Researchers are increasingly finding that correlating epigenetic clock results with mortality in the context of specific interventions and lifestyle choices enhances the usefulness of these clocks. Despite the challenge of establishing accuracy and trustworthiness in assessing novel therapies, modern epigenetic clocks are reliable indicators of the benefits of common lifestyle choices. A study revealed that individuals with a high genetic risk for age-related diseases benefit more from a healthy lifestyle. The Life’s Essential 8 (LE8) metric for cardiovascular health demonstrated significant associations with a lower risk of cardiovascular disease and mortality, with mediation by epigenetic age biomarkers, particularly in individuals with a higher genetic predisposition for older epigenetic age. This highlights the importance of lifestyle choices in influencing epigenetic aging and overall health outcomes.
Life’s Essential 8 (LE8) is an enhanced metric for cardiovascular health. The interrelations among LE8, biomarkers of aging, and disease risks are unclear. LE8 score was calculated for 5,682 Framingham Heart Study participants. We implemented 4 DNA methylation-based epigenetic age biomarkers, with older epigenetic age hypothesized to represent faster biological aging, and examined whether these biomarkers mediated the associations between the LE8 score and cardiovascular disease (CVD), CVD-specific mortality, and all-cause mortality.
We found that a 1 standard deviation increase in the LE8 score was associated with a 35% lower risk of incident CVD, a 36% lower risk of CVD-specific mortality, and a 29% lower risk of all-cause mortality. These associations were partly mediated by epigenetic age biomarkers, particularly the GrimAge and the DunedinPACE scores. The potential mediation effects by epigenetic age biomarkers tended to be more profound in participants with higher genetic risk for older epigenetic age, compared with those with lower genetic risk. For example, in participants with higher GrimAge polygenic scores (greater than median), the mean proportion of mediation was 39%, 39%, and 78% for the association of the LE8 score with incident CVD, CVD-specific mortality, and all-cause mortality, respectively. No significant mediation was observed in participants with lower GrimAge polygenic score.
DNA methylation-based epigenetic age scores mediate the associations between the LE8 score and incident CVD, CVD-specific mortality, and all-cause mortality, particularly in individuals with higher genetic predisposition for older epigenetic age.
Link: https://doi.org/10.1161/JAHA.123.032743
