Associations of Epigenetic Age Acceleration with Motor Impairment: Evidence from the PPMI Cohort

Accelerated epigenetic aging is robustly associated with the longitudinal progression of tremor impairment in PD, with associations being particularly consistent and multi-dimensional in men. These findings suggest that systemic biological aging, as captured by both first- and second-generation clocks, disproportionately exacerbates tremor circuitry distinct from the dopaminergic pathways that drive bradykinesia. Epigenetic clocks may serve as valuable biomarkers for monitoring progression and risk stratification, particularly for tremor-dominant phenotypes.