The Socioeconomic Gradient in Epigenetic Aging Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study

Epigenetic clocks have been widely used to predict disease risk in multiple tissues or cells. Their success as a measure of biological aging has prompted research on the connection between epigenetic pathways of aging and the socioeconomic gradient in health and mortality. However, studies examining social correlates of epigenetic aging have yielded inconsistent results. We conducted a comprehensive, comparative analysis of associations between various dimensions of socioeconomic status (SES) (education, income, wealth, occupation, neighborhood environment, and childhood SES) and eight epigenetic clocks in two large U.S. aging studies: The Multi-Ethnic Study of Atherosclerosis (MESA) (n=1,211) and the Health and Retirement Study (HRS) (n=4,018). In both studies, we found robust associations between SES measures in adulthood and the GrimAge and DunedinPoAm clocks (Bonferroni corrected p-value<0.01). In the HRS, significant associations with the Levine and Yang clocks are also evident. These associations are only partially mediated by smoking, alcohol consumption, and obesity, which suggests that differences in health behaviors alone cannot explain the SES gradient in epigenetic aging. Further analyses revealed concurrent associations between polygenic risk for accelerated intrinsic epigenetic aging, SES, and the Levine clock, indicating that genetic predisposition and social disadvantage may contribute independently to faster epigenetic aging.