Diet-induced leukocyte telomere shortening in a baboon model for early stage atherosclerosis.

Abstract

Reported associations between leukocyte telomere length (LTL) attrition, diet and cardiovascular disease (CVD) are inconsistent. This study explores effects of prolonged exposure to a high cholesterol high fat (HCHF) diet on LTL in a baboon model of atherosclerosis. We measured LTL by qPCR in pedigreed baboons fed a chow (n&#x2009;=&#x2009;105) or HCHF (n&#x2009;=&#x2009;106) diet for 2 years, tested for effects of diet on LTL, and association between CVD risk factors and atherosclerotic lesions with LTL. Though not different at baseline, after 2 years median LTL is shorter in HCHF fed baboons (P&#x2009;<&#x2009;0.0001). Diet predicts sex- and age-adjusted LTL and LTL attrition (P&#x2009;=&#x2009;0.0009 and 0.0156, respectively). Serum concentrations of CVD biomarkers are associated with LTL at the 2-year endpoint and LTL accounts approximately 6% of the variance in aortic lesions (P&#x2009;=&#x2009;0.04). Although heritable at baseline (h&#x2009;=&#x2009;0.27, P&#x2009;=&#x2009;0.027) and after 2 years (h&#x2009;=&#x2009;0.46, P&#x2009;=&#x2009;0.0038), baseline LTL does not predict lesion extent after 2 years. Atherogenic diet influences LTL, and LTL is a potential biomarker for early atherosclerosis. Prolonged exposure to an atherogenic diet decreases LTL and increases LTL attrition, and shortened LTL is associated with early-stage atherosclerosis in pedigreed baboons.