Microglial cells undergo multiple morphological and immunophenotypic changes during normal aging. Abnormal morphology, which includes fewer and shorter ramifications, beading and spheroid swellings, has been observed particularly in the cerebral cortex, as well as in and around the white matter. In aged animals, microglia express some surface antigens which are not normally present in their young counterparts, in addition to presenting altered motility and phagocytosis. Aged microglia exhibit an aberrant production of pro- and anti-inflammatory mediators, accompanied by an exacerbated inflammatory response to pathological changes, a phenomenon known as microglial priming. Lysosomal dysfunction and mitochondrial DNA oxidative damage further accumulate in aged microglia, resulting in an increased production of reactive oxygen species. These changes could contribute to mediating the neuronal dysfunction observed during normal aging and facilitate the onset of age-associated cognitive decline, as well as neurodegenerative diseases. In this chapter, we describe microglial aging at the cellular and molecular levels, the implications for diseases, and potential strategies to slow down aging based on preserving lysosomal and mitochondrial function.
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