Social determinants of health, accelerated biological aging, and long-term health outcomes.

Social determinants of health (SDHs) are the primary drivers of health inequalities, but whether biological aging plays a role in linking SDHs to health outcomes remains unclear. Here we utilize detailed information on social determinants across five domains, clinical parameters and electronic health records from the UK Biobank and US NHANES to examine the associations between combined SDHs, accelerated biological aging, and health outcomes. Compared with participants in the favourable SDH group, participants in the unfavourable SDH group had increased KDM-BA and phenotypic age acceleration. Moreover, unfavourable SDHs were associated with elevated risks of mortality and incident diseases. Accelerated biological aging significantly mediated the association between SDHs and all-cause and cause-specific mortality (UK Biobank: mediation proportion 13.46%-25.21%; US NHANES: 7.62%-22.16%). Also, accelerated biological aging served as a mediator between SDHs and incident diseases in the UK Biobank, with the mediation proportions ranging from 6.20% to 30.48%. The estimates were likely specific to the UK Biobank cohort considering its healthy volunteer bias and limited socioeconomic diversity. Overall, our study reveals that the biological aging discrepancy partially explains the associations of combined SDHs with mortality and chronic diseases. Assessing and delaying aging acceleration may be an effective way to narrow the health disparities caused by SDHs.