Social relationships and epigenetic markers of ageing in middle-aged and older adults: cross-sectional and prospective analyses

Abstract

Objectives: Social relationships play an important role in maintaining physical and psychological health. Epigenetic age is a potential mechanism underlying health-related aspects of social relationships. We aimed to assess the cross-sectional and prospective associations of social relationships and epigenetic age in middle-aged and older adults.

Methods: Blood DNA methylation data were collected from 6,208 participants in the Melbourne Collaborative Cohort Study at baseline (1990-1994, mean age = 59) and 1,110 at follow-up (2003-2007, mean age = 69). Four epigenetic ageing measures were considered: PCPhenoAge, PCGrimAge, bAge, and DunedinPACE. Social relationship variables were collected via self-reported questionnaires at baseline, including social activities, living arrangements, marital status, and numbers of close relatives and friends. A social isolation index was calculated. Linear regression was used to assess the associations of social relationships with baseline and follow-up epigenetic age.

Results: Cross-sectionally, living alone and overall social isolation were associated with older epigenetic age in men only (e.g., living alone, DunedinPACE, per SD β = 0.20, 95%CI: 0.10-0.29), with strong evidence of effect modification by sex (p = 0.002 to 4 × 10-5). Moderate amounts of social activities and a greater number of relatives and friends were also associated with a younger epigenetic age. Generally weaker associations were observed in prospective analyses.

Discussion: In middle-aged and older Australians, positive components of social relationships showed weak associations with lower epigenetic age. Social isolation and living alone were associated with older epigenetic age only in men. Our study suggests that the benefits of social relationships to health are partially captured by epigenetic markers of ageing.

Keywords: DNA methylation; biological ageing; living arrangement; social connectedness; social isolation.