The effect of aging and senescence on the process of remyelination

Aging has been shown to detrimentally affect oligodendrocyte function in axon remyelination. Examining what changes cause these detrimental effects can improve our understanding of the critical processes controlling this regenerative process. Since declined remyelination is a hallmark of demyelinating diseases like Multiple Sclerosis (MS), investigation of the aging process would be of interest in pursuit of future therapies. In addition, since MS is a disease that can last for several decades aging is a likely contributing factor in disease progression. Therefore, devising a means of combating the aging trend also seems to represent a promising approach to MS therapy itself. By reviewing the present data, a picture emerges in which oligodendrocyte differentiation is the most likely limiting step in the declined remyelination efficiency of the aged individual. During the differentiation stage aging has been shown to cause adverse changes in the epigenetic make-up of oligodendrocyte lineage cells, accompanied by changes in the expression of transcriptional regulators of remyelination. In addition, harmful changes have been reported in the environment of these cells - including changes in growth factor expression, immune factor response, and the activity of remyelination inhibiting proteins. As this evidence points to aging as multifactorial process, it is likely that therapies targeting normalization of only one of these factors would not improve remyelination. Instead, the only profitable approach will be to simultaneously modify a multitude of these components. Besides the enhancement of endogenous remyelination, strategies to increase the degree of remyelination could also aim to circumvent the endogenous repair process by transplanting myelinogenic cells. As knowledge about the remyelination process is growing, both strategies might be exploited in future MS therapy. Since endogenous remyelination declines with age the strategy that proves to be most beneficial is likely to depend on the individual patient.