The impact of astrocyte mitochondrial metabolism on neuroprotection during aging

Abstract

Accumulation of oxidative damage as the result of normal mitochondrial metabolism is widely considered to be a fundamental cause of aging. A central tenet of this theory is that mitochondria themselves become dysfunctional. In the central nervous system (CNS), the focus of research on aging has primarily revolved around changes in and effects of neuronal mitochondrial metabolism. However, there is increasing interest in the role that astrocyte mitochondria play in the aging process. Little is known about the cumulative effects of aging on astrocyte mitochondria or on energy-dependent processes within astrocytes. It is likely that diminished astrocyte function throughout the aging process is a prominent determinant of both neuronal survival as well as survival of the entire organism. In this chapter, we focus our discussion on the impact of astrocyte mitochondrial metabolism during the aging process. We present a brief review of astrocyte bioenergetics followed by a discussion of our recent work on decreased astrocyte neuroprotection during aging. We then discuss our ongoing work on a neuroprotective pathway that is mediated by increased mitochondrial metabolism in astrocytes. This pathway is activated by G-protein-coupled receptors that stimulate inositol 1,4,5 trisphosphate (IP3)-gated Ca2+ release. Astrocyte neuroprotection can be enhanced in both young and old astrocytes to the point that their neuroprotective functions are nearly comparable.