Mean Leukocyte Telomere Length Research Articles

Investigating the relationship between the leukocyte telomere length and the incidence of atrial fibrillation: a study utilizing data from the UK Biobank

Abstract Background Atrial fibrillation (AF) is a common cardiac arrhythmia linked to a higher risk of stroke, heart failure, and death. Telomeres are DNA-protein complexes located at the end of chromosomes, and telomere length is known to be associated with biological aging and age-related disease. However, the relationship between leukocyte telomere length (LTL) and AF has been inconsistent in the literature. This study aims to clarify the relationship between LTL and AF risk using UK Biobank data and to examine the link between AF and both biological and chronological aging. Methods The UK Biobank cohort of 502,421 participants aged 40-70 was recruited across 22 UK centers from 2006-2010. After excluding i) missing values (n=32,219), ii) previous AF history (n=6,746) and iii) valvular heart disease (n=3,204), a total of 460,252 participants without AF (median age, 58.0 [interquartile range (IQR), 50.0–64.0] years; 208,543 [45.3%] male) were included. Participants were categorized into four groups based on the LTL, as determined by the adjusted T/S ratio from whole blood test. To investigate the intermediate phenotype prior to the onset of atrial fibrillation, we compared each group with LA maximum volume, LA minimum volume, LA stroke volume, and LA ejection fraction. Throughout the follow-up period, new-onset atrial fibrillation was documented. Survival analysis was conducted using Kaplan-Meier analysis and Cox proportional regression analysis. Results Among 460,252 participants without AF, the new-onset AF group had more comorbidities and lower mean LTL. Groups with shorter LTL tend to be older, and new-onset AF is more prevalent in these groups. Additionally, the incidence of comorbidities is generally higher in the groups with shorter LTL. It was observed that as the LTL shortens, the LA stroke volume decreases. The Kaplan-Meier curve demonstrated that shorter LTL correlated with increased new-onset AF risk. (Log-rank P < 0.001) However, upon examination through a multivariable univariate Cox proportional regression analysis, telomere length did not show as an independent risk factor for new-onset AF. (aHR 1.00, 95% CI 1.00-1.00, P=0.099, Adjusted T/S ratio). Conclusion Even though the incidence of AF increased as LTL shortened, there was no relationship between LTL and new-onset AF when the covariate was adjusted.

Elevated tissue status of omega-3 fatty acids protects against age-related telomere attrition in fat-1 transgenic mice

Leukocyte telomere length (LTL) is a biomarker of aging that may be influenced by dietary factors. Omega-3 fatty acids (n-3 FA) have been suggested to affect LTL. However, research on this effect has been inconclusive. The aim of the study was to test the hypothesis about the positive effect of n-3 FA on LTL. Fat-1 transgenic mice, which can convert omega-6 fatty acids (n-6 FA) to n-3 FA and have elevated levels of endogenous n-3 FA in their tissues, were used to study the effects of n-3 FA on LTL at different ages. Blood samples from 10-month-old wild-type (WT) mice (n=10) and fat-1 mice (n=10) and 3-month-old WT mice (n=5) and fat-1 mice (n=5) were used to measure relative and absolute LTL. The levels of proteins critical for telomere maintenance were examined by Western blot analysis. Fat-1 transgenic mice had longer leukocyte telomeres than their WT siblings, suggesting a slower rate of age-related telomere shortening in fat-1 mice. In animals aged 10 months, the LTL was significantly longer in fat-1 than in WT mice (mean±SEM; relative LTL: WT=1.00±0.09 vs. fat-1: 1.25±0.05, P=0.031; absolute LTL: WT=64.41±6.50 vs. fat-1: 78.53±3.86, P=0.048). The difference in LTL observed in three-month-old mice was insignificant, however the mean LTL was still longer in fat-1 mice than in the WT mice. Fat-1 mice also had abundant levels of two shelterin proteins: TRF1 (27%, P=0.028) and TRF2 (47%, P=0.040) (telomeric repeat binding factor 1 and 2) compared to WT animals. This study, for the first time in a unique animal model free of dietary confounders, has demonstrated that increased levels of n-3 FA in tissues can reduce telomere attrition. The data presented indicate the possibility of using omega-3 fatty acids to reduce accelerated telomere attrition and, consequently, counteract premature aging and reduce the risk of age-related diseases.

Deficit Accumulation Index and Biological Markers of Aging in Survivors of Childhood Cancer

Survivors of childhood cancer experience premature aging compared with community controls. The deficit accumulation index (DAI) uses readily available clinical data to measure physiological age in survivors; however, little data exist on how well deficit accumulation represents underlying biological aging among survivors of cancer. To examine the associations between the DAI and epigenetic age acceleration (EAA) and mean leukocyte telomere length (LTL). This cross-sectional study analyzed data from the St Jude Lifetime Cohort, an assessment of survivors of childhood cancer who were treated at St Jude Children's Research Hospital in Memphis, Tennessee. Data were collected between 2007 and 2016, assayed between 2014 and 2019, and analyzed between 2022 and 2023. Participants were adult survivors who were diagnosed between 1962 and 2012 and who survived 5 years or more from time of diagnosis. The analyses were restricted to survivors with European ancestry, as there were too few survivors with non-European ancestry. The DAI included 44 aging-related items, such as chronic health conditions and functional, psychosocial, and mental well-being. Item responses were summed and divided by the total number of items, resulting in a ratio ranging from 0 to 1. These DAI results were categorized based on reported associations with hospitalization and mortality: low, defined as a DAI less than 0.2; medium, defined as a DAI of 0.2 to less than 0.35; and high, defined as a DAI of 0.35 or higher. Genome-wide DNA methylation was generated from peripheral blood mononuclear cell-derived DNA. The EAA was calculated as the residuals from regressing the Levine epigenetic age on chronological age. The mean LTL was estimated using whole-genome sequencing data. This study included 2101 survivors of childhood cancer (1122 males [53.4%]; mean [SD] age, 33.9 [9.1] years; median [IQR] time since diagnosis, 25.1 [18.7-31.9] years) with European ancestry. Compared with survivors in the low DAI group, those in the high DAI group experienced 3.7 more years of EAA (β = 3.66; 95% CI, 2.47-4.85; P < .001), whereas those in the medium DAI group experienced 1.8 more years of EAA (β = 1.77; 95% CI, 0.84-2.69; P < .001), independent of treatment exposures. The EAA and DAI association was consistent across 3 common diagnoses (acute lymphoblastic leukemia, Hodgkin lymphoma, and central nervous system tumors) and across chronological age groups. For example, among acute lymphoblastic leukemia survivors, those in the medium DAI group (β = 2.27; 95% CI, 0.78-3.76; P = .001) experienced greater EAA vs those in the low DAI group. Similarly, among survivors younger than 30 years, the high DAI group experienced 4.9 more years of EAA vs the low DAI group (β = 4.95; 95% CI, 2.14-7.75; P < .001). There were no associations between mean LTL residual and the DAI. This cross-sectional study of survivors of childhood cancer showed that the DAI was associated with EAA, suggesting an underlying biological process to the accumulation of deficits. Both the DAI and EAA were effective at identifying aging phenotypes, and either may be used to measure aging and response to interventions targeting aging pathways.

Time Spent Jogging/Running and Biological Aging in 4458 U.S. Adults: An NHANES Investigation.

Telomere length is a good index of cellular aging. Longer telomeres are predictive of longer life, and healthy lifestyles are associated with longer telomeres. This study explored the relationship between time spent jogging or running each week and leukocyte telomere length (LTL) in 4458 randomly selected U.S. adults. The association was studied using data collected by the National Health and Nutrition Examination Survey (NHANES), and a cross-sectional design. Total weekly jog/run time was calculated from survey responses. From the minute totals, three categories were formed: <10 min/week, 10-74 min/week, and ≥75 min/week. Adults in the third category met the U.S. guidelines. Data were analyzed using one-way ANOVA. Partial correlation was used to adjust for differences in potential mediating factors, including demographic and lifestyle/medical factors. In the total sample, after adjusting for all the potential covariates, mean LTL significantly differed across the three jog/run categories (F = 4.1, p = 0.0272). Specifically, adults who met the guidelines via jogging and/or running had significantly longer telomeres than adults who performed no jogging/running. Adults in the middle category did not differ from the other two categories. A minimum of 75 min of jogging/running weekly is predictive of longer telomeres when compared to adults who do not jog or run regularly.

The Effect of Vitamin B12 Supplementation on Leukocyte Telomere Length in Mildly Stunted Nepalese Children: A Secondary Outcome of a Randomized Controlled Trial

BackgroundVitamin B12 is essential for deoxyribonucleic acid synthesis and genome stability. A deficiency of vitamin B12 is associated with telomere shortening, genomic aging, and increased risk of chronic disease and mortality. ObjectivesThe study aims to determine the effect of vitamin B12 supplementation on leukocyte telomere length (LTL) in infants at risk of vitamin B12 deficiency. MethodsThe study was a predefined secondary analysis of a randomized controlled trial enrolling 600 Nepalese infants aged 6 –11 mo, who were supplemented with 2 μg (2–3 recommended daily allowances) vitamin B12 or placebo daily for 1 y. At the end of the study, LTL was measured in 497 participants. Mean LTL was compared between the treatment arms in the full sample and predefined subgroups based on markers of vitamin B12 status, hemoglobin, sex, and growth indices. ResultsLTL at end-study did not differ between the vitamin B12 and placebo arm with a standardized mean difference (95% confidence interval) of 0.04 (–0.14, 0.21). There was no effect of vitamin B12 on LTL in any of the subgroups. ConclusionsProviding daily vitamin B12 for 1 y during infancy in a population at risk of vitamin B12 deficiency does not affect LTL.This trial was registered at clinicaltrials.gov as NCT02272842.

Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants.

Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5days (n = 54,180). Relative mean LTL at baseline (5-6years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity > 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171).

0466 Effect of Obstructive Sleep Apnea and CPAP on Telomere Length and its Associated Mechanisms

Abstract Introduction Growing evidence suggests the contribution of obstructive sleep apnea (OSA) in the molecular pathways of aging related to the maintenance of telomere length. The present study aimed to investigate the effect of OSA and its treatment with continuous positive airway pressure (CPAP) on the variation of telomere length and its associated mechanisms. Methods For this, a 6-month randomized, double-blind and sham-controlled clinical trial was conducted. Participants were randomized to CPAP or sham-CPAP and attended 7 visits, in which they underwent clinical assessment and had their blood collected to determine mean leukocyte telomere length (LTL) and the dosage of metabolic and inflammatory markers. Results Among 127 individuals that we contacted, 46 met the inclusion criteria. At baseline, individuals in both groups were homogeneous, including LTL (p=0.106). Adherence during the intervention was 5.29 ± 1.09 in the sham-CPAP group and 5.71 ± 0.19 in the CPAP group. After 6 months of intervention, we observed a statistically significant effect of the treatment (p=0.001) on LTL, in which the sham-CPAP group (1.0117 ± 0.1552, 0.9457 ± 0.0747, 0.8482 ± 0.2163) showed a more significant reduction than the CPAP group (1.0960 ± 0.1122, 1.0521 ± 0.1094, 1.0675 ± 0.1225). Furthermore, we found a negative correlation between delta LTL and dela TNF-α at Visit 7 and Visit 1 (rho=-0.216, p=0.003) due to the sham-CPAP intervention (rho=-0.383, p=0.009) in relation to the use of CPAP (rho=0.021, p=0.800). Conclusion We can conclude that CPAP, when compared to sham-CPAP placebo, caused an effect on LTL stability, potentially by the modulation of TNF-α. Support (if any) Our studies are supported by Associação Fundo de Incentivo à Pesquisa (AFIP), Fundação de Amparo à Pesquisa de São Paulo (FAPESP), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Conselho Nacional de Desenvolvimento Científico Tecnológico (V.A. and S.T. received CNPq fellowships).

Shorter leukocyte telomere length protects against NAFLD progression in children

Leukocyte telomere length (LTL) gets shorter with each cell division and is also sensitive to reactive oxygen species damage and inflammatory processes. Studies in adults with non-alcoholic fatty liver disease (NAFLD) have found that increased fibrosis but not ALT levels are associated with shorter LTL. Few pediatric studies have been conducted; as such, we sought to evaluate potential associations between LTL and liver disease and liver disease progression in pediatric patients. Using data from the Treatment of NAFLD in Children (TONIC) randomized controlled trial, we assessed the potential predictive relationship between LTL and liver disease progression based on two successive liver biopsies over 96 weeks. We assessed the potential relationship between LTL and child age, sex, and race/ethnicity and features of liver disease including components of histology. We subsequently evaluated predictors for improvement in non-alcoholic steatohepatitis (NASH) at 96 weeks including LTL. We also assessed predictors of lobular inflammation improvement at 96 weeks using multivariable models. Mean LTL at baseline was 1.33 ± 0.23 T/S. Increasing lobular and portal inflammation were associated with longer LTL. In multivariable models, greater lobular inflammation at baseline was associated with longer LTL (Coeff 0.03, 95% CI 0.006–0.13; p = 0.03). Longer LTL at baseline was associated with worsening lobular inflammation at 96 weeks (Coeff 2.41, 95% CI 0.78–4.04; p < 0.01). There was no association between liver fibrosis and LTL. The association between LTL and pediatric NASH does not parallel adults with no association between fibrosis stage and NASH. Conversely, longer LTL was associated with more lobular inflammation at baseline and increased lobular inflammation over the 96-week period. Longer LTL in children may indicate greater risk for future complications from NASH.

Very Low and High Levels of Vitamin D Are Associated with Shorter Leukocyte Telomere Length in 148,321 UK Biobank Participants.

Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), suggesting a close association between vitamin D and LTL. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n = 148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Serum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β = -0.018, 95% CI -0.033 to -0.003, p = 0.022) and 0.048 SD (standardized β = -0.048, 95% CI -0.083 to -0.014, p = 0.006), respectively. Additionally, the high serum 25OHD groups (>95.9 nmol/L) had 0.038 SD (standardized β = -0.038, 95% CI -0.072 to -0.004, p = 0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusions: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Our findings could be affected by unmeasured confounders. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.

PS-B09-4: SHORTER LEUKOCYTE TELOMERE LENGTH AS AN EARLY INDICATOR FOR CHRONIC KIDNEY DISEASE IN HYPERTENSIVE PATIENTS

Objective: Essential hypertension is a major risk factor for incident chronic kidney disease (CKD). This is a main reason for preference of antihypertensive medications that provide some protection against hypertension induced renal damage. Furthermore, there is abundant evidence that hypertension and CKD comorbidity worsens cardiovascular disease prognosis with increased morbidity and mortality. Onset of CKD may not be noticeable until there is evident progressive decline in the estimated glomerular filtration rate (eGFR). For this, telomere attrition may provide some early indication. Telomeres are markers of biological aging, and telomere attrition is associated with oxidative stress and inflammation. Kidney interstitial inflammation is known to play a central role in loss of renal function progressing into CKD. This study investigated the association between telomere length and renal interstitial inflammation in hypertensive patients. Design and Methods: Our study group consisted of 200 participants from the TRANScriptome of renaL humAn TissuE (TRANSLATE) study. Interstitial inflammation in human kidney tissue samples was assessed by histology. eGFR was calculated from serum creatinine using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) FORMULA. Leukocyte telomere length (LTL) was quantified using quantitative polymerase chain reaction. Results: Mean LTL was significantly shorter in hypertensive participants (2.776 ± 0.063) compared with non-hypertensive participants (3.007 ± 0.092; P = 0.041). In hypertensive participants without CKD, renal interstitial inflammation negatively associates with leukocyte telomere length (LTL) (r = -0.483, P = 0.048), and the association remained significant after adjustment for age (r = -0.479, P = 0.041). Similar results were observed after exclusion of patients with eGFR &gt; = 60 ml/min/1.73m2. In patients with eGFR &lt; 60 ml/min/1.73m2, the association remained significant after adjusting for age, sex, BMI, diabetes mellitus and smoking status (r = -1.429, P = 0.011). These results show that telomere length associates with interstitial inflammation in hypertensive patients with no apparent decrease in eGFR. Conclusions: Hypertensive participants have shorter LTL than non-hypertensive participants, and within the hypertensive group, participants with shorter telomeres are more likely to have CKD. Telomere length may provide suitable indication to help target hypertensive patients at increased risk of developing CKD.

Impact of baseline telomere length on survival and chemotherapy related toxicity in breast cancer patients receiving (neo)adjuvant anthracycline containing chemotherapy

PurposeThe aim of this study is to assess baseline mean leukocyte telomere length (TL) as a potential predictive factor for chemotherapy toxicity and a prognostic marker for long-term outcome in early breast cancer (BC) patients. Methods445 BC patients were selected, diagnosed between 2007 and 2010 with early BC and treated with (neo)adjuvant fluorouracil, epirubicin and cyclophosphamide (FEC) or with FEC and Docetaxel (FEC-D). RT-qPCR was performed on germline DNA samples collected at diagnosis before any treatment, to measure mean leukocyte TL. Uni- and multivariable logistic regression or Cox proportional hazard regression analyses were carried out to assess correlation between baseline TL and toxicity parameters (derived from the medical chart) or longer-term outcome. ResultsBaseline TL correlated with age as expected (p = 0.005), but not with febrile neutropenia (n = 97), left ventricular ejection fraction >10% decrease (n = 17) nor other toxicity endpoints measured (all p > 0.05). TL was neither associated with overall survival, breast cancer specific survival or distant disease-free survival (all p > 0.05). ConclusionsBaseline TL is not associated with chemotherapy-related toxicity nor long-term outcome in BC patients.

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.

Triglyceride-Glucose Index Correlate With Telomere Length in Healthy Adults From the National Health and Nutrition Examination Survey.

AimThe present investigation was designed to test the association between leukocyte telomere length (LTL) and two simple markers of insulin resistance, that is, homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride-glucose (TyG) index in U.S. adults without metabolic diseases.MethodsA total of 6489 U.S. adults without diabetes from NHANES 1999–2002 were analyzed. TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. HOMA-Index was calculated as fasting plasma glucose (mmol/L) × fasting serum insulin (mU/mL)/22.5. LTL was obtained using the quantitative polymerase chain reaction method. Multivariate linear regression analysis was assessed to evaluate the association of TyG index HOMA-IR with LTL. We further conducted a generalized additive model (GAM) and a fitted smoothing curve with penalized spline method.ResultsIt was found that the mean LTL was 5796.1 bp in the measured healthy adults. Overall, TyG index was significantly associated with LTL, while HOMA-IR was not. Compared with participants in tertile 1 of the TyG index, the β (95% CI) for those in the second (8.27 to 8.77) and third (≥ 8.77) were -4.31 (95% CI: -48.12~39.49) and -95.98 (95% CI: -145.08~-46.89), respectively. Subjects with TyG index ≥ 8.77 had statistically significant shorter LTL (β = -93.33, 95%CI: -134.33~-52.32), compared with TyG index < 8.77. We further explored a dose-response relation between TyG index by a decile approach [≤ 7.81 (reference), 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, 8.52-8.68, 8.68-8.83, 8.83-9.03, 9.03-9.33, and >9.33] and LTL. Five subgroups (TyG index 7.81-8.04, 8.04-8.21, 8.21-8.37, 8.37-8.52, and 8.52-8.68) did not show significant effect on LTL; while there was a significantly shorter LTL for participants with the TyG index > 8.68, supporting a threshold effect of TyG index on LTL.ConclusionsThe results suggested that higher TyG index (> 8.68) was closely related to shorter LTL and the TyG index was better associated with LTL than HOMA-IR.

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.

Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress

BackgroundShort leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress.MethodsIn this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis.ResultsA total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change − 0.03 ± 0.26, p = 0.39); 2 and 3 (− 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (− 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03).ConclusionsIn this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

Telomere and Telomerase: Biological Markers of Organic Vital Force State and Homeopathic Treatment Effectiveness.

Background Philosophical–scientific correlations described in previous studies suggest that the genome can be the biological representation of the vital force, whilst the disease-promoting epigenetic alterations would be the biological representation of the chronic miasmas. In this study, we expand the functional correlation between vital force and chromosomes, describing the mechanism of action of the telomere–telomerase complex in the context of physiological balance. Aims The aim of the work is to study the role of the telomere–telomerase complex in cell vitality, biological aging, and the health-disease process, with the goal of proposing the use of telomere length as a biomarker of the vital force state and the effectiveness of homeopathic treatment. Results Similar to the vital force, telomere length and telomerase enzyme activity play an important role in maintaining cellular vitality, biological longevity, and physiological homeostasis. Telomere shortening functions as a biomarker of vital imbalance and is associated with numerous diseases and health disorders. On the other hand, health-promotion practices neutralize the pathological shortening of the telomeres, acting therapeutically in diseases or age-dependent health disorders. Conclusions As a hypothetical biomarker of the vital force state, an intra-individual analysis of the mean leukocyte telomere length before, during, and after homeopathic treatment can be used as a biomarker of therapeutic effectiveness.

Telomere length is independently associated with all-cause mortality in chronic heart failure

ObjectivePatients with heart failure have shorter mean leucocyte telomere length (LTL), a marker of biological age, compared with healthy subjects, but it is unclear whether this is of prognostic significance....

Maternal age at last birth and leukocyte telomere length in a nationally representative population of perimenopausal and postmenopausal women.

The primary aim of this study was to evaluate if maternal age at birth of last child is associated with leukocyte telomere length in a nationally representative population of perimenopausal and postmenopausal women. We conducted a cross-sectional analysis of 1,232 women from the National Health and Nutrition Examination Survey to examine maternal age at last birth and telomere length, surveyed between 1999 and 2002. We included perimenopausal and postmenopausal women age 40 years and older. Maternal age at last live birth was self-reported, and leukocyte telomere length was measured using quantitative polymerase chain reaction. We calculated least-squares geometric mean telomere length across categories of maternal age adjusted for age, race/ethnicity, number of live births, survey cycle, and history of hysterectomy or oophorectomy. P trend < 0.05 was considered statistically significant. For hypothesis-generation, we explored modification by reproductive and sociodemographic factors. Maternal age at last birth was positively associated with telomere length: the multivariable-adjusted least-squares geometric mean leukocyte telomere length across categories of age at last birth (<25, 25-29, 30-34, 35-39, ≥40 y) was 0.90, 0.93, 0.93, 0.95, and 0.96, respectively (P trend = 0.04). There was suggestive evidence this association may be restricted to those women with one or two live births or women who reported ever using oral contraceptives (P interaction <0.10 for both). Later maternal age was associated with longer telomere length in a nationally representative population of women. These data provide new insight into the biological relationship between reproductive history and long-term health. : Video Summary:http://links.lww.com/MENO/A662.

Leukocyte telomere length is inversely associated with arterial wave reflection in 566 normotensive and never-treated hypertensive subjects.

Telomeres are short segments in chromosome ends, the length of which is reduced during cell lifecycles. We examined the association of mean leukocyte telomere length (LTL) and short telomere proportion (STP) with hemodynamic variables in normotensive and never-treated hypertensive volunteers (n=566, 19-72 years). STP and mean LTL were determined using Southern blotting, and supine hemodynamics recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. The analyses were adjusted for age, body mass index (BMI), alcohol use, smoking, plasma chemistry, and estimated glomerular filtration rate (eGFR). In univariate analyses, mean LTL and STP both correlated with age, BMI, eGFR, aortic blood pressure, augmentation index, and pulse wave velocity (p<0.05 for all). Mean LTL also correlated with systemic vascular resistance (p<0.05). In linear regression analyses of all hemodynamic variables, mean LTL was only an independent explanatory factor for augmentation index (Beta -0.006, p=0.032), while STP was not an explanatory factor for any of the hemodynamic variables, in contrast to age, BMI and several cardiovascular risk factors. To conclude, augmentation index was predominantly related with chronological aging, but also with mean LTL, suggesting that this variable of central wave reflection is a modest marker of vascular biological aging.

Abstract P246: Dimensions of and Coping Responses to Perceived Discrimination and Leukocyte Telomere Length Among African Americans in The Jackson Heart Study

Background: Leukocyte telomeres are biological markers of cellular aging. Shorter telomeres are associated with cardiovascular disease and reduced longevity. Psychosocial stress (e.g., perceived discrimination) is also associated with shorter telomeres, which contribute to aging-related illnesses. African Americans have a high burden of cardiovascular morbidity and mortality, which may be partially explained by experiences of discrimination and their resultant effects on leukocyte telomere length (LTL). Behavioral coping responses to discrimination may alter the effects of discrimination on LTL. Objective: To investigate the associations of multiple measures of and coping responses to perceived discrimination with LTL, and determine the extent to which sex, age, and educational attainment modify these associations. Hypotheses: We hypothesize that dimensions of discrimination will be inversely associated with LTL, while coping responses will be positively associated with LTL. Additionally, there will be effect modification by sex, age, and educational attainment. Methods: Jackson Heart Study participants (21-93 years) from visit 1 (2000-2004) with LTL data were utilized (n=2518). The dimensions of discrimination (everyday, lifetime, burden of lifetime, and stress from lifetime discrimination) were categorized as low (referent), moderate, and high and scored in standard deviation (SD) units. Coping responses to everyday and lifetime discrimination were categorized as emotion-focused (e.g., ignoring discrimination) and problem-focused coping (e.g., speaking out against discrimination). Multivariable linear regression analyses were performed to estimate the mean difference (standard errors-SEs) in LTL by dimensions of discrimination and coping responses. Covariates were age, sex, education, smoking and cardiovascular disease status. Effect modification by sex, age, and educational attainment was performed. Results: Mean LTL was 7.18 (kilobase pairs) (SD: 0.69). There were no statistically significant associations between dimensions of discrimination nor coping responses and mean LTL in unadjusted and fully adjusted models. However, after full adjustment, high (vs. low) stress from lifetime discrimination was associated with lower mean LTL among those aged 35-44 (vs. &lt;35) (b=-0.292, SE=0.09; p = 0.001). Moderate (vs. low) burden of lifetime discrimination was associated with higher mean LTL among women and participants age 35-44 (p=0.009). Additionally, moderate everyday and lifetime discrimination was associated with higher mean LTL among those with high school diplomas and college degrees (vs. &lt;high school diploma) (b=0.104, SE=0.053; p = 0.048 and b=0.103, SE=0.053; p = 0.047 respectively). Conclusion: Experiences of discrimination may be a risk factor for shorter LTL, when considering differences in age, sex and educational attainment.