Social Determinants of Health, Biological Aging, and Their Impact on Frailty Risk: Mediation and Interaction Effects Analysis

OBJECTIVE: Social determinants of health (SDoH) are often associated with frailty outcomes, yet the potential role of biological aging (BA) in this relationship remains unclear. This study quantified BA-mediated (PhenoAge, Klemera-Doubal method biological age [KDM-Age]) pathways linking SDoH to frailty and assessed the predictive performance of the biological aging models for risk stratification. MATERIALS AND METHODS: Data from 10 763 participants in the National Health and Nutrition Examination Survey (NHANES) were analyzed. A composite SDoH score (0-8) was constructed across eight socioeconomic domains. Associations were evaluated via multivariable logistic regression, restricted cubic splines (RCS), and mediation analyses. XGBoost was trained to assess predictive performance and feature contributions. RESULTS: Each unit increase in SDoH score elevated frailty odds by 30%, with PhenoAge and KDM-Age mediating 1.19% and 1.25% of the association, respectively. High SDoH (> 6) synergized with accelerated BA to amplify frailty risk (RERI > 1). Age stratification showed null effects in adults > 75 years, supporting gerontological transition theories. CONCLUSION: SDoH adversity accelerates biological aging, synergistically amplifying frailty risk.