Difference In Leukocyte Telomere Length Research Articles

125 RATE OF TELOMERE SHORTENING AND CARDIOVASCULAR PHENOTYPES

IntroductionCross-sectional adult studies report associations between short leukocyte telomere length (LTL) and measures of vascular and cardiac damage. However, due to high inter-individual differences in LTL at birth and thereafter,...

Socioeconomic factors and leukocyte telomere length in a multi-ethnic sample: findings from the multi-ethnic study of atherosclerosis (MESA).

Previous findings have linked lower socioeconomic status (SES) with elevated morbidity and mortality. Leukocyte telomere length (LTL), which also has been associated with age-related disease morbidity and mortality, is a marker of aging at the cellular level, making it a valuable early biomarker of risk and an indicator of biological age. It is hypothesized that SES will be associated with LTL, indicating that SES influences disease risk by accelerating biological aging. In the present sample we test for associations of childhood SES and adult SES (i.e. education, income, home ownership) with LTL, and examine whether these associations vary by racial/ethnic group. Analyses on 963 subjects (18.7% White, 53% Hispanics, and 28.5% African American) from the stress ancillary study of the multi-ethnic study of atherosclerosis revealed a significant difference in LTL between home owners and renters in Hispanic and White participants (p<.05), but not amongst African Americans (p=.98). There were no linear associations of adult education or family income with LTL, however, there was an inverse association between father's education and LTL (p=.03). These findings suggest that for Whites and Hispanics renting vs. owning a home is associated with an older biological age; however we did not replicate previous findings linking education with LTL.

Functional Haplotypes of the hTERT Gene, Leukocyte Telomere Length Shortening, and the Risk of Peripheral Arterial Disease

BackgroundThe development of peripheral arterial disease (PAD) is heterogeneous even in the presence of similar risk factors. Our aim was to determine whether inter-individual differences in leukocyte telomere length contribute to the susceptibility of PAD.MethodsA total of 485 patients with PAD (defined by the ankle-brachial index) and 970 age- and gender-matched controls were recruited from seven rural communities in Henan Province in China. The relative leukocyte telomere length was determined by a quantitative PCR-based method. Two common promoter variants of the hTERT gene were genotyped to assess their effects on telomere length and the risk of PAD. In vivo luciferase assay was performed to study the transcriptional activity.ResultsAfter adjustment for vascular risk factors and genetic variants in the hTERT gene, individuals in the lowest and middle tertiles of telomere length had a significantly higher risk of PAD than did those in the highest tertile (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.29–2.49 in the middle tertile; 3.15, 95%CI 2.31–4.29 in the lowest tertile). Haplotype analysis using the 2 variants (rs2735940 and rs2853669) showed that subjects with the at-risk C-C haplotype had shorter telomere length than those individuals with the T-T haplotype and consistently had 1.30-fold (OR 1.30, 95%CI 1.06–1.58; P = 0.005) increased risk for PAD. The C-C haplotype had 43% lowered transcription activity of hTERT promoter (P<0.001).ConclusionThe associations between the functional haplotype of hTERT gene and telomere length and the risk of atherosclerotic PAD suggested that mean leukocyte telomere length may independently serve as a potential predictor of PAD.

Leukocyte telomere length and physical ability among Danish Twins age 70+

Leukocyte telomere length (LTL) shortens with age and is potentially a biomarker of human aging.We examined the relation of LTL with physical ability and cognitive function in 548 same-sex twins from the Longitudinal Study of Aging Danish Twins. LTL was measured by Southern blots of the terminal restriction fragments (TRF). Physical ability was evaluated using a self reported scale of 11 questions, while cognitive function was scored by MMSE and a cognitive composite score sensitive to age-related decline.A random intercept model revealed a positive, significant association between LTL and physical ability. For every unit increase in physical ability score, LTL increased by 0.066kb (p=0.01), equal to approximately three years of age-dependent LTL shortening. A matched case-co-twin design showed that the group consisting of the twins from each pair with the longer LTL also displayed better physical ability (p<0.01). Moreover, the intra-pair difference in LTL was associated with intra-pair difference in physical ability (p<0.01), confirming the association. However, we found no association between cognitive function and LTL.The LTL-physical ability association in the elderly provides further support to the premise that LTL is an index of somatic fitness in the narrow context of human physical health.

Childhood Trauma Associated with Short Leukocyte Telomere Length in Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is associated with increased risk for age-related diseases and early mortality. An accelerated rate of biological aging could contribute to this increased risk. To investigate, we assessed leukocyte telomere length (LTL), an emerging marker of biological age, in men and women with and without PTSD. We also examined childhood trauma, a risk factor for both PTSD and short LTL, as a potential contributor to short LTL in PTSD. Participants included 43 adults with chronic PTSD (n = 18 with multiple categories of childhood trauma) and 47 control subjects (none with multiple categories of childhood trauma) (mean age = 30.55, SD = 7.44). Exclusion criteria included physical illness, medication use, obesity, alcohol or substance abuse, and pregnancy. Structured clinical interviews were conducted to assess PTSD and other psychiatric disorders and childhood trauma exposure. LTL was measured with a quantitative polymerase chain reaction method. As predicted, participants with PTSD had shorter age-adjusted LTL than control subjects. Exposure to childhood trauma was also associated with short LTL. In fact, childhood trauma seemed to account for the PTSD group difference in LTL; only participants with PTSD and exposure to multiple categories of childhood trauma had significantly shorter LTL than control subjects. Childhood trauma is associated with short LTL in individuals with PTSD. Chronic exposure to the psychobiological sequelae of childhood trauma could increase risk for PTSD and short LTL. Thus, the lasting psychological impact of exposure to trauma in childhood might be accompanied by equally enduring changes at the molecular level.

Longitudinal versus Cross-sectional Evaluations of Leukocyte Telomere Length Dynamics: Age-Dependent Telomere Shortening is the Rule

Background.Leukocyte telomere length (LTL) is considered a biomarker of human aging and based on cross-sectional studies it shortens with age. However, longitudinal studies reported that many adults display LTL lengthening.Methods.Using Southern blots, we compared cross-sectional rates of age-related LTL change across a ∼20 year age range with those based on longitudinal evaluations in three surveys (S1, S2, and S3) with three time intervals: S1–S2 (5.8 years), S2–S3 (6.6 years), and S1–S3 (12.4 years). Hierarchical linear modeling was used to explore LTL dynamics using LTL data from S1, S2, and S3.Results.Cross-sectionally, mean LTL shortenings were 24.6, 25.4, and 23.6 bp/y at S1, S2, and S3, respectively. Longitudinally, more variation was observed in the rate of LTL change during the shorter than longer follow-up periods. Furthermore, using simple differences in LTL, 14.4% and 10.7% of individuals displayed LTL lengthening during S1–S2 and S2–S3, respectively, but only 1.5% during S1–S3 (p < 0.001). The estimated mean rate of LTL shortening based on averaging empirical Bayes’ estimates of LTL from a parsimonious hierarchical linear modeling model was 31 bp/y with a range from 23 to 47 bp/y with none of the participants showing LTL lengthening over the average 12.4 years of follow-up.Conclusions.As aging displays a unidirectional progression, it is unlikely that LTL elongates with age. LTL elongation in longitudinal studies primarily reflects measurement errors of LTL in relation to the duration of follow-up periods.

Leukocyte Telomere Length Is Associated with Disability in Older U.S. Population

To determine whether mean leukocyte telomere length (LTL) serves as a biomarker of disability assessed according to activities of daily living (ADLs) and what factors may modify this relationship. Retrospective cross-sectional study. A subset of the National Long Term Care Survey (NTLCS), a Medicare-based U.S. population longitudinal study focused on trends of overall health and functional status in older adults. Six hundred and twenty-four individuals from the 1999 wave of the NTLCS cohort. Relative LTL determined according to quantitative polymerase chain reaction. LTL has previously been shown to correlate with common age-related disorders and mortality, as well as with socioeconomic status. A sex difference in LTL was observed but not age-dependent shortening or association with socioeconomic status. LTL was associated with disability and functional status assessed according to ADLs. The association between ADLs and LTL was stronger in subjects without diabetes mellitus, whereas associations were not seen when only subjects with diabetes mellitus were analyzed. Associations between LTL and cardiovascular disease (CVD) and cancer were also present in the group without diabetes mellitus but not in the group with diabetes mellitus. These findings support the concept that LTL is a biomarker of overall well-being that is predictive of disability of older individuals in the U.S. population. Diabetes mellitus plays an important role as a modifier of the association between LTL and disability, CVD, and cancer. These associations have clinical implications because of the potential predictive value of LTL and deserve further investigation.

Race/ethnicity and telomere length in the Multi‐Ethnic Study of Atherosclerosis

Telomere length has emerged as a marker of exposure to oxidative stress and aging. Race/ethnic differences in telomere length have been infrequently investigated. Leukocyte telomere length (LTL) was assessed 981 white, black and Hispanic men and women aged 45-84 years participating in the Multi-Ethnic Study of Atherosclerosis. Direct measurement and questionnaire were used to assess covariates. Linear regression was used to estimate associations of LTL with race/ethnicity and age after adjustment for sex, income, education, smoking, physical activity, diet and body mass index. On average blacks and Hispanics had shorter telomeres than whites [adjusted mean differences (standard error) in T/S ratio compared to whites: -0.041 (0.018) for blacks and -0.044 (0.018) for Hispanics]. Blacks and Hispanics showed greater differences in telomere length associated with age than whites (adjusted mean differences in T/S ratio per 1 year increase in age -0.0018, -0.0047 and -0.0055 in whites, blacks and Hispanics respectively). Differences in age associations were more pronounced and only statistically significant in women. Race/ethnic differences in LTL may reflect the cumulative burden of differential exposure to oxidative stress (and its predictors) over the lifecourse.

Leukocyte telomere shortening in elderly Type2DM patients with previous myocardial infarction

Objective We performed a cross-sectional study to examine the differences in leukocyte telomere length among three groups of subjects: patients with type 2 diabetes mellitus without history of previous myocardial infarction (Type2DM), patients with type 2 diabetes mellitus with evidence of previous myocardial infarction (Type2DM + MI), and healthy control subjects (CTR). The main objective of the present study is to investigate differences in telomere length between the studied groups of subjects, with the aim to clarify if telomere length could be a reliable marker associated with MI in Type2DM patients. Secondary end point is the identification of associations between leukocyte telomere length and selected variables related to glycemic control, pro-inflammatory status and lipidic profile. Research design and methods A total of 272 elderly subjects, 103 Type2DM (mean age 70 ± 4 years, 59% males), 65 Type2DM + MI (mean age 68 ± 7 years, 68% males), and 104 CTR (mean age 69 ± 7 years, 50% males) were studied. Telomere length, defined as T/S (Telomere-Single copy gene ratio), was determined in leukocytes by quantitative real-time polymerase chain reaction (real-time PCR)-based assay. Moreover, we assessed: (1) high sensitive C reactive protein (hsCRP), fibrinogen and plasminogen-activator inibitor-1 (PAI-1) as inflammatory markers; (2) fasting glucose, insulin, glycated haemoglobin (HbA1C) and waist-to-hip ratio as markers of glycemic control; (3) total-cholesterol, HDL-cholesterol and triglycerides as markers of lipidic profile, in all sample population. The use of statins and sulfonylurea, as well as the presence of some relevant diabetes complications (nephropathy and retinopathy) were also assessed. Conclusion Type2DM + MI elderly patients have leukocyte telomere lengths shorter than those of Type2DM (without MI) and healthy CTR. Moreover, glucose, HbA1C and waist-to-hip ratio, variables related to glycemic control, showed a significant inverse correlation with leukocyte telomeres length.

Leukocyte telomeres are longer in African Americans than in whites: the National Heart, Lung, and Blood Institute Family Heart Study and the Bogalusa Heart Study.

Leukocyte telomere length (LTL) is ostensibly a bio-indicator of human aging. Here we report that African Americans have longer LTL than whites. We studied cross-sectionally 2453 individuals from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study (age = 30–93 years) and the Bogalusa Heart Study (age = 19–37 years), comprising 1742 whites and 711 African Americans. We measured LTL by Southern blots of the terminal restriction fragments length. In 234 participants, telomere repeats were also measured by quantitative polymerase chain reaction (qPCR). Adjusted for age and body mass index (BMI), the respective leukocyte telomere lengths (mean ± SEM) were considerably longer in African Americans than in whites both in the Family Heart Study (7.004 ± 0.033 kb vs. 6.735 ± 0.024 kb, p < 0.0001) and the Bogalusa Heart Study (7.923 ± 0.063 kb vs. 7.296 ± 0.039 kb, p < 0.0001). We confirmed the racial effect on LTL by qPCR (3.038 ± 0.565 T/S units for African Americans vs. 2.714 ± 0.487 T/S units for whites, p < 0.001). Cross-sectionally, sex- and BMI-adjusted LTL became shorter with age (range 19–93 years) at a steeper slope in African Americans than in whites (0.029 kb year−1 vs. 0.020 kb year−1, respectively, p = 0.0001). We suggest that racial difference in LTL arises from a host of interacting biological factors, including replication rates of hematopoietic stem cells.

Higher serum vitamin D concentrations are associated with longer leukocyte telomere length in women

Background: Vitamin D is a potent inhibitor of the proinflammatory response and thereby diminishes turnover of leukocytes. Leukocyte telomere length (LTL) is a predictor of aging-related disease and decreases with each cell cycle and increased inflammation.Objective: The objective of the study was to examine whether vitamin D concentrations would attenuate the rate of telomere attrition in leukocytes, such that higher vitamin D concentrations would be associated with longer LTL.Design: Serum vitamin D concentrations were measured in 2160 women aged 18–79 y (mean age: 49.4) from a large population-based cohort of twins. LTL was measured by using the Southern blot method.Results: Age was negatively correlated with LTL (r = −0.40, P < 0.0001). Serum vitamin D concentrations were positively associated with LTL (r = 0.07, P = 0.0010), and this relation persisted after adjustment for age (r = 0.09, P < 0.0001) and other covariates (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity; P for trend across tertiles = 0.003). The difference in LTL between the highest and lowest tertiles of vitamin D was 107 base pairs (P = 0.0009), which is equivalent to 5.0 y of telomeric aging. This difference was further accentuated by increased concentrations of C-reactive protein, which is a measure of systemic inflammation.Conclusion: Our findings suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases.