Epigenetic age acceleration is the degree to which epigenetic age is higher than chronological age. Epigenetic age is assessed via one of the epigenetic clocks, measuring the status of DNA methylation at numerous CpG sites on the genome. Some changes in DNA methylation patterns are characteristic of aging, a reaction to the accumulation of damage and dysfunction in aged tissues. People with lower epigenetic ages are, on balance, less burdened by the damage and dysfunction of aging than their peers. The caveat is that it is not yet understood what exactly causes any specific change in the patterns of DNA methylation, and thus while correlations with health and mortality risk show up quite reliably in study populations, one cannot yet draw much of a conclusion from the data for any given individual. A measurement of epigenetic age isn't yet actionable, and does little other than reinforce the general sentiment of "work to improve your health".
In 2010, the American Heart Association defined the construct of ideal cardiovascular health (CVH) as the simultaneous presence of 7 ideal health factors: healthy diet, absence of smoking, healthy body mass index (BMI), and optimal levels of physical activity, blood pressure, fasting glucose, and total cholesterol. Higher levels of CVH have been prospectively associated with greater longevity and healthy longevity, as well as markedly lower incidence of chronic diseases related to aging. Higher CVH is also associated with lower incidence of cardiovascular disease.
DNA methylation markers of aging have been aggregated into a composite epigenetic age score, which is associated with cardiovascular morbidity and mortality. However, it is unknown whether poor CVH is associated with acceleration of aging as measured by DNA methylation markers in epigenetic age. Thus we performed a cross-sectional analysis of racially/ethnically diverse post-menopausal women enrolled in the Women's Health Initiative cohort recruited between 1993 and 1998. Epigenetic age acceleration (EAA) was calculated using DNA methylation data on a subset of participants and the published Horvath and Hannum methods for intrinsic and extrinsic EAA. CVH was calculated using the AHA measures of CVH contributing to a 7-point score.
We examined the association between CVH score and EAA adjusting for self-reported race/ethnicity and education. Among the 2,170 participants analyzed, mean age was 64 (7 SD) years. Higher or more favorable CVH scores were associated with lower extrinsic EAA (6 months younger age per 1 point higher CVH score), and lower intrinsic EAA (3 months younger age per 1 point higher CVH score). This work provides initial evidence for epigenetic age acceleration to be considered as a potential early detection biomarker for CVH. Future studies are needed to evaluate if measures to promote optimal CVH through lifestyle and behavioral interventions could substantially alter an individual's epigenetic signature and the clinical utility of such a signature