13th Annual IGSS Conference • September 30-October 1, 2022

Integrating Genetics and the Social Sciences 2022

Familial loss in the early stages of the life course and biological aging of U.S. adults

Allison Aiello, Department of Epidemiology, Columbia Aging Center, Columbia University

The mechanisms underlying the link between early life loss, poor health, and mortality are unclear. Research suggests that loss may affect health through the decline of social and financial resources. These loss-related disadvantages may then initiate a host of risk factors for poor health. In addition, the psychological stress imposed by loss may directly alter immune, cardiometabolic, and inflammatory pathways in the body (Donnelly et al. 2022; Patterson et al. 2020; Yang et al. 2013; Yang et al. 2016). All of these potential mechanisms are known to impact biological aging. Yet, few studies have tested whether loss in either childhood or young adulthood is associated with DNA methylation markers of aging. To fill this gap, we utilized prospectively collected data from the National Longitudinal Study of Adolescent to Adult Health (Add Health) and new epigenetic data collected at Wave V to test the hypothesis that interpersonal loss leads to DNA methylation aging, as a potential early indicator of later life mortality risk. We examined both childhood and young adulthood familial loss as well as the number of losses on several epigenetic aging clocks measured when the Add Health cohort was average age 38 (range 33-43). We estimated linear regression models using the survey package in R (Lumley, 2011). Models were corrected for unequal selection probability and clustering of individuals within primary sampling units. Six models were estimated for each of the four epigenetic clocks - Horvath, GrimAge, PhenoAge, and Dunedin Pace of Aging (DunedinPACE). We found that loss, including parental loss and the number of losses, were associated with robust differences in epigenetic aging and the pace of aging. Of note, familial loss in young adulthood appeared to be more strongly predictive of epigenetic aging, independent of childhood losses. These results indicate that loss has long-lasting and profound associations with biological aging, even before adults reach middle age. Our findings suggest that epigenetic aging may represent a mechanism linking interpersonal loss in the early portion of the life course with morbidity and mortality.

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