Social determinants of health and epigenetic clocks: Meta-analysis of 140 studies

Social determinants of health are social factors that affect health and survival. Two of the most powerful social determinants are socioeconomic status (SES) and race/ethnicity; people with lower SES or marginalized race/ethnicity tend to experience earlier onset of aging-related diseases and have shorter lifespans. DNA methylation (DNAm) measures of biological aging, often referred to as "epigenetic clocks", are increasingly used to study the social determination of health. However, there are several generations of epigenetic clocks and it remains unclear which are most sensitive to social factors affecting health. Moreover, there is uncertainty about how technical factors, such as the tissue from which DNA is derived or the technology used to measure DNA methylation may affect associations of social determinants with epigenetic clocks. We conducted a pre-registered multi-level meta-analysis of 140 studies, including N = 65,919 participants, encompassing 1,065 effect sizes for associations of SES and racial/ethnic identity with three generations of epigenetic clocks. We found that associations were weakest for the first generation of epigenetic clocks developed to predict age differences between people. Associations were stronger for the second generation of epigenetic clocks developed to predict mortality and health risks. The strongest associations were observed for a third generation of epigenetic clocks, sometimes referred to as "epigenetic speedometers", developed to predict the pace of aging. In studies of children, only the speedometers showed significant associations with SES. Effects of sex and technical factors were minimal and there was no evidence of publication bias.