Abstract P276: Metabolic Profiles of Biological Aging in American Indians: The Strong Heart Family Study

Background: Telomere length is an emerging biomarker for cellular senescence or biological aging. Short leukocyte telomere length (LTL) has been associated with a wide range of age-related metabolic disorders such as diabetes and cardiovascular disease. Telomere attrition induces profound metabolic dysfunction in animal models, but no study has examined the metabolic profiles of biological aging assessed by telomere length in human. Objective: To identify metabolic profiles of leukocyte telomere length in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003). Methods: This study included 432 SHFS participants free of cardiovascular disease and type 2 diabetes. LTL was measured by quantitative polymerase chain reaction (qPCR). Plasma metabolites were detected using an untargeted metabolomics approach by high-resolution liquid chromatography-mass spectrometry (LC/MS). The association of leukocyte telomere length with concentration of each metabolite was examined using generalized estimating equation (GEE), adjusting for age, sex, study center, body mass index, fasting glucose and fasting insulin. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: After adjusting for covariates and multiple testing, three metabolites including cytosine, selenophosphate and pentyl propanoate, were significantly associated with LTL. Of these, cytosine was positively associated with LTL (β=0.0476, 95% CI, 0.0474 to 0.0478, P=1.90х10-7), and selenophosphate (β =-0.1522, 95% CI, -0.1525 to -0.1519, P=2.48х10-8) and pentyl propanoate (β =-0.0644, 95% CI, -0.0683 to -0.0606, P=1.08х10-8) were negatively associated with LTL. Multivariate analysis demonstrated that participants with longer (top telomere tertile) and shorter (bottom telomere tertile) LTL can be clearly separated by partial least square discriminant analysis (PLS-DA) using these three metabolites. Multiple unknown compounds were also independently associated with LTL. Conclusions: This study, for the first time, identifies metabolites and metabolic profiles associated with interindividual variability in leukocyte telomere length, independent of potential confounders. Our findings provide novel insights into understanding of telomere biology and metabolic mechanisms underlying age-related disorders.

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Abstract P012: Short Leukocyte Telomere Length is Associated With Obesity in American Indians: The Strong Heart Family Study

Circulation ◽

10.1161/circ.129.suppl_1.p012 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Shufeng Chen ◽

Jue Lin ◽

Tet Matsuguchi ◽

Elizabeth Blackburn ◽

Elisa T Lee ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Waist Circumference ◽

Telomere Length ◽

American Indians ◽

Family Study ◽

Leukocyte Telomere Length ◽

Hip Circumference ◽

Waist To Hip Ratio ◽

Strong Heart Family Study

Background: Obesity is an independent risk factor for diabetes and cardiovascular disease. Telomere length shortens progressively with age, and shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders. However, the association between LTL and obesity has not been well established. Objective: To examine the association of LTL with obesity and related traits in American Indians participating in the Strong Heart Family Study (SHFS, 2001-2003), independent of known risk factors. Methods: A total of 3,162 participants (18-93 years old, 1,938 women) from 94 multigenerational families were included in this analysis. Obesity-related traits included body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio. LTL was measured by quantitative PCR. Association of LTL (continuous or in quintiles) with each adiposity index was examined using generalized linear mixed model, adjusting for age, sex, study center, education, lifestyle factors (current smoking, current drinking, physical activity, and total energy intake), hypertension (yes/no) and diabetes (yes/no). The association of LTL with prevalent obesity (BMI ≥30 kg/m2) was examined by multivariate logistic regression using the GLIMMIX procedure in SAS 9.3. Results: Prevalence of obesity was 59.6% (1,883 of 3,162). LTL was negatively correlated with age (r=-0.3, P<0.0001). Obese participants had significantly shorter LTL than non-obese participants (age-adjusted P=0.0004). Multivariate regression analyses demonstrated that, LTL was significantly and inversely associated with all obesity indices (β= -2.68 [95% confidence interval (CI), -3.96 [[Unable to Display Character: ‒]] -1.40] for BMI; -6.28 [95% CI, -9.29 [[Unable to Display Character: ‒]] -3.27] for waist circumference; -3.95 [95% CI, -6.61 [[Unable to Display Character: ‒]] -1.29] for hip circumference; and -0.02 [95% CI, -0.03 [[Unable to Display Character: ‒]] -0.01] for waist-to-hip ratio). Participants with shorter LTL had significantly larger BMI (P trend across quintiles =0.0006), waist circumference (P trend =0.0005), hip circumference (P trend =0.01), and waist-to-hip ratio (P trend =0.002) compared to those with longer LTL. Multivariate-adjusted odds ratio (95% CI) for prevalent obesity was 1.32 (1.05-1.67), 1.29 (0.99-1.67), 1.29 (1.01-1.65) and 1.18 (0.89-1.57), respectively, for the 1st through 4th quintiles of LTL in comparison with the 5th quintile (P for trend =0.02). Excluding participants with diabetes and cardiovascular disease did not change our results. Conclusion: Shorter LTL was significantly associated with obesity and related measures in American Indians, independent of known risk factors. Our results may shed light on the complex pathophysiology of obesity and its related disorders.

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