Epigenetic Age Acceleration
A Biological Doomsday Clock for Cardiovascular Disease?
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See Article by Roetker et al
Epigenetic age seems like a concept pulled from a futuristic science-fiction movie where a drop of blood is fed into a machine, in which an algorithm churns through an accumulation of chemical groups coating a strand of DNA and spits out an individual’s true age reflecting a lifetime of experiences and exposures. Remarkably, this fiction moved closer to reality with astute observations that DNA methylation patterns predictably change over time and are highly correlated with age.1 These observations and the proliferation of high-density methylation microarrays on large sample sizes led to the application of machine-learning approaches to sift through the high-dimensional methylomic data to identify a parsimonious set of informative markers to reconstruct an individual’s age; 2 popular sets were proposed by Horvath2 and Hannum et al3 in 2013, although various subsequent adaptations have been developed. These DNA methylation-predicted ages turn out to perform remarkably well; demonstrating very strong correlations with chronological age. Although the novelty of using an overly complicated and costly Rube Goldberg machine approach to determine something that only requires a simple question to obtain holds a peculiar appeal, real-world use cases are evident; such as in a forensics scenario where accurately predicting the age of an individual from an unidentified blood or tissue sample clearly has utility.4 The possibility of cardiovascular health applications arose when the divergence between DNA methylation-predicated age and chronological age, commonly referred to as epigenetic age acceleration, was found to be linked to clinical traits. A positive or accelerated epigenetic age occurs when an individual’s DNA methylation-predicted age is older than their chronological age.
Epigenetic Age Acceleration and Cardiovascular Disease
In this issue of Circulation: Genomics and Precision Medicine, Roetker et al5 report the association of epigenetic age acceleration with the risk of cardiovascular disease (CVD). …