Telomeres and Atherosclerosis
The Intricate Pursuit of Mechanistic Insight Through Epidemiology
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See related article, pp 420–425
The discovery that critical telomere shortening initiates replicative senescence triggered a vast body of epidemiological studies exploring its implications for human aging. These studies demonstrated that telomeres—typically measured in the DNA isolated from blood cells—clearly shorten with age. On average, shorter telomeres were found in subjects with atherosclerosis and independently predicted atherosclerotic cardiovascular disease (ACVD)–associated mortality. Moreover, Mendelian randomization studies point to a causal role for shorter telomere length in ACVD, lending support to the hypothesis that the protective antitumor mechanism elicited by critical telomere attrition may act at the expense of unsuccessful cardiovascular aging.1 Yet, consensus is lacking on the mechanism underlying the presumed associations between shorter telomeres, atherosclerosis, and ACVD. This problem was addressed in the epidemiological research by Toupance et al,2 published in the current issue of Hypertension. In a longitudinal study, both leukocyte telomere length and carotid atherosclerosis were quantified in 154 subjects at baseline and after a 9.5-year follow-up, and their interrelation was evaluated. More specifically, 2 competitive hypotheses on the role of telomeres as primary risk factor for ACVD were scrutinized: (1) shorter (inherited) telomeres versus (2) higher telomere attrition rates (Figure). The study provides evidence supporting the first hypothesis. In this commentary, we focus on embedding these results in the current state of the art and highlight the potential of inferring insight from epidemiological surveys.