Epigenetic aging and rejuvenation of the brain: drivers, consequences, and interventions

Evolution has tuned epigenetic resilience to preserve chromatin organization, transcriptional networks, and cellular identity under relentless stress. Over time, however, all eukaryotic life faces an inevitable rise in entropy that erodes the chromatin landscape at the genomic scale. This entropic decay of epigenetic information, epigenetic aging, is increasingly viewed as a key causal process underlying biological aging and systemic dysfunction. The brain is particularly vulnerable to epigenetic aging, with post-mitotic neurons accumulating lifelong chromatin erosion, and the glial epigenome drifting toward pro-inflammatory states. This review synthesizes evidence on the drivers and consequences of epigenetic aging in the brain and outlines frameworks for restoring youthful chromatin landscapes and cognitive capacity.