Oligodendroglial changes in ageing human white matter

Myelin is essential for superfast conduction of axons and underpins the massive computing power of the human brain. Myelinated axons form bundles of white matter to form the connectome which is one of the most prominent features of the human cerebral cortex. Myelin is produced by oligodendrocytes, which are the most numerous cells in white matter, together with oligodendrocyte precursor cells (OPC) that are responsible for life-long myelination. Myelin is essential for cognitive function and myelin plasticity is required for learning. It is noteworthy, therefore, that white matter shrinkage and myelin loss are hallmarks of natural ageing and are more severe in neuropathology, including multiple sclerosis and Alzheimer’s disease, as well as neuropsychiatric disorders such as schizophrenia. The precise age-related changes in oligodendroglial gene pathways at the transcriptome level identify the decline in oligodendrocyte regeneration as a key factor in white matter shrinkage in ageing.