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.