A data-driven dietary pattern anchored to slower epigenetic aging is associated with a spectrum of aging-related health outcomes

Abstract Diet is an essential factor influencing biological aging, yet few exsiting dietary indices were specifically developed to target biological aging. We developed a data-driven food-based Empirical Dietary Index for Slower Epigenetic Aging (EDISEA) in the US Health and Retirement Study (HRS, n=7,398), which predicted deceleration of GrimAge, an established DNA methylation-based epigenetic clock. Participants in the highest versus lowest EDISEA quintile had 4.65-year deceleration in GrimAge (P value <0.001). We externally validated EDISEA in an independent US cohort (n=23,830), where it showed consistent associations with several epigenetic clocks and lower all-cause mortality risk. In HRS and a UK aging cohort (n=4,895), EDISEA was associated with lower risks of several aging-related diseases and functional limitations. Outcome-wide analyses in the UK Biobank (n=187,035), together with integrative proteomic, metabolic, and neuroimaging assessments, revealed biological signatures of EDISEA implicating broad vascular, inflammatory, metabolic, and brain-structural pathways through which EDISEA was associated with biological aging. EDISEA provides a scalable, biologically anchored tool to inform the development of precision nutrition strategies aimed at slowing epigenetic aging and mitigating aging-related disease burden.