Dietary regulation of epigenetic aging: Beyond clocks to gene-specific mechanisms

Epigenetic aging, regulated by DNA methylation-based clocks, is a modifiable biological process influenced by environmental and lifestyle-related factors. Nutritional interventions have attracted attention as promising strategies to regulate biological aging. In this short review, we discuss the effects of specific nutrients and dietary patterns on epigenetic age acceleration and highlight the potential roles of diet-induced modulation of gene promoter methylation, a relatively underexplored yet critical mechanism underlying aging. We comprehensively reviewed the observational and interventional studies linking nutrient intake, dietary quality, and polyphenol-rich diets to slow epigenetic aging. Furthermore, we discuss the complementary impacts of nutrition-driven promoter methylation changes, revealing a potential dual pathway involved in the dietary regulation of aging at the global and gene levels. By bridging epigenetic clock(definition)-based aging and promoter methylation biology, this review provides novel insights and outlines future research directions for establishing precise nutritional approaches for healthy longevity. In addition, this review highlights the need to consider both global and locus-specific epigenetic markers when developing dietary strategies to modulate biological aging.