Social Connectedness and Cognitive Function in Later Life: GrimAge as an Epigenetic Mediating Pathway.

ObjectivesTo test whether epigenetic aging mediates associations between social connectedness and later cognitive function among U.S. older adults.MethodsUsing Health and Retirement Study data ( = 1,574; mean age = 68.5), we modeled 2014 social connectedness as a latent factor (participation, isolation, loneliness), assessed four DNA methylation clocks in 2016 (DNAmGrimAge, DunedinPoAm, DNAmPhenoAge, Zhang), and cognition in 2018. Survey-weighted regression-with-residuals mediation models adjusted for socio-demographics, smoking, obesity, self-rated health, heart disease, baseline cognition, and complex design.ResultsLower social connectedness predicted poorer 2018 cognition (ATE ≈ -0.047 to -0.048 across models, p < .05). Only DNAmGrimAge showed evidence consistent with mediation (NIE = -0.008, SE = 0.004, p = .041; ≈16% mediated), whereas indirect effects via DunedinPoAm, PhenoAge, and Zhang were not supported (all p > .05).DiscussionFindings provide limited, clock-specific support for epigenetic mediation, with preliminary evidence implicating DNAmGrimAge.