Myelin undergoes structural changes with age. In mice, OLs born later in life elaborate increased numbers of myelin internodes, yet these are shorter than those generated in early postnatal life3. We have shown that myelination capacity of human OL lineage cells decreases postnatally through to adulthood87. With adulthood and ageing, there is a reduced amount of new myelin formed in the context of a learning task or following demyelination88,89, in association with impaired oligodendrogenesis. In addition, myelin structure becomes dysregulated particularly in the white matter, with myelin thickening, outfoldings, unravelling, enlargement of inner tongues90–92. Degeneration of myelin sheaths occurs with aging5, with particular vulnerability of newly discovered ‘bridging’ myelin sheaths, by which OLs generate sheaths via an extension of the outer tongue of an existing sheath93. Age is associated with poor efficiency of remyelination in animal models, and is a predominant risk factor for MS progression94.
