Exercise-induced modulation of neuroinflammation in aging.

Optimal performance of the central nervous system (CNS) depends on dynamic, multi-directional communication between different cell types both within and without the CNS to maintain the homeostatic environment. Aging, in turn, is associated with CNS disequilibrium resulting in suboptimal functioning of its cells and potential cognitive impairment. Emerging evidence indicates that inter-organ communication influences the functioning of CNS cell types, which are subject to age- and environment-dependent alterations. Endurance exercise has specifically been demonstrated to have a marked impact on neuroimmune communications particularly involving microglia, the resident macrophages of the CNS parenchyma, as well as microglia-astrocyte interactions in rodents. Via its action on CNS glial cells, regular aerobic exercise has been shown to provide an adaptive advantage against perturbations to homeostasis, such as immunological challenge or aging. In light of the accumulating evidence and evolutionary reasoning it may be argued that recurrent exercise-associated inter-organ signalling is necessary for the optimisation of glial function and hence CNS equilibrium. This, in turn, would imply that the absence of exercise-derived mediators and dysregulated inter-organ communication associated with a sedentary lifestyle may contribute to CNS dyshomeostasis which is accelerated during aging. As well as exploring the evidence of the impact of exercise on glial function, here we suggest potential next steps in identifying the mechanistic underpinnings of these effects and the potential importance of sex-differences. Abstract figure legend Aging and the associated inflammatory changes mediated by glia can lead to dysregulated homeostasis in the brain due to impairment of neuronal, and hence cognitive, function. Exercise can provide an adaptive advantage against such perturbations to homeostasis, enabling glia to perform their normal homeostatic and protective roles within the brain. This article is protected by copyright. All rights reserved.