Age Associated Increase in Microglia Inflammation and Phagocytosis in the Adult Neural Stem Cell Niche

Adult SVZ neurogenesis declines with age, but the niche mechanisms remain incompletely defined. Here, we show that SVZ microglia acquire activation-associated morphology with aging. Reanalysis of published SVZ single-cell RNA-Seq data revealed that aged microglia upregulate inflammatory and lysosome/phagosome-related gene programs, including multiple phagocytosis-associated receptors and effectors. Functionally, young SVZ-derived microglia exhibit reduced basal phagocytic activity compared with non-SVZ microglia in vitro , whereas aged SVZ microglia show increased phagocytosis. In vivo SVZ wholemounts reveal increased progenitor-derived material within lysosomal compartments of microglia with age, without an accompanying increase in SVZ apoptosis. Inhibiting complement C3 activation or reducing inflammation with minocycline treatment partially restores SVZ proliferation in aged mice, but does not reduce progenitor-derived material within lysosomal compartments of aged microglia. These data support a model in which microglial inflammatory signaling contributes to age-related suppression of SVZ proliferation, while microglial engagement with neural progenitors is sustained by additional mechanisms.