Breaking new ground on human health and well-being with epigenetic clocks: A systematic review and meta-analysis of epigenetic age acceleration associations

Epigenetic clocks provide an accurate molecular readout of epigenetic age and epigenetic age acceleration (EAA) derived from DNA methylation data have shown promise as biomarkers of ageing. This systematic review synthesised research on associations between EAA measures and various physiological, cognitive, social, and environmental factors. A comprehensive search strategy identified 299 publications reporting 1050 unique EAA-factor associations based on 53 methylation clocks. Random-effects meta-analyses pooled results across studies for selected EAA-factor pairs. Significant pooled associations emerged, providing insights into relationships between specific factors and accelerated epigenetic ageing. We developed a novel four-level classification system to categorise this diverse range of factors and enable a structured synthesis. To aid further research planning in this rapidly evolving field, TEAPEE (Tracker of EAA Associations with Phenotype & Environmental Exposure) - an interactive, searchable web table detailing all EAA-factor associations - was developed, cataloguing the epigenetic clocks, associated factors, classification categories, and direct links to the original studies. This resource will empower future investigations into the multifaceted determinants of epigenetic ageing, contributing to a deeper understanding of the epigenome’s sensitivity to various life experiences and exposures.