Social determinants of health and epigenetic clocks: a systematic review and meta-analysis of 140 studies.

Social determinants of health-such as socioeconomic status (SES) and race and ethnicity-strongly shape health. Individuals with lower SES or marginalized identities experience earlier onset of disease and shorter lifespans. 'Epigenetic clocks' measure biological ageing and are increasingly used to study healthy ageing, yet it remains unclear which clocks are most sensitive to social inequality. Here we conducted an Open Science Framework-pre-registered systematic review and meta-analysis of 140 studies (N = 65,919; 1,065 effect sizes) testing associations of SES and race and ethnicity with three generations of clocks. PubMed, PsycINFO, Web of Science, medRxiv and bioRxiv were searched from February 2024 to September 2025. Eligible studies included empirical articles in English published since 2013 on non-clinical populations reporting at least one relevant association. Associations between SES and biological ageing varied across different generations of epigenetic clocks (F(2) = 178,10, P < 0.001), with the weakest effects for first-generation clocks (r = -0.03, 95% confidence intervaI (CI) [-0.04, -0.01], P < 0.001) and stronger effects for second- (r = -0.11, 95% CI [-0.12, -0.09], P < 0.001) and third-generation clocks (r = -0.13, 95% CI [-0.15, -0.11], P < 0.001]). Sex, tissue and array minimally modified results, and publication bias was negligible. Limitations include inconsistent reporting of technicalities and overrepresentation of data from high-income countries. The findings indicate that newer clocks are more responsive to social inequality.