Myelin plasticity is a key process for acquiring new motor skills and preventing neurodegeneration during ageing. Neural precursor cells (NPCs) and parenchymal oligodendrocyte precursor cells (OPCs) play a key role in myelin plasticity in the central nervous system (CNS), being specialized in reconstituting the myelin sheath upon damage. Reversible acetylation, regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs) activity, controls these stem cells’ differentiation in myelinating oligodendrocytes (mOLs) during their proliferation and remyelination processes. By modulating cytosolic protein activity and precisely orchestrating the spatial and timely regulated activity of the transcription factors participating in the NPC and OPC differentiation process, these enzymes play a vital role in preserving the adult brain’s cognitive capacity during ageing. This review highlights the role of reversible acetylation in the regulation of stem cell differentiation during remyelination, as disruptions in this process contribute to severe neurodegenerative impairments and accelerated ageing.