Social Connection and Epigenetic Aging: Insights from DNA Methylation Clocks.

Social connection is increasingly recognized as a determinant of healthy aging, yet the biological pathways through which it operates remain underexplored. Using data from the Health and Retirement Study (n = 2343), this study examined the associations of different dimensions of social connection (social isolation, loneliness, positive and negative relationship quality) with accelerated epigenetic aging measured by second-generation and third-generation clocks. Results from doubly robust estimation analyses revealed that baseline social isolation was associated with both the second- and third-generation clocks at 10-year follow-up (e.g., GrimAge2: ATE = 0.79, 95% confidence interval [CI] = [0.26, 1.33]), while loneliness was only associated with the third-generation clocks (e.g., DunedinPACE: ATE = 0.014, 95% CI = [0.001, 0.027]). Although relationship quality showed limited independent associations, co-occurring social connection deficits were associated with accelerated epigenetic aging, with the fastest epigenetic aging observed among individuals who were socially isolated, lonely, and with low positive and high negative relationship quality (e.g., DunedinPACE: 1.087, 95% CI = [1.066, 1.107] vs. 1.027, 95% CI = [1.019, 1.035]). Further analyses showed a longitudinal accumulation of social isolation was most strongly associated with accelerated epigenetic aging, whereas earlier loneliness exposures appeared to have the strongest associations. These findings highlight the importance of examining social connection both across multiple domains and over time.