Associations Between Loneliness, Epigenetic Aging, and Multimorbidity Through Older Adulthood

Objectives. Loneliness is a pressing public health concern, but the mechanisms by which it leads to declining physical health are uncertain. Prior work has begun to explore epigenetic pathways, with some evidence suggesting a link between loneliness and DNA methylation, though it is unclear whether epigenetic variation can help explain loneliness–health associations. Methods. Associations between loneliness and epigenetic age acceleration (EAA) were estimated, as well as the degree to which EAA mediated and moderated the association between loneliness and the development of chronic physical health conditions (multimorbidity) in older adulthood. The sample consisted of Health and Retirement Study participants who provided blood draws and consented to methylation profiling (n = 4,018). Results. Baseline loneliness was associated with greater EAA in the GrimAge measure net of demographic and behavioral covariates (β = 0.07, p = .003). Loneliness and GrimAge each predicted increasing condition counts, but there was no evidence of an interactive effect. The association between loneliness and increasing condition counts was, however, significantly mediated by GrimAge (indirect path β = 0.020, p = .003). Discussion. These results suggest that the impact of loneliness on multimorbidity may, in part, operate through DNA methylation. The specific intermediary, physiological mechanisms that are involved will require further research, but EAA measures like GrimAge are promising in helping to understand the health impacts of loneliness.