This PhD research project aims to explore the impact of longevity interventions such as calorie restriction, exercise, the Mediterranean diet, and metformin on the aging epigenome. Changes to the epigenome, specifically DNA methylation, are a hallmark of aging and are associated with a range of age-related diseases including cardiovascular disease and cancer. (1) Several interventions have been shown to impact the epigenome and reverse these age-associated changes. (2) Exercise has been identified as a promising strategy for promoting healthspan and extending lifespan, with several studies suggesting that it can impact the epigenome and change gene expression patterns. The Mediterranean diet has demonstrated positive effects on various age-related diseases and is considered a promising approach for promoting healthy aging. Caloric restriction has been shown to extend lifespan and improve healthspan in various species. Metformin, a widely used anti-diabetic drug, has been identified as a promising geroprotective compound due to its ability to target key nutrient-sensing pathways. (2) The proposed methodology of this research project is to conduct a series of epigenome-wide association study (EWAS) meta-analyses of age in blood samples from previous clinical trials of these longevity interventions. The results of this research will add to the current understanding of the interplay between epigenetics and other factors to develop safe and effective clinical treatments to slow biological aging.