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Epigenetic clocks are widely applied as surrogates for biological age in different tissues and/or diseases, including several neurodegenerative diseases. Despite white matter (WM) changes often being observed in neurodegenerative diseases, no study has investigated epigenetic ageing in white matter.

We analysed the performances of two DNA methylation‐based clocks, DNAmClock_Multi and DNAmClock_Cortical, in post‐mortem WM tissue from multiple subcortical regions and the cerebellum, and in oligodendrocyte‐enriched nuclei. We also examined epigenetic ageing in control and multiple system atrophy (MSA) (WM and mixed WM and grey matter), as MSA is a neurodegenerative disease comprising pronounced WM changes and α‐synuclein aggregates in oligodendrocytes.

Estimated DNA methylation (DNAm) ages showed strong correlations with chronological ages, even in …