Social isolation, loneliness, and biological aging acceleration.

OBJECTIVE: Social isolation and loneliness have been associated with several age-related health conditions. However, their effects on biological age acceleration (BAA) remain understudied. METHODS: The study analyzed data from 309,746 UK Biobank participants (Mage = 56.38 years, SD = 8.08, 54% female) over a median follow-up of 14.4 years. Self-reported questionnaires were used to gauge social isolation and loneliness. Multiple linear regression models and two-sample Mendelian randomization analysis were applied to estimate the associations between social isolation, loneliness, and BAA. Polygenic risk scores were calculated based on the single nucleotide polymorphisms related to BAA. Log-rank tests were conducted to assess the association between social isolation, loneliness, and mortality, with mediation analysis further employed to examine whether BAA mediated these associations. RESULTS: Social isolation (b = 0.17; 95% confidence interval [CI; 0.14, 0.19]) and loneliness (b = 0.15; 95% CI [0.12, 0.18]) were linked to BAA, with a cumulative effect observed. Although no interaction effects were identified between social isolation, loneliness, and genetic susceptibility to BAA, a superimposed effect was evident. Two-sample Mendelian randomization analyses determined that loneliness (b = 3.832; 95% CI [0.247, 7.417]) was linked to BAA, whereas regular club or gym attendance (b = -4.145; 95% CI [-7.622, -0.667]) and religious involvement (b = -3.244; 95% CI [-5.577, -0.913]) mitigated aging risk. Furthermore, each unit increment in social isolation and loneliness scores was associated with a 13.9% and 8.9% increase in all-cause mortality risk, respectively, and BAA partially mediated these associations. CONCLUSIONS: This study revealed significant associations between social isolation, loneliness, and BAA. (PsycInfo Database Record (c) 2026 APA, all rights reserved).