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Purpose: Leukocyte telomere length (LTL) is a biomarker of inflammation and oxidative stress that predicts chronic disease risk. Nutritional factors are related to LTL in adulthood, but these associations are not well characterized in children. We examined whether micronutrient status biomarkers were associated with LTL in school-age children. Methods: We conducted a cross-sectional study of 330 boys and 393 girls aged 5–12 years from Bogotá, Colombia. We quantified blood concentrations of hemoglobin, ferritin, zinc, vitamin A, folate, and vitamin B-12; and measured LTL using qPCR in DNA extracted from buffy coat. We estimated mean differences in LTL by quartiles of micronutrient status biomarkers and categories of relevant sociodemographic and anthropometric covariates with the use of linear regression. Results: In girls, plasma vitamin B-12 was positively associated with LTL (adjusted LTL difference between extreme vitamin B-12 quartiles = 0.11; P, trend = 0.02). LTL was also positively associated with birth order in girls (P, trend = 0.02). In boys, LTL was not related to the micronutrient status biomarkers but, unexpectedly, it was positively associated with birth weight (P = 0.02), height-for-age Z score (P, trend = 0.01), and serum C-reactive protein (P, trend = 0.01). Conclusions: LTL is associated with vitamin B-12 status among girls. LTL is also associated with birth weight, height, and C-reactive protein in boys. [ABSTRACT FROM AUTHOR]

There are controversial results if leukocyte telomere length (LTL) is related to structural brain changes and cognitive decline in aging. Here, we investigated the association between LTL and 1) global MRI correlates of brain aging such as brain parenchymal fraction (BPF) and white matter hyperintensities (WMH) load and Fazekas score as well as 2) global (g-factor) and domain-specific cognition such as attention/speed, conceptualization, memory, and visuopractical skills. In total, 909 participants of the Austrian Stroke Prevention Study with LTL, MRI, and cognitive tests were included. There were 388 (42.7%) men, and the mean age was 65.9 years. Longer LTL was significantly associated with larger BPF (β = 0.43, p < 0.001), larger WMH load (β = 0.03, p = 0.04), and score (β = 0.05, p = 0.04) after adjusting for age, sex, vascular risk factors, and ApoE4 carrier status. The effect on BPF was more significant in the subgroups of women (β = 0.51, p = 0.001), age >65 years (β = 0.58, p = 0.002), BMI ≥ 25 (β = 0.40, p = 0.004), education ≤10 years (β = 0.42, p = 0.002), hypertensives (β = 0.51, p = 0.001), cardiovascular disease (CVD) (β = 0.58, p = 0.005), non-diabetics (β = 0.42, p < 0.001), and Apoe4 non-carriers (β = 0.49, p < 0.001). The effect on WMH was significant within the hypertensives (load: β = 0.04, p = 0.02), non-diabetics (load:β = 0.03, p = 0.01; score: β = 0.06, p = 0.02), in those with education ≤10 years (load: β = 0.03, p = 0.04; score: β = 0.07, p = 0.02), in ApoE4 non-carriers (load: β = 0.03, p = 0.02; score: β = 0.07, p = 0.01) and in subjects without CVD (score: β = 0.06, p = 0.05). We only observed a significant association between LTL and the cognitive domain of attention/speed, which was confined to the subgroups of BMI ≥ 25 (β = 0.04, p = 0.05) and education ≤10 years (β = 0.04, p = 0.05). The effect of LTL on attention/speed was partly mediated in both subgroups by BPF (β = 0.02, 95% CI = 0.01:0.03) when tested by bootstrapping. Our results support a strong protective role of longer LTL on global brain volume which in turn may contribute to better cognitive functions, especially in the attention/speed domain in the elderly. [ABSTRACT FROM AUTHOR]

Background: Previous evidence suggests that plasma phospholipid fatty acids (PPFAs) and HOMA insulin resistance (HOMA-IR) are independently related to leukocyte telomere length (LTL). However, there is limited evidence of regarding the effect of their interaction on relative LTL (RLTL). Therefore, here, we aimed to determine the effect of the interaction between PPFAs and HOMA-IR on RLTL. Methods: We conducted a cross-sectional study, involving a total of 1246 subjects aged 25–74 years. PPFAs and RLTL were measured, and HOMA-IR was calculated. The effect of the interaction between PPFAs and HOMA-IR on RLTL was assessed by univariate analysis, adjusting for potential confounders. Results: In age-adjusted analyses, multivariate linear regression revealed a significant association of the levels of elaidic acid, HOMA-IR, monounsaturated fatty acids (MUFA) and omega-6 (n-6) polyunsaturated fatty acid (PUFA) with RLTL. After adjustment of age and gender, race, smoking, drinking, tea, and exercise, elaidic acid, and omega-3 (n-3) PUFA were negatively associated with RLTL, and HOMA-IR and n-6 PUFA were positively associated with RLTL. These associations were not significantly altered upon further adjustment for anthropometric and biochemical indicators. Meanwhile, the effect of the interaction of elaidic acid and HOMA-IR on RLTL was significant, and remained unchanged even after adjusting for the aforementioned potential confounders. Interestingly, individuals who had the lowest HOMA-IR and the highest elaidic acid levels presented the shortest RLTL. Conclusions: Our findings indicated that shorter RLTL was associated with lower HOMA-IR and higher elaidic acid level. These findings might open a new avenue for exploring the potential role of the interaction between elaidic acid and HOMA-IR in maintaining RLTL. [ABSTRACT FROM AUTHOR]

• Breast cancer telomerase activity in women with breast cancer is greater than that in women without. • Leukocyte telomere length is not significantly different in women with and without breast cancer. • These telomerase results do not differ in women with breast cancer from different world regions. We performed a systematic review and meta-analysis to assess whether telomerase activity and telomere length are associated with breast cancer. PubMed, Web of Science, Embase, LILACS, Scielo, Embase, and CNKI databases were searched to obtain relevant articles published through May 10, 2023, following PRISMA guidelines and a registered PROSPERO protocol (CRD42022335402). We included observational studies reporting telomerase activity or telomere length in patients with breast cancer compared with women with benign lesions or normal tissue (control women). The Newcastle–Ottawa Scale was used to evaluate the quality of studies. Data were expressed as odds ratios (OR) and 95 % confidence intervals (CI). Random effects and inverse variance methods were used to meta-analyze associations. The I 2 test was used to assess heterogeneity. The meta-analysis of telomerase shows significantly greater activity in patients with breast cancer than in those without malignancies (OR = 23.46, 95 % CI 14.07–39.11, p < 0.00001, I 2 = 72 %). There were non-significant differences in relative telomere length (OR = 1.16, 95 % CI = 0.90–1.49, p = 0.26, I 2 = 86 %) and leukocyte telomere length (OR = 2.32, 95 % CI = 0.89–6.08, p = 0.09, I 2 = 98 %) between women with and without breast cancer. In subgroup analyses by world regions of studies, both telomerase activity and telomere length displayed the same trends as in their respective meta-analyses. In sensitivity analyses, variables showed their respective same trends. Telomerase activity is higher in patients with breast cancer than in women without malignancies. There were no significant differences in either relative telomere length or leukocyte telomere length in women with and without breast cancer. PROSPERO protocol CRD42022335402. [ABSTRACT FROM AUTHOR]

Leucocyte telomere length (LTL) is a robust marker of biological aging and is associated with obesity and cardiometabolic risk factors in childhood and adolescence. We investigated the effect of a structured, comprehensive, multidisciplinary, personalized, lifestyle intervention program of healthy diet and physical exercise on LTL in 508 children and adolescents (239 males, 269 females; 282 prepubertal, 226 pubertal), aged 10.14 ± 0.13 years. Participants were classified as obese (n = 267, 52.6%), overweight (n = 174, 34.2%), or of normal BMI (n = 67, 13.2%) according to the International Obesity Task Force (IOTF) cutoff points and were studied prospectively for one year. We demonstrated that LTL increased significantly after 1 year of the lifestyle interventions, irrespective of gender, pubertal status, or body mass index (BMI). Waist circumference was the best negative predictor of LTL at initial assessment. The implementation of the lifestyle interventions also resulted in a significant improvement in clinical (BMI, BMI z-score and waist to height ratio) and body composition indices of obesity, inflammatory markers, hepatic enzymes, glycated hemoglobin (HbA1C), quantitative insulin sensitivity check index (QUICKI), and lipid profile in all participants. These findings indicate that the increased LTL may be associated with a more favorable metabolic profile and decreased morbidity later in life.

Background: Psychosocial stressors, such as perceived discrimination and depressive symptoms, may shorten telomeres and exacerbate aging-related illnesses. Methods: Participants from the Jackson Heart Study at visit 1 (2000–2004) with LTL data and Center for Epidemiological Studies-Depression (CES-D) scores (n = 580 men, n = 910 women) were utilized. The dimensions of discrimination scores (everyday, lifetime, burden of lifetime, and stress from lifetime discrimination) were standardized and categorized as low, moderate, and high. Coping responses to everyday and lifetime discrimination were categorized as passive and active coping. Multivariable linear regression analyses were performed to estimate the mean difference (standard errors-SEs) in LTL by dimensions of discrimination and coping responses stratified by CES-D scores < 16 (low) and ≥ 16 (high) and sex. Covariates were age, education, waist circumference, smoking and CVD status. Results: Neither everyday nor lifetime discrimination was associated with mean differences in LTL for men or women by levels of depressive symptoms. Burden of lifetime discrimination was marginally associated with LTL among women who reported low depressive symptoms after full adjustment (b = 0.11, SE = 0.06, p = 0.08). Passive coping with lifetime discrimination was associated with longer LTL among men who reported low depressive symptoms after full adjustment (b = 0.18, SE = 0.09, p < 0.05); and active coping with lifetime discrimination was associated with longer LTL among men who reported high depressive symptoms after full adjustment (b = 1.18, SE = 0.35, p < 0.05). Conclusions: The intersection of perceived discrimination and depressive symptomatology may be related to LTL, and the effects may vary by sex.

There is limited evidence regarding the potential risk of untargeted iron supplementation, especially among individuals who are iron-replete or have genetic hemoglobinopathies. Excess iron exposure can increase the production of reactive oxygen species, which can lead to cellular damage. We evaluated the effect of daily oral supplementation on relative leukocyte telomere length (rLTL) and blood mitochondrial DNA (mtDNA) content in non-pregnant Cambodian women (18–45 years) who received 60 mg of elemental iron as ferrous sulfate (n = 190) or a placebo (n = 186) for 12 weeks. Buffy coat rLTL and mtDNA content were quantified by monochrome multiplex quantitative polymerase chain reaction. Generalized linear mixed-effects models were used to predict the absolute and percent change in rLTL and mtDNA content after 12 weeks. Iron supplementation was not associated with an absolute or percent change in rLTL after 12 weeks compared with placebo (ß-coefficient: −0.04 [95% CI: −0.16, 0.08]; p = 0.50 and ß-coefficient: −0.96 [95% CI: −2.69, 0.77]; p = 0.28, respectively). However, iron supplementation was associated with a smaller absolute and percent increase in mtDNA content after 12 weeks compared with placebo (ß-coefficient: −11 [95% CI: −20, −2]; p = 0.02 and ß-coefficient: −11 [95% CI: −20, −1]; p= 0.02, respectively). Thus, daily oral iron supplementation for 12 weeks was associated with altered mitochondrial homeostasis in our study sample. More research is needed to understand the risk of iron exposure and the biological consequences of altered mitochondrial homeostasis in order to inform the safety of the current global supplementation policy.

The emerging evidence emphasizes red blood cell distribution width (RDW) as optimal prognostic biomarker for cardiovascular diseases. However, several clinical biases impede its clinical application. Recent recommendations suggest combining RDW with other biomarkers. Accordingly, we propose evaluating the well-recognized biomarkers of vascular aging (i.e., the leukocyte telomere length and telomerase activity, and reduced levels of endothelial progenitor cells [EPCs]) with RDW, for predicting the risk for vascular aging and onset and prognosis of age-related degenerative arterial diseases, such as sporadic ascending aorta aneurysm (AAA), characterized to have an increased incidence in old people. Consequently, in this study (and for the first time), we simultaneously investigated the relationship between RDW values, systemic inflammatory molecules, mean values of leukocyte telomere length, telomerase activity and EPCs, and the risk for vascular aging and AAA onset and prognosis. To achieve this aim, we selected 80 old and 80 young healthy subjects and 80 AAA cases. Appropriate methodologies were used for assessing blood parameters, aorta alterations, genotyping, impairment of the leukocyte telomere length, and telomerase activity. The main findings obtained demonstrated that increased RDW values along with the augmented blood levels of high-sensitive C-reactive protein and the reduced mean values of both leukocyte telomere length, telomerase activity, and EPCs are independently associated with the high risk for both vascular aging and AAA onset and prognosis. They might be used as the best predictor biomarker profile for vascular aging, and for both diagnosis and outcome of sporadic AAA. [ABSTRACT FROM AUTHOR]

Background: Overweight and obese individuals have a reduced life expectancy due to cardiovascular disease (CVD), type 2 diabetes, stroke and cancer. Systemic inflammation and premature telomere shortening have been discussed as potential mechanisms linking these conditions. We investigated the relation of subcutaneous adipose tissue (SAT) distribution to leukocyte relative telomere length (RTL). Methods: We measured RTL in 375 participants of the observational STYJOBS/EDECTA cohort (ClinicalTrials.gov Identifier NCT00482924) using a qPCR based method. SAT distribution was determined by lipometry yielding a percent body fat value and SAT thicknesses at 15 standardized locations across the entire body. A correlation analysis between RTL, age, sex, lipometry data and conventional body measures (body mass index [BMI], waist-, hip circumference, waist-to-hip ratio, waist-to-height ratio) was calculated. The strongest determinants of RTL were determined by a stepwise multiple regression analysis. Results: RTL was not associated with age or sex. RTL was significantly negatively correlated with BMI, percent body fat, waist-, hip circumference and waist-to-height ratio. Furthermore, RTL correlated with SAT at the following locations: neck, triceps, biceps, upper back, front chest, lateral chest, upper abdomen, lower abdomen, lower back, hip, front thigh, lateral thigh, rear thigh and calf. Stepwise regression analysis revealed nuchal and hip SAT as the strongest predictors of RTL. No significant association was seen between RTL and waist-to-hip ratio. Conclusions: RTL is negatively associated with parameters describing body fat composure. Nuchal and hip SAT thicknesses are the strongest predictors of RTL. Central obesity appears to correlate with premature genomic aging. [ABSTRACT FROM AUTHOR]

Purpose: Telomere length is considered a biomarker of human aging and premature morbidity and mortality which has been associated with chronic stress.Methods: We assessed the relation between perceived racism and telomere length in the Black Women's Health Study, a follow-up study of U.S. black women begun in 1995. Participants were asked about frequency of "everyday racism" (e.g., "people act as if they think you are not intelligent") and "institutional racism" (e.g., "ever treated unfairly due to race by police"). Using quantitative real-time polymerase chain reaction assay, relative telomere lengths (RTL) were measured as the copy number ratio of telomere repeat to a single control gene in 997 participants. Associations of racism variables with log-RTL were estimated by multivariable linear regression, with adjustment for age at blood draw and potential confounders.Results: Participants were aged 40-70 years (mean = 55.6 years), and mean telomere length was 0.77 (range 0.21-1.38). In stratified analyses, there was an inverse association between everyday racism and log-RTL among women who did not discuss their experiences of racism with others (β = -0.1104; 95% CI = -0.2140 to -0.0067; P = .045).Conclusions: Everyday racism was associated with shorter telomere length among women who reported not discussing those experiences with others. [ABSTRACT FROM AUTHOR]

Major psychiatric disorders are linked to early mortality and patients afflicted with these ailments demonstrate an increased risk of developing physical diseases that are characteristically seen in the elderly. Psychiatric conditions like major depressive disorder, bipolar disorder and schizophrenia may be associated with accelerated cellular aging, indicated by shortened leukocyte telomere length (LTL), which could underlie this connection. Telomere shortening occurs with repeated cell division and is reflective of a cell’s mitotic history. It is also influenced by cumulative exposure to inflammation and oxidative stress as well as the availability of telomerase, the telomere-lengthening enzyme. Precariously short telomeres can cause cells to undergo senescence, apoptosis or genomic instability; shorter LTL correlates with compromised general health and foretells mortality. Important data specify that LTL may be reduced in principal psychiatric illnesses, possibly in proportion to exposure to the ailment. Telomerase, as measured in peripheral blood monocytes, has been less well characterized in psychiatric illnesses, but a role in mood disorder has been suggested by preclinical and clinical studies. In this manuscript, the most recent studies on LTL and telomerase activity in mood disorders are comprehensively reviewed, potential mediators are discussed, and future directions are suggested. An enhanced comprehension of cellular aging in psychiatric illnesses could lead to their re-conceptualizing as systemic ailments with manifestations both inside and outside the brain. At the same time this paradigm shift could identify new treatment targets, helpful in bringing about lasting cures to innumerable sufferers across the globe. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the effect of High Intensity Interval Training (HIIT) versus Aerobic Exercise (A-Ex) following 12 wks of training. Twenty-one Sprague Dawley rats (11 to 13 months) were assigned to 3 groups: (1) Control Group (no exercise); (2) A-Ex Group; and (3) HIIT Group. The A-Ex Group was submitted to treadmill exercise at a speed of 20 m⋅min-1 with a rest period of 90 sec every 5 min for 20 min 5 d⋅wk-1. The HIIT Group was submitted to treadmill exercise at a speed of 35 m⋅min-1 with a rest period of 90 sec every 5 min for 15 min 5 d⋅wk-1. At weeks 4 and 12, relative Leukocyte Telomere Length (LTL) was compared to week 4 of the Control Group using q-RT-PCR. It was shown that relative LTL in the A-Ex Group at week 4 and 12 was significantly longer compared to week 4 of the Control Group (P<0.05), but no significant difference in the HIIT Group compared to the Control Group (P>0.05). We concluded that 12 wks of aerobic and HIIT exercise both cause lengthening of relative LTL. Aerobic exercise has a better effect compared to HIIT in relation to changes in relative LTL. [ABSTRACT FROM AUTHOR]

Recent research has shown that markers of biological age, such as leukocyte telomere length (LTL), epigenetic clocks and the frailty index (FI) are predictive of mortality and age-related diseases. However, whether these markers associate with the need for care in old age, thereby having utility in reflecting dependency, is unclear. This study was undertaken to analyze whether LTL, two epigenetic clocks—the DNA methylation age (DNAmAge) and DNAm PhenoAge—and the FI are associated with the need for regular care in up to 604 individuals (aged 48–94 years) participating in the Swedish Adoption/Twin Study of Aging. Need for regular care was defined as receiving formal or informal help in daily routines at least once per week. Logistic regression adjusted for age, sex and education was used in the analysis. The predictive accuracies, assessed as the area under the curve (AUC) for the significant biological age measures were further compared to the accuracies of the limitations in activities of daily living (ADL) and instrumental ADL (IADL). Neither LTL nor the epigenetic clocks were associated with the need for care, whereas the FI was; odds ratio for 10% increase in FI 3.54 (95% confidence interval 2.32–5.41). The FI also demonstrated higher predictive accuracy than the ADL score (FI AUC 0.80 vs. ADL score AUC 0.62; p < 0.001 for equality of the AUCs), whereas the difference between FI AUC (0.80) and IADL score AUC (0.75) was not significant (p = 0.238). The FI might thus be a useful marker for the need for care. [ABSTRACT FROM AUTHOR]

Objective: Telomere length has emerged as a cumulative marker for lifestyle, psychosocial stress, and cytotoxic environments. We aimed to examine the possible association between leukocyte telomere length (LTL) and completed suicide.Methods: This study included 71 suicide completers and 117 healthy controls for whom LTL was determined by the ratio of the telomere repeat copy number to the single-copy gene copy number (T/S ratio). We compared the LTL between the suicide completers and the healthy controls and estimated the odds ratio (OR) for suicide for each age group, applying a generalized estimating equation (GEE).Results: LTL was significantly shortened in the suicide completers as compared with the controls, overall subjects, or within-age categories (≤29 and 30-49 years). Furthermore, a longer LTL was associated with significantly decreased odds of completed suicide for those aged ≤29 years and 30-49 years (OR = 0.11, 95% confidence interval [CI] 0.03-0.37, p < .001 for the ≤29-year age group; OR = 0.54, 95% CI 0.34-0.84, p = .006 for the 30- to 49-year age group).Conclusions: This study provides evidence regarding the relationship between shortened LTL and completed suicide, especially in those aged <50 years. Future research should further assess potential confounders and examine underlying mechanisms. [ABSTRACT FROM AUTHOR]

Highlights • Successful aging mediated the association between chronological age and telomere length. • Lower socioeconomic status was associated with larger age-related decreases in telomere length. • The cognitive functioning dimension of successful aging was uniquely related to telomere length. Abstract In a rapidly greying world, the notion that some individuals maintain successful aging trajectories, viz. high physical, cognitive, emotional, and social functioning in older age, is increasingly germane. Biomarkers of such successful aging are increasingly sought. Leukocyte telomere length (LTL), an emerging yardstick of cellular aging that is influenced by but distinct from chronological age, may also be associated to successful aging. Furthermore, given that socio-economic status (SES) influences successful aging trajectories, socioeconomic status may also moderate the association between chronological age and LTL. The goals of this study are to examine 1) whether successful aging is associated with LTL; 2) whether successful aging accounts for age-related LTL and 3) whether SES moderates the effect of age on LTL. Singaporean Chinese (n = 353) aged 65–80 completed a multidimensional assessment of successful aging and provided blood samples for LTL analysis. Results show that LTL negatively correlates with chronological age and positively correlates with successful aging. Successful aging mediates the association between chronological age and LTL. Moderated mediation analyses show that lower SES is associated with stronger negative associations of chronological age with successful aging and LTL. Moreover, the cognitive functioning dimension of successful aging is uniquely associated with LTL and its association with chronological age is moderated by SES. This study provides evidence that among older Singaporean Chinese with lower SES, declines in successful aging and in cognitive functioning are linked to age-related LTL shortening and hence to accelerated aging at the cellular level. [ABSTRACT FROM AUTHOR]

In utero particulate matter exposure produces oxidative stress that impacts cellular processes that include telomere biology. Newborn telomere length is likely critical to an individual's telomere biology; reduction in this initial telomere setting may signal increased susceptibility to adverse outcomes later in life. We examined associations between prenatal particulate matter with diameter ≤2.5 µm (PM 2.5) and relative leukocyte telomere length (LTL) measured in cord blood using a data-driven approach to characterize sensitive windows of prenatal PM 2.5 effects and explore sex differences. Women who were residents of Mexico City and affiliated with the Mexican Social Security System were recruited during pregnancy (n = 423 for analyses). Mothers' prenatal exposure to PM 2.5 was estimated based on residence during pregnancy using a validated satellite-based spatio-temporally resolved prediction model. Leukocyte DNA was extracted from cord blood obtained at delivery. Duplex quantitative polymerase chain reaction was used to compare the relative amplification of the telomere repeat copy number to single gene (albumin) copy number. A distributed lag model incorporating weekly averages for PM 2.5 over gestation was used in order to explore sensitive windows. Sex-specific associations were examined using Bayesian distributed lag interaction models. In models that included child's sex, mother's age at delivery, prenatal environmental tobacco smoke exposure, pre-pregnancy BMI, gestational age, birth season and assay batch, we found significant associations between higher PM 2.5 exposure during early pregnancy (4–9 weeks) and shorter LTL in cord blood. We also identified two more windows at 14–19 and 34–36 weeks in which increased PM 2.5 exposure was associated with longer LTL. In stratified analyses, the mean and cumulative associations between PM 2.5 and shortened LTL were stronger in girls when compared to boys. Increased PM 2.5 during specific prenatal windows was associated with shorter LTL and longer LTL. PM 2.5 was more strongly associated with shortened LTL in girls when compared to boys. Understanding sex and temporal differences in response to air pollution may provide unique insight into mechanisms. • Examined sensitive windows of prenatal PM 2.5 exposure on LTL in cord blood. • Sensitive window identified at gestational weeks 4–9, 14–19 and 34–36. • Findings suggest sex-specific associations. • PM 2.5 more strongly associated with shortened LTL in girls compared to boys. [ABSTRACT FROM AUTHOR]

Leukocyte telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN), as hallmarks of cellular aging, may be involved in the development of coronary artery disease (CAD) by modulating oxidative stress. This study aimed to investigate the effects of leukocyte TL and mtDNA-CN alone or in combination on CAD risk and severity in the Chinese population. In this two-stage case-control study with 1511 CAD patients and 1553 controls, leukocyte TL and mtDNA-CN were determined by a quantitative PCR assay. Three oxidative parameters, including leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG), plasma malondialdehyde, and plasma reactive oxygen species (ROS), were quantified by ELISA or colorimetric kits in a subset of 129 cases and 129 controls. In the combined cohort, each 1-SD decrease in TL and mtDNA-CN was significantly associated with a 1.17-fold and 1.14-fold increased risk of CAD (p < 0.001 for all), respectively, after adjusting for confounders. The aggregated score, which reflected the cumulative dosage of the tertiles of TL and mtDNA-CN, showed inverse dose-response correlations with CAD risk (p trend < 0.001), and severity, as determined by the severity of clinical presentations (p trend = 0.037), the presence of multi-vessel CAD (p trend = 0.004), and modified Gensini scores (p trend = 0.009). Similar dose-response relations of the aggregated score to leukocyte 8-OHdG and plasma ROS were also identified. Our data suggested reductions in both TL and mtDNA-CN as independent risk factors for CAD. The combination of TL and mtDNA-CN might jointly contribute to CAD risk, CAD severity, and oxidative stress. Image 1 • Lower leukocyte telomere length (TL) and mitochondrial DNA copy number (mtDNA-CN) independently increased coronary artery disease (CAD) risk. • The aggregated score of TL and mtDNA-CN may better predict CAD risk and severity. • The aggregated score may inversely correlate with markers of oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: Telomere length-associated SNPs have been associated with incidence and survival rates for malignant brain tumors such as glioma. Here, we study the influence of genetically determined lymphocyte telomere length (LTL) by comparing telomerase associated SNPs between the most common non-malignant brain tumor, i.e. meningioma, and healthy controls. Methods/patients: One thousand fifty-three (1053) surgically treated meningioma patients and 4437 controls of Western European ancestry were included. Germline DNA was genotyped for 8 SNPs previously significantly associated with LTL. Genotypically-estimated LTL was then calculated by summing each SNP's genotypically-specified telomere length increase in base pairs (bp) for each person. Odds ratios for genotypically-estimated LTL in meningioma cases and controls were evaluated using logistic regression with the first two ancestral principal components and sex as covariates. Results: Three out of the eight evaluated LTL SNPs were significantly associated with increased meningioma risk (rs10936599: OR 1.14, 95% CI 1.01–1.28, rs2736100: OR 1.13, 95% CI 1.03–1.25, rs9420907: OR 1.22, 95% CI 1.07–1.39). Only rs9420907 remained significant after correction for multiple testing. Average genotypically-estimated LTL was significantly longer for those with meningioma compared to controls [mean cases: 560.2 bp (standard error (SE): 4.05 bp), mean controls: 541.5 bp (SE: 2.02 bp), logistic regression p value = 2.13 × 10−5]. Conclusion: Increased genotypically-estimated LTL was significantly associated with increased meningioma risk. A role for telomere length in the pathophysiology of meningioma is novel, and could lead to new insights on the etiology of meningioma. [ABSTRACT FROM AUTHOR]

Leukocyte telomere length (LTL) is a biomarker of cellular aging. African Americans report more stress than other groups; however, the association of psychosocial stressors with biological aging among African Americans remains unclear. The current study evaluated the association of psychosocial factors (negative affect and stressors) with LTL in a large sample of African American men and women (n = 2,516) from the Jackson Heart Study. Using multivariable linear regression, we examined the sex‐specific associations of psychosocial factors (cynical distrust, anger in and out, depressive symptoms, negative affect summary scores, global stress, weekly stress, major life events, and stress summary scores) with LTL. Model 1 adjusted for demographics and education. Model 2 adjusted for model 1, smoking, alcohol intake, physical activity, diabetes, hypertension, and high‐sensitivity C‐reactive protein. Among women, high (vs. low) cynical distrust was associated with shorter mean LTL in model 1 (b = −0.12; p = 0.039). Additionally, high (vs. low) anger out and expressed negative affect summary scores were associated with shorter LTL among women after full adjustment (b = −0.13; p = 0.011; b = −0.12, p = 0.031, respectively). High levels of cynical distrust, anger out, and negative affect summary scores may be risk factors for shorter LTL, particularly among African‐American women. [ABSTRACT FROM AUTHOR]

Objectives: The increased cardiovascular risk seen in patients with obstructive sleep apnea (OSA) may be due to combination of oxidative stress, systemic inflammation and damage to leukocyte telomere length (LTL) seen with aging. Another molecule, Sirtuin 1 (SIRT1), a histone/protein deacetylase, regulates endothelial nitric oxide synthase and is involved in different aspects of cardiovascular disease, aging and stress resistance. The aim of this study was to evaluate the effects of mandibular advancement device (MAD) on the circulating LTL and SIRT1 protein level in peripheral blood mononuclear cells (PBMCs) in patients with OSA. Materials and methods: Forty patients with moderately severe to severe OSA who desired MAD and 20 healthy controls were prospectively enrolled. The LTL was measured by quantitative polymerase chain reaction while SIRT1 protein levels in PBMC was assessed using a Sirtuin 1 ELISA Kit. All study subjects underwent baseline sleep study, with OSA patients having repeat testing at 3 months after MAD. Results: Compared to healthy subjects, patients with OSA at baseline had lower LTL and SIRT1 protein levels in PBMC. After 3 months of MAD, 24 OSA patients, designated as MAD responders, median (range) LTL increased from (0.556 [0.393–0.748]) to (0.708 [0.533–0.893]) and SIRT1 protein levels in PBMC increased from 0.58 ± 0.23 pg/μg of total protein to 0.95 ± 0.26 pg/μg of total protein. For the 16 MAD unresponsive patients, LTL and SIRT1 protein levels remained low. Conclusions: Successful treatment of OSA with MAD can restore LTL and SIRT1 protein levels in PBMC. Clinical relevance: LTL and SIRT1 protein levels in PBMC can be improved following effective treatment of OSA using MAD. [ABSTRACT FROM AUTHOR]

Highlights • Caregiving for a child with an autism spectrum disorder (ASD) is a chronic stressor. • How caregivers integrate stressful experiences is correlated with mental and psychobiological health outcomes. • Caregivers with more integrated narratives had slower telomere shortening over 18 months. • Narrative integration, not affective themes, correlated with positive biological indicators. • Integrating what caregiving means for self-identity may be a source of stress resilience. Abstract Background Chronic caregiving stress may accelerate biological aging; however, the ability to integrate the meaning of caregiving through self-awareness, adaptation, and growth can buffer the negative effects of stress. Narrative researchers have shown that people who coherently integrate difficult experiences into their life story tend to have better mental health, but no prior study has examined the prospective association between narrative identity and biological indicators, such as telomere length. We tested whether narrative identity might be prospectively associated with resilience to long-term parenting stress, depressive symptoms, and protection from telomere shortening, especially among caregivers. Methods We conducted a semi-structured interview about parenting and quantified narrative themes by applying well-validated, standardized coding systems with high inter-rater reliability among 88 mothers: 32 "caregivers" (mothers with a child diagnosed with an autism spectrum disorder), and 56 "controls" (mothers with a neurotypical child). To assess longitudinal changes, we measured mental health (parenting stress [PS], depressive symptoms [DS]) and leukocyte telomere length [LTL], a biomarker of aging, at baseline and again 18 months later. We examined whether narrative identity themes were related to these outcomes and whether associations differed across caregivers versus controls. Results Caregivers exhibited significantly higher basal levels of PS and DS relative to controls (all p's <.05), but no significant difference in LTL (p >.05). Caregivers rated higher in the narrative theme of integration showed healthier future 18-month trajectories in PS (B = −0.832, 99% CI: [−1.315, −0.155], p <.01) and LTL (B = 1.193, 99% CI: [0.526, 2.130], p <.01), but no differences in depressive symptoms (p >.05), adjusting for age and antidepressant use. Analyses examining affective themes in caregiver narratives did not demonstrate significant associations. Narrative themes did not predict outcomes in controls. Conclusions The data suggest that narratives reflecting coherent integration, but not necessarily affect, prospectively relate to psychological and biological stress resilience. Maternal caregivers' ability to tell an integrated story of their parenting experiences forecasts lower parenting stress and telomere shortening over time. This study suggests the possibility that helping individuals better integrate the meaning of stressful experiences, but not necessarily to affectively redeem them, may constitute a potential novel target for intervention among chronically stressed populations such as caregivers. [ABSTRACT FROM AUTHOR]

Abstract Internet gaming addiction (IGA) has been associated with many negative health outcomes, especially for youth. In particular, the potential association between IGA and leukocyte telomere length (LTL) has yet to be examined. In this study we compared LTL in Korean male adolescents with and without IGA and examined the association between LTL and autonomic functions. Specifically, plasma catecholamine, serum cortisol, and psychological stress levels were measured as autonomic functions. Data were collected using participant blood samples analyzed for LTL, catecholamine, and cortisol levels and a set of questionnaires to assess IGA and psychological stress levels of the participants. The LTL measurements were made using a qPCR-based technique, and the relative LTL was calculated as the telomere/single copy (T/S) ratio. T/S ratio was significantly shorter in the IGA group than in the non-IGA group (150.43 ± 6.20 and 187.23 ± 6.42, respectively; p <.001) after adjusting for age. In a univariate regression analysis, age, daily Internet gaming time, IGA score, and catecholamine level (epinephrine and norepinephrine) were significantly associated with T/S ratio. However, duration of Internet gaming exposure, dopamine, cortisol, and psychological stress levels were not found to be associated with T/S ratio. In the final multiple linear regression model, age, daily Internet gaming time, and epinephrine level showed statistically significant relationships with T/S ratio. Our results indicate that in addition to age, involvement in excessive Internet gaming may induce LTL shortening in male adolescents, which may be partially attributable to changes in autonomic function such as catecholamine level. These findings further understanding of the health effects of IGA and highlight the need for screening and intervention strategies for male adolescents with IGA. Highlights • Internet gaming addiction (IGA) can induce various changes in physiological states. • Plasma epinephrine level differs significantly between the IGA and non-IGA groups. • Male adolescents with IGA have shorter telomere length than those without. • Internet gaming time, epinephrine, and age are associated with telomere shortening. [ABSTRACT FROM AUTHOR]

Abstract Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by an expanded CAG repeat. Though symptom onset commonly occurs at midlife and inversely correlates with the CAG repeat expansion, age at clinical onset and progression rate are variable. In the present study we investigated the relationship between leukocyte telomere length (LTL) and HD development. LTL was measured by real-time PCR in manifest HD patients (HD, n = 62), pre-manifest HD patients (pre-HD, n = 38), and age-matched controls (n = 76). Significant LTL differences were observed between the three groups (p <.0001), with LTL values in the order: HD < pre-HD < controls. The relationship between LTL and age was different in the three groups. An inverse relationship between mean LTL and CAG repeat number was found in the pre-HD (p =.03). The overall data seem to indicate that after age 30 years, LT begins to shorten markedly in pre-HD patients according to CAG number and increasing age, up to the values observed in HD. This very suggestive picture allowed us to hypothesize that in pre-manifest HD, LTL could be a measure of time to clinical HD onset. The possible use of LTL as a reliable biomarker to track HD development and progression was evaluated and discussed. Highlights • LTL was measured in controls, pre-manifest and manifest HD patients. • LTL was higher in controls, intermediate in pre-manifest HD, lower in HD patients. • The decreasing trend of LTL with age differed between the three groups. • LTL shortening in pre-manifest HD depends on advancing age and CAG number. • LTL could be a valid and accurate biomarker to track HD development. [ABSTRACT FROM AUTHOR]

Rates of aging vary markedly among individuals, and biological age serves as a more reliable predictor of current health status than does chronological age. As such, the ability to predict biological age can support appropriate and timely active interventions aimed at improving coping with the aging process. However, the aging process is highly complex and multifactorial. Therefore, it is more scientific to construct a prediction model for biological age from multiple dimensions systematically. Physiological and biochemical parameters were evaluated to gage individual health status. Then, age-related indices were screened for inclusion in a model capable of predicting biological age. For subsequent modeling analyses, samples were divided into training and validation sets for subsequent deep learning model-based analyses (e.g. linear regression, lasso model, ridge regression, bayesian ridge regression, elasticity network, k-nearest neighbor, linear support vector machine, support vector machine, and decision tree models, and so on), with the model exhibiting the best ability to predict biological age thereby being identified. First, we defined the individual biological age according to the individual health status. Then, after 22 candidate indices (DNA methylation, leukocyte telomere length, and specific physiological and biochemical indicators) were screened for inclusion in a model capable of predicting biological age, 14 age-related indices and gender were used to construct a model via the Bagged Trees method, which was found to be the most reliable qualitative prediction model for biological age (accuracy=75.6%, AUC=0.84) by comparing 30 different classification algorithm models. The most reliable quantitative predictive model for biological age was found to be the model developed using the Rational Quadratic method (R2=0.85, RMSE=8.731 years) by comparing 24 regression algorithm models. Both qualitative model and quantitative model of biological age were successfully constructed from a multi-dimensional and systematic perspective. The predictive performance of our models was similar in both smaller and larger datasets, making it well-suited to predicting a given individual's biological age. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Exercise and consumption of green tea affect the aging process. However, the effect of exercise training combined with green tea extract on leukocyte telomere length, quality of life (QoL) and body composition in aging has so far been unclear and inconsistent. Objective: The aim of the present study was to determine the effectiveness of aerobic training intervention and green tea extracts consumption either alone or in combination on leukocyte telomere length, QoL and body composition among elderly women. Methods: Thirty six elderly women, 60–65 years, were randomly divided into two groups, the exercise alone (placebo group) and exercise with green tea consumption (green tea group). All participants in both groups were engaged to aerobic protocol exercise three times in week for five months. The participants in green tea group received green tea extract capsule 500 mg and placebo group received toasted powder capsule 500 mg three times a day for a period of five months. At baseline and end of the study the leukocyte telomere length, QoL and body composition were measured. Results: There were significant increase on leukocyte telomere length in green tea group compared with the baseline (P=0.004) and also placebo group (P=0.041) at the end of the study. Waist–hip ratio was also significantly decreased in green tea group compared with placebo group (P=0.016). Conclusion: Our findings shows that combination of aerobic training with consumption of green tea has synergic effect on waist–hip ratio and leukocyte telomere length associated with aging among elderly women.

Polychlorinated biphenyls (PCBs) induce the expression of the proto-oncogene c-myc which has a role in cellular growth and proliferation programs. The c-myc up-regulates the telomerase reverse transcriptase which adds the telomeres repeating sequences to the chromosomal ends to compensate for the progressive loss of telomeric sequence. We performed multivariate linear regression to analyze the association of PCBs, polychlorinated dibenzo-p-dioxins, and 1,2,3,4,6,7,8-heptachlorodibenzofuran with leukocyte telomere length (LTL) in the adult population (n = 2413) of the National Health and Nutrition Examination Survey 1999–2002. LTL was natural log-transformed and the results were re-transformed and presented as percent differences. Individuals in the 3rd and 4th quartiles of the sum of PCBs were associated with 8.33% (95% CI: 4.08–13.88) and 11.63% (95% CI: 6.18–17.35) longer LTLs, respectively, compared with the lowest quartile, with evidence of a dose–response relationship (p-trend

Background: Endometriosis (EMs) is a common gynecological disorder. Observational studies on the relationship between leukocyte telomere length (LTL) and EMs have shown conflicting results. The purpose of this study was to evaluate the precise causal relationship between LTL and EMs using Mendelian randomization (MR) methodology., Methods: We employed MR to assess the causal relationship between LTL and EMs. Summary data from several large-scale genome-wide association studies (GWAS) were used for bidirectional two-sample MR analysis. Sensitivity analyses were conducted to ensure the robustness of our results. All analyses were also replicated in another completely independent EMs dataset., Results: Our MR analysis indicated that genetically predicted longer LTL increased the risk of EMs (IVW: discovery, OR=1.169, 95%CI: 1.059-1.290, p=0.002; validation, OR=1.302, 95%CI: 1.140-1.487, p=0.000), while EMs had no causal impact on LTL (IVW: discovery, OR=1.013, 95%CI: 1.000-1.027, p=0.056; IVW: validation, OR=1.005, 95%CI: 0.995-1.015, p=0.363). Causal estimates were supported by various calculation models (including MR-Egger, Weighted median, MR-PRESSO, and MR-RAPS). Heterogeneity and pleiotropy analyses also indicated robustness of the results., Conclusion: Our findings substantiate the idea that a genetically predicted longer LTL elevates the risk of EMs, with no influence of EMs on LTL risk. This research bolsters the causal link between LTL and EMs, overcoming the constraints of earlier observational studies. It implies that LTL may potentially function as a biomarker for EMs, opening up novel possibilities for EMs prevention and treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bai, Shen, Qiu and Zhang.)

Objective: To examine the association between depressive symptoms, leukocyte telomere length-a marker of cellular ageing, and survival amongst lung cancer patients., Design: Patients with non-small cell lung cancer were recruited from a university-affiliated cancer center clinic., Main Outcome: Patients ( N  = 67) reported on depressive symptoms and provided a blood sample for leukocyte telomere length assessment at baseline and at a 3-month follow-up. Survival status was tracked over 3 years., Results: Age at diagnosis and depressive symptoms, as measured by the CES-D, were associated with shorter leukocyte telomere length ( p < .05), although only age at diagnosis contributed statistical significance to the model. Depressive symptoms predicted shorter survival from date of diagnosis ( p < .01). Patients who reported experiencing clinically meaningful levels of depressive symptoms (CES-D scores ≥ 16) demonstrated shorter survival than those who reported sub-clinical levels of depressive symptoms ( p < .05). Leukocyte telomere length did not emerge as a predictor of shorter survival., Conclusion: Clinically meaningful levels of depressive symptoms are associated with shorter survival amongst lung cancer patients. These findings support the on-going efforts to screen all cancer patients for low mood and to investigate mechanisms linking depressive symptoms and shorter survival in cancer contexts.

Background: Childhood maltreatment can result in lifelong psychological and physical sequelae, including coronary artery disease (CAD). Mechanisms leading to increased risk of illness may involve emotional dysregulation and shortened leukocyte telomere length (LTL)., Methods: To evaluate whether (1) childhood maltreatment is associated with shorter LTL among older adults with CAD or other chronic illnesses; (2) sex and/or CAD status influence these results; and (3) symptoms of anxiety, depression, and stress moderate or mediate the association between childhood maltreatment and LTL, men and women ( N = 1247; aged 65 ± 7.2 years) with and without CAD completed validated questionnaires on childhood maltreatment, symptoms of depression, anxiety, and perceived stress. LTL was measured using quantitative polymerase chain reaction. Analyses included bivariate correlations, hierarchical regressions, and moderation/mediation analyses, controlling for sociodemographic and lifestyle variables., Results: Childhood maltreatment was associated with significantly shorter LTL ( r = -0.059, p = 0.038, b = -0.016, p = 0.005). This relation was not moderated by depression, anxiety, nor perceived stress, though there was mitigated evidence for absence of a maltreatment-LTL relation in men with CAD. Stress perception (but not anxiety or depression) partially mediated the relation between childhood maltreatment and LTL [Indirect effect, b = -0.0041, s.e. = 0.002, 95% CI (-0.0085 to -0.0002)]., Conclusions: Childhood maltreatment was associated with accelerated biological aging independently of patient characteristics. Emotional dysregulation resulting in chronic stress may contribute to this process. Whether stress management or other interventions may help prevent or slow premature aging in those who have suffered maltreatment requires study.

Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of inflammation and oxidative stress in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension and investigated whether inflammation and oxidative stress played a mediating role in this relationship. Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint (albuminuria progression and rapid decline in renal function). Logistic regression and simple mediation models were used for the analysis. Results: In this cohort (mean age, 54.3±9.7 years; follow-up period, 5.9±1.1 years), 42(16.0%), 21(8.0%), and 59(22.5%) patients developed albuminuria progression, rapid eGFR decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease of baseline LTL and the lower quartile (Q) of baseline LTL were significantly correlated with an increased risk of rapid decline in renal function (OR=1.83 [95% CI 1.07, 3.27] per 1SD, P =0.03; OR=7.57 [95% CI 1.25, 145.88] for Q1 vs. Q4, P for trend=0.031); and the composite endpoint of kidney dysfunction (OR=1.37 [95% CI 0.97, 1.96] per 1SD, borderline positive P =0.072; OR=2.96[95% CI 1.15, 8.2] for Q1 vs. Q4, P for trend=0.036). The mediating analysis showed that tumor necrosis factor (TNF)-a partly mediated the relationship between LTL and rapid decline in renal function (direct effect: β=0.046 95%CI [0.006, 0.090],P=0.02; indirect effect: β=0.013 95%CI [0.003, 0.020]), and the mediating proportion was 22.4%.In subgroup analyses, LTL was inversely associated with rapid decline in renal function or the composite endpoint of kidney dysfunction only in patients with hypertension (OR=49.07[3.72,211.12] vs. 1.32[0.69,2.58] per 1SD, P for interaction=0.045;OR=3.10 [1.48, 7.52] vs. 1.08[0.92,1.63] per 1SD, P for interaction=0.036). Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-a partially mediated the negative association between LTL and kidney dysfunction., Competing Interests: Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (© The author(s).)

Objectives: Telomeres are DNA-protein complexes at the ends of linear chromosomes that protect against DNA degradation. Telomeres shorten during normal cell divisions and therefore, telomere length is an indicator of mitotic-cell age. In humans, telomere shortening is a potential biomarker for disease risk, progression and premature death. Physical activity has been associated with longer leukocyte telomere length (LTL) in some studies. In the current study the relationship between LTL, thigh muscle mass and adipose tissue distribution was explored., Methods: We performed anthropometric measurements and magnetic resonance imaging (MRI) measurements of the thigh in 149 healthy subjects (77 male, 72 female). LTL was measured using qPCR. Additionally, the subjects answered a questionnaire concerning their training behaviour., Results: In male subjects, LTL was significantly associated with thigh muscle mass, independent of age and body mass index (p=0.006). In addition, a slight association of LTL with weekly endurance units in the male group was found. These relations could not be observed in females., Conclusions: In conclusion, we observed a sex-specific association of LTL and thigh muscle mass in healthy males. The reason of this sex-specific association is currently unclear, but could be related to different training effects and/or hormonal pathways in men and women., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Objective: Some epidemiological studies have investigated the associations between aging and constipation, yet their outcomes are inconclusive, so we strive to ascertain whether aging is the cause of constipation., Methods: We conducted a two-sample Mendelian randomization (MR) analysis using publicly accessible genome-wide association study (GWAS) summary statistics. As a marker of cellular and biological aging, we employed 15 single-nucleotide polymorphisms as instrumental variables for leukocyte telomere length (LTL) as exposure and a GWAS for constipation in the Finnish database as an outcome. To select the instrumental variables strongly associated with the phenotype, we eliminated confounding factors and direct effects outcomes to determine the causal relationship of exposure factors on the outcome; the analysis was mainly performed using the random-effect inverse variance weighting method, MR-Egger, weighted median, and sensitivity analysis of the results., Results: Random effect inverse variance weighted odds ratio = 1.035 (95% CI 0.907-1.180), but p = 0.612, which was not statistically significant. Other statistical methods, such as MR-Egger and weighted median, also yielded non-significant results., Conclusion: LTL as a proxy for aging does not necessarily indicate an increased likelihood of constipation. Further research is needed to explore the specific mechanisms of constipation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chi, Bai and Zhang.)

Aging is the biggest risk factor for the development of chronic diseases. Telomere length may represent one important mechanism by which dietary intake influences risk of age-related diseases; however, it is unknown which diet pattern is most strongly related to telomere length. We compared the relationships between 4 evidence-based diet quality indices and leukocyte telomere length in a nationally representative sample of healthy adults, and the extent to which these associations differed between men and women. Data on 4,758 adults aged 20–65 years with no prior diagnosis of major chronic disease were obtained from the 1999–2002 cycles of the National Health and Nutrition Examination Survey. Diet was assessed using one 24-hour dietary recall. After adjustment for sociodemographic and health characteristics, comparison of the top and bottom quintiles showed that higher Healthy Eating Index 2010 scores (β = 0.065, 95% confidence interval (CI): 0.018, 0.112; P -trend = 0.007), Alternate Healthy Eating Index 2010 scores (β = 0.054, 95% CI: 0.010, 0.097; P -trend = 0.007), Mediterranean Diet scores (β = 0.058, 95% CI: 0.017, 0.098; P -trend = 0.008), and Dietary Approaches to Stop Hypertension (DASH) scores (β = 0.052, 95% CI: 0.014, 0.090; P -trend = 0.007) were each associated with longer telomere length in women. These results may provide insight into the complex associations between optimal nutrition and longevity. Further investigation is needed to understand why associations were not observed in men. [ABSTRACT FROM AUTHOR]

Background Endocrine-disrupting chemicals (EDCs) can target immune and metabolic pathways. However, few epidemiologic studies have examined the influence of EDCs on measures of inflammation and cellular aging during pregnancy and postpartum. Objective We investigated associations between prenatal exposures to polybrominated diphenyl ethers (PBDEs), hydroxylated PBDE metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and per- and polyfluorochemicals (PFASs) with repeated biomarker measurements of inflammation and cellular aging in women during pregnancy and the postpartum period. Methodology Overweight or obese pregnant women were recruited from the San Francisco Bay area (n = 103) during their first or second trimester of pregnancy. Blood samples were collected from participants at baseline (median 16 weeks gestation) and at three and nine months postpartum. Serum concentrations of PBDEs, OH-PBDEs, PCBs, and PFASs were measured at baseline. Inflammation biomarkers (interleukin 6 [IL-6], interleukin 10 [IL-10], and tumor necrosis factor [TNF-α]) and leukocyte telomere length (LTL), a biomarker of cellular aging, were measured at all three time points. Associations between serum chemical concentrations and repeated measures of IL-6, IL-10, TNF-α, and LTL were examined using linear mixed models. We also examined the potential for effect modification by time (visit) and obesity. Results In adjusted models, we observed positive relationships between PBDEs and pro-inflammatory cytokines (IL-6 and TNF-α). A doubling in ∑PBDEs was associated with a 15.26% (95% CI 1.24, 31.22) and 3.74% (95% CI −0.19, 7.82) increase in IL-6 and TNF-α, respectively. Positive associations were also observed for PFASs and IL-6. A two-fold increase in ∑PFASs was associated with a 20.87% (95% CI 3.46, 41.22) increase in IL-6. 5-OHBDE-47 was inversely associated with anti-inflammatory cytokine IL-10. Some EDC-outcome associations, including those of PBDEs with TNF-α, were stronger during pregnancy (compared to three or nine months postpartum) and among obese (compared to overweight) women (p-interaction <0.05). Conclusions These findings suggest that exposure to specific EDCs is associated with increased inflammation among women during pregnancy and the postpartum period. Future studies should replicate these findings in additional study populations and examine the implications of these associations for maternal and child health. [ABSTRACT FROM AUTHOR]

The survival of patients undergoing hematopoietic cell transplantation (HCT) from unrelated donors for acute leukemia exhibits considerable variation, even after stringent genetic matching. To improve the donor selection process, we attempted to create an algorithm to quantify the likelihood of survival to 5 years after unrelated donor HCT for acute leukemia, based on the clinical characteristics of the donor selected. All standard clinical variables were included in the model, which also included average leukocyte telomere length of the donor based on its association with recipient survival in severe aplastic anemia, and links to multiple malignancies. We developed a multivariate classifier that assigned a Preferred or NotPreferred label to each prospective donor based on the survival of the recipient. In a previous analysis using a resampling method, recipients with donors labeled Preferred experienced clinically compelling better survival compared with those labeled NotPreferred by the test. However, in a pivotal validation study in an independent cohort of 522 patients, the overall survival of the Preferred and NotPreferred donor groups was not significantly different. Although machine learning approaches have successfully modeled other biological phenomena and have led to accurate predictive models, our attempt to predict HCT outcomes after unrelated donor transplantation was not successful. [ABSTRACT FROM AUTHOR]

Backgrounds: Accelerated cellular ageing, which can be examined by telomere length (TL), may be an overarching mechanism underlying the association between personality and adverse health outcomes. This 6-year longitudinal study examined the relation between personality and leukocyte telomere length (LTL) across time among adults with a wide age-range. Methods: Data from the Netherlands Study of Depression and Anxiety were used and included patients with a depression and/or anxiety disorder and healthy controls. Overall, 2936 persons (18–65 years, 66% female) had data on LTL at baseline and 1883 persons had LTL at 6-year follow-up. The Big Five personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) and Type D personality were assessed. Results: Neuroticism was negatively (B = −2.11, p = 0.03) and agreeableness was positively (B = 3.84, p = 0.03) related to LTL measured across two time points, which became just non-significant after adjusting for somatic health, lifestyle factors, and recent life stress (B = −1.99, p = 0.06; and B = 3.01, p = 0.10). Type D personality was negatively (B = −50.16, p < 0.01) related to LTL across two time points, which still remained statistically significant after full adjustment (B = −47.37, p = 0.01). Associations did not differ by age, gender, and current psychiatric status. Conclusions: The Big Five traits high neuroticism and low agreeableness, and Type D personality were associated with shorter LTL measured across a 6-year period. Associations with the Big Five traits became non-significant after controlling for somatic health, lifestyle factors, and recent life stress, yet similar trends were observed. Type D personality remained independently associated with shorter LTL after full adjustment. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to determine the potential role of leukocyte telomere length as a biomarker for development of childhood obesity in a low‐income Latino population. A birth cohort of Latino children (N = 201) in San Francisco (recruited May 2006–May 2007) was followed until age 9 and assessed annually for obesity and dietary intake. Leukocyte telomere length was measured at 4 and 5 years (n = 102) and assessed as a predictor for obesity at age 9, adjusting for known risk factors. Furthermore, leukocyte telomere length at age 4 and 5 was evaluated as a possible mediator of the relationship between excessive sugar‐sweetened beverage consumption and obesity at age 9. Shorter leukocyte telomere length in preschoolers was associated with obesity at age 9 (adjusted odds ratio 0.35, 95% confidence interval 0.13–0.94) after adjustment for known risk factors. Telomere length mediated 11% of the relationship between excessive sugar‐sweetened beverage consumption and obesity. Shorter leukocyte telomere length may be an indicator of future obesity risk in high‐risk populations as it is particularly sensitive to damage from oxidative stress exposure, including those from sugar‐sweetened beverages. [ABSTRACT FROM AUTHOR]

Evidence has shown that leukocyte telomere length (LTL) at birth is related to the susceptibility to various diseases in later life and the setting of newborn LTL is influenced by the intrauterine environment. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a kind of persistent organic pollutants, are commonly used in commercial and domestic applications and are capable of crossing the maternal-fetal barrier during pregnancy. We hypothesized that intrauterine exposure to PFASs may affect fetal LTL by increasing oxidative stress. To verify this hypothesis, LTL, concentrations of PFASs and reactive oxygen species (ROS) were measured in umbilical cord blood of 581 newborns from a prospective cohort. Our results showed that there were interactions between PFOS/PFDA and sex on LTL and ROS. The LTL was significantly shorter (0.926 ± 0.053 vs 0.945 ± 0.054, P  = .023 for PFOS; 0.919 ± 0.063 vs 0.940 ± 0.059, P  = .011 for PFDA) and the ROS levels were extremely higher (252.9 ± 60.5 [M] vs 233.5 ± 53.6 [M], P  = .031 for PFOS; 255.2 ± 62.9 [M] vs 232.9 ± 58.3 [M], P  = .011 for PFDA) in the female newborns whose PFOS or PFDA concentrations fell in the upmost quartile compared with those in the lowest quartile after adjusting for potential confounders. ROS levels were inversely associated with LTL in female newborns ( β  = −1.42 × 10 −4 , P  = .022). 13% of the effect of PFOS on female LTL was mediated through ROS approximately by the mediation analyses. However, in male newborns, no relationships among PFASs, ROS and LTL were observed. Our findings suggest a “programming” role of PFASs on fetal telomere biology system in females in intrauterine stage. [ABSTRACT FROM AUTHOR]

Background: Maternal combination antiretroviral therapy (cART) during pregnancy could impact the health of human immunodeficiency virus (HIV)-exposed, HIV-uninfected (HEU) children, because some antiretrovirals cross the placenta and can inhibit telomerase. Our objective was to compare leukocyte telomere length (LTL) in HEU children and HIV-unexposed, HIV-uninfected (HUU) children at birth and in early life and to investigate any relationship with cART exposure.Methods: HEU and HUU children's blood LTL was compared cross-sectionally at birth, and during the first three years of life. Longitudinal HEU LTL dynamics was evaluated over that same period.Results: At birth, the LTL in HEU children (n = 114) was not shorter than that in HUU children (n = 86), but female infants had longer LTL than male infants. Maternal cART (duration or type) showed no association with shorter infant LTL. Among 214 HEU children age- and sex-matched at a 1:1 ratio to HUU children, LTL declined similarly in both groups. In a longitudinal analysis, LTL attrition in HEU children was rapid from birth to 1 year of age and gradual thereafter. Zidovudine prophylaxis did not significantly alter LTL.Conclusions: Our results indicate that from birth to 3 years of age, the LTL in HEU children is not negatively affected by exposure to maternal HIV infection and cART, at least not to the regimens used within this Canadian cohort, a reassuring finding. [ABSTRACT FROM AUTHOR]

Aims: We investigated leukocyte relative telomere length (TL) in patients with type 2 diabetes (T2D) diagnosed for no longer than five years and its association with clinical and biochemical variables.Methods: Peripheral blood leukocyte relative TL was investigated in 108 patients with T2D (87 women, 21 men) and 125 (37 women, 88 men) age-matched control subjects with normal glucose tolerance, by quantitative polymerase chain reaction. Multiple linear regression analysis was used to examine the association between relative TL and demographic, anthropometric and biochemical indicators of metabolic control among patients with T2D.Results: Patients with T2D had a median time since diagnosis of 1 year and most were on metformin monotherapy, with satisfactory glucose control determined by HbA1c levels. Median relative TL was not different between patients with T2D and control subjects. However, multiple linear regression analyses showed that relative TL was inversely associated with time since T2D diagnosis, fasting plasma glucose levels and HbA1c levels, but not with HbA1c levels assessed in the preceding 5-12 months, after adjustment for age, sex and body mass index.Conclusion: This study suggests that relative TL is not shorter in patients with recently diagnosed T2D, but is inversely correlated with glucose levels, even among patients with overall satisfactory glucose control. [ABSTRACT FROM AUTHOR]