Ageing and CNS remyelination.

Remyelination of demyelinated axons in the CNS is a regenerative process that, like many others, becomes less efficient with age. This article reviews a series of studies in which toxin models of demyelination have been used to characterize this phenomenon. The delayed rate of remyelination in older animals is associated with a decrease in the rate of oligodendrocyte progenitor recruitment and in the rate at which the recruited cells differentiate into remyelinating oligodendrocytes. The differences in the behaviour of oligodendrocyte lineage cells during remyelination in young and old animals are related to the age-related changes that occur in the expression of growth factors that affect the proliferation, migration and differentiation of oligodendrocyte progenitors, and in the inflammatory process associated with toxin-induced demyelination. Based on these differences, a conceptual framework is proposed to explain the age-associated effects on remyelination, which we have called the dysregulation hypothesis, and the feasibility of reversing these effects is discussed.