Microglial senescence may be a key event in aging and Alzheimer’s disease. Free radical injury occurs naturally during aging affecting both microglia and neurons. It contributes to microglial senescence directly by causing oxidative injury in microglia, and indirectly by causing oxidative injury in neurons which elicits a low-level inflammatory response. The latter causes chronic stress to microglia contributing to exhaustion and senescence. If normal aging is exacerbated by acute injuries eliciting intense inflammation, this may accelerate naturally occurring microglial senescence.