Aging impacts nearly every tissue and function in an organism, and the associated deterioration is the primary risk factor for major human diseases, including cancer, cardiac disease and such neurodegenerative diseases as Alzheimer’s. The underlying cause of aging is likely a multifaceted yet interconnected tangle of processes, and accumulating evidence suggests that in the brain, microglia—the resident immune cell—play a major role. We discovered that these cells show profound changes with aging, and that soluble factors in the blood of young mice can rejuvenate these cells. We propose here to study how microglia age and determine the mechanism of rejuvenation. Our studies will help characterize the role of microglia in brain aging and may uncover new ways to rejuvenate these cells to slow brain aging and neurodegeneration.