Microglia in the Aging Brain

The aging brain is characterized by a demonstrable decrease in weight and volume, particularly after the age of 50. This atrophy, which affects both grey and white matter, is presumed to result from a loss of neurons and myelinated axons. Glial cells, on the other hand, appear to increase in the aging brain, which exhibits greater immunoreactivity with both astrocytic and microglial markers. This review is focused on the morphologic and phenotypic changes that occur in microglial cells with normal aging. Although there is a consistent aging-related upregulation of microglial activation markers in experimental animals and humans that could be interpreted as aging-related neuroinflammation, it is generally difficult to show a direct correlation between ostensible microglial activation and neurodegeneration. This raises questions about whether aging-related microglial activation indeed represents reactive gliosis in the conventional sense. As an alternative, we discuss the possibility that structural and phenotypic changes that occur in microglia are a direct reflection of the aging process on microglia. Thus, microglia cells themselves may be subject to cellular senescence in the sense that they no longer function efficiently. The concept of microglial senescence offers a novel perspective on aging-related neurodegeneration, namely that neurodegeneration could also occur secondary to microglial degeneration.