Abstract 3943: Reference Values and Basic Determinants of Telomere Length in a Large Middle-Aged Population
Telomeres are specialized structures at the termini of linear chromosomes that safeguard the genome. Telomere length (TL) has been put forward as a putative biomarker for biological aging. Recently, mean TL of leukocyte populations within peripheral blood samples has been demonstrated to be correlated with several key cardiovascular parameters and accelerated telomere attrition is found to be implicated with atherosclerosis and cardiovascular mortality. Current knowledge on telomere shortening is based on cross-sectional analysis and both reference values and a complete set of basic determinants are missing. In an attempt to link telomeric aging to specific aging phenotypes, we are evaluating its multiple risks-adjusted prognostic value in the broader context of cardiac pathophysiology in general and more particularly of atherogenesis. We successfully assessed mean TL of peripheral blood leukocytes in a large representative cohort of 2514 apparently healthy, community-dwelling, Caucasian female and male volunteers aged approximately 35–55 years at study initiation. The subjects were sampled from the twinned Belgian communities of Erpe-Mere and Nieuwerkerken. The study will be repeated on a 4-year base during 12 years, enabling the assessment of indivual telomere dynamics in vivo. Even within the narrow age range, we found an age-dependent telomere shortening and we show that this shortening is faster in men, explaining the difference in TL between both sexes. In both sexes TL was correlated with oxidative stress parameters such as log transformed hs-CRP and ox-LDL (borderline for men), while only in men a significant correlation with IL6 was established. All correlations were age-adjusted where appropriate. Furthermore we show a link between mean TL and parental survival. We are currently evaluating the value of TL as biomarker in the risk analysis of the different atherosclerotic phenotypes This new evidence supports the hypothesis of TL being an aging biomarker, especially in the cardiovascular context. The longitudinal continuation will provide a definitive validation. We will present the results of the first round of this longitudinal study about telomere distribution in this middle-aged population.