Greenspace Exposure and DNA Methylation Age Acceleration: A Systematic Review and Molecular Pathway Analysis

Residential greenness has been consistently associated with multiple health benefits; however, the underlying molecular mechanisms remain insufficiently understood. DNA methylation-based epigenetic clocks have emerged as robust biomarkers of biological aging and provide a valuable framework for investigating environmental influences on aging processes. This systematic review synthesizes current human evidence linking greenspace exposure to epigenetic age acceleration and DNA methylation changes. Following PRISMA 2020 guidelines, we searched Scopus and Web of Science databases (inception to May 2026). Studies were eligible if they assessed quantitative indicators of greenspace exposure and DNA methylation-based aging biomarkers in human populations. Out of 97 identified records, 14 studies met the inclusion criteria. Higher levels of greenspace exposure were consistently associated with a deceleration of GrimAge acceleration, with effect sizes ranging from 1.0 to 1.6 years per interquartile range increase in greenness. At the molecular level, greenspace-associated differentially methylated regions (DMRs) were consistently enriched in genes involved in neurodevelopment (HTR2A, BDNF, SLC6A3, SDK1), immune regulation (HLA-DRB5, IL6), stress response (NR3C1), and extracellular matrix remodeling (ADAMTS2). Overall, greenspace exposure is associated with slower epigenetic aging and differential DNA methylation across key biological pathways. These findings support the concept of greenspace as an epigenomic resilience factor and highlight its potential role in modulating molecular mechanisms of aging.