Microglia aging progresses through functional intermediate steps.. Microglia aging progresses through functional intermediate steps.

Aged microglia contribute to maladaptive inflammation, but little is known about their progression from homeostasis to dysfunction during aging. Here, we analyze the spatiotemporal kinetics of microglial aging in the hippocampus. Spatially, the dynamics of age-related inflammatory changes in microglia vastly differ across adjoining regions. Using single cell RNA-Sequencing and in vitro approaches, we find that microglia aging proceeds progressively through functional intermediate states that are necessary for inflammatory activation. Overall design: RNA-Seq of either Cx3cr1-CreERT::Tgfb1 fl/fl or Cx3cr1-CreERT::Tgfb1 fl/wt adult hippocampal microglia