 were randomly allocated to 3 groups: LOAGB-OSPAN group (n = 20), LMGB-OAGB group (n = 20), and HDER group (n = 20). At post-treatment month 12, respective BMI changes: BMI -12.13 (-8.34, -15.93); -16.04 (-11.7, 20.37); -2,76 (-3.84, -9.36) (p < 0.01). The two surgical groups experienced significant change in telomere length: LOAGB-OSPAN 2.02 (1.61, 2.41), p = 0.001; LMGB-OAGB 2.07 (1.72, 2.43), p = 0.001; and HDER 0.28 (0.22, 0.78), p = 0.26. The surgical groups were also more effective in treating MetS components. There were no deaths. Adverse events: LOAGB-OSPAN (n = 2) (Clavien-Dindo grade II); LMGB-OAGB (n = 8) (grade I (n = 6) and grade II (n = 2). Compared with hypocaloric diet therapy, both bariatric procedures resulted in greater BMI loss, and secondarily, a significant increase in telomere length, and greater MetS resolution. ClinicalTrials.gov , NCT03667469, registered on 11 September 2018.

Leukocyte Telomere Length in Patients with Multiple Sclerosis and Its Association with Clinical Phenotypes

Aging is a significant factor influencing the course of multiple sclerosis (MS). Accelerated telomere attrition is an indicator of premature biological aging and a potential contributor to various chronic diseases, including neurological disorders. However, there is currently a lack of studies focusing on telomere lengths in patients with MS. We measured the average leukocyte telomere length (LTL) in biobanked DNA samples of 40 relapsing-remitting MS patients (RRMS), 20 primary progressive MS patients (PPMS), and 60 healthy controls using a multiplex quantitative polymerase chain reaction method. Changes in LTL over a period of >10 years were evaluated in a subset of 10 patients. Association analyses of baseline LTL with the long-term clinical profiles of the patients were performed using inferential statistical tests and regression models adjusted for age and sex. The cross-sectional analysis revealed that the RRMS group was characterized by a significantly shorter relative LTL, on average, as compared to the PPMS group and controls. Shorter telomeres at baseline were also associated with a higher conversion rate from RRMS to secondary progressive MS (SPMS) in the 10-year follow-up. The LTL decrease over time was similar in RRMS patients and PPMS patients in the longitudinal analysis. Our data suggest a possible contributory role of accelerated telomere shortening in the pathobiology of MS. The interplay between disease-related immune system alterations, immunosenescence, and telomere dynamics deserves further investigation. New insights into the mechanisms of disease might be obtained, e.g., by exploring the distribution of telomere lengths in specific blood cell populations.