Researchers used single-cell RNA sequencing to map how microglia—the brain's immune cells—change during aging in the mouse hippocampus. They discovered that microglia don't simply switch from healthy to dysfunctional states, but progress through intermediate cellular states including stress response and enhanced protein synthesis phases. These intermediate states can be modulated and directly influence whether microglia become inflammatory. When researchers blocked TGFβ1 signaling in aged microglia, it accelerated progression through these states and worsened cognitive decline, suggesting these intermediate phases represent potential therapeutic targets for age-related neuroinflammation.
