Epigenetic aging and rejuvenation of the brain: drivers, consequences, and interventions
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Evolution has tuned epigenetic resilience to preservechromatin organization, transcriptional networks, and cellularidentity under relentless stress. Over time, however, alleukaryotic life faces an inevitable rise in entropy that erodesthe chromatin landscape at the genomic scale. This entropicdecay of epigenetic information, epigenetic aging, is increasinglyviewed as a key causal process underlying biologicalaging and systemic dysfunction. The brain is particularly vulnerableto epigenetic aging, with post-mitotic neurons accumulatinglifelong chromatin erosion, and the glial epigenomedrifting toward pro-inflammatory states. This review synthesizesevidence on the drivers and consequences of epigeneticaging in the brain and outlines frameworks for restoring youthfulchromatin landscapes and cognitive capacity.
Abstract
Evolution has tuned epigenetic resilience to preservechromatin organization, transcriptional networks, and cellularidentity under relentless stress. Over time, however, alleukaryotic life faces an inevitable rise in entropy that erodesthe chromatin landscape at the genomic scale. This entropicdecay of epigenetic information, epigenetic aging, is increasinglyviewed as a key causal process underlying biologicalaging and systemic dysfunction. The brain is particularly vulnerableto epigenetic aging, with post-mitotic neurons accumulatinglifelong chromatin erosion, and the glial epigenomedrifting toward pro-inflammatory states. This review synthesizesevidence on the drivers and consequences of epigeneticaging in the brain and outlines frameworks for restoring youthfulchromatin landscapes and cognitive capacity.