An epigenetic aging-informed dietary pattern is associated with a spectrum of aging-related health outcomes.

Diet is associated with biological aging, yet few existing dietary indices have been developed specifically to target biological aging. We develop a data-driven, food-based Empirical Dietary Index for Slower Epigenetic Aging (EDISEA) to identify dietary features predictive of lower GrimAge2 acceleration. Higher EDISEA is associated with 4.17 years slower epigenetic aging in the derivation sample of 1,711 participants (P-value < 0.001) and 3.77 years slower aging in an independent sample of 2,311 participants. Higher EDISEA is consistently associated with lower all-cause mortality (pooled hazard ratio = 0.80, 95% CI 0.76, 0.85) in two US cohorts, and with lower risks of aging-related diseases, functional limitations, and multimorbidity across US and UK aging cohorts. Outcome-wide analyses in a large UK population-based cohort further show broad health associations, supported by molecular and neuroimaging signatures of more favourable vascular, inflammatory, metabolic, and brain structural profiles. EDISEA may provide an epigenetic aging-informed framework for studying dietary strategies relevant to healthy aging.