Epigenetic age acceleration predicts subject-specific white matter degeneration in the human brain.

Epigenetic clocks provide powerful tools for estimating health and lifespan but their ability to predict brain degeneration and neuronal damage during the aging process is unknown. This study uses the epigenetic clock GrimAge to longitudinally investigate brain cellular microstructure in axonal white matter from a healthy aging cohort. We reconstructed subject-specific axonal networks damaged by white matter hyperintensities, a visible neurological manifestation of small vessel disease. A chronological age-adjusted version of GrimAge was significantly correlated with longitudinal markers of neuronal decline. This study is the first to establish a relationship between accelerated epigenetic GrimAge and brain cellular microstructure in humans.