Brain aging
Summary
Brain aging refers to the normal age-related changes in brain structure, function, and cellular biology, distinct from but predisposing to neurodegenerative disease. Microglial aging (microglial senescence and dysfunction) is increasingly recognized as a driver of age-related cognitive decline and disease vulnerability.
Microglial Relevance
Microglia undergo significant functional changes during normal aging, including reduced surveillance velocity, altered morphology, increased proinflammatory signaling, and accumulation of lipid droplets. Aged microglia show a transcriptional signature distinct from both homeostatic and disease-associated states, sometimes called 'aging-associated microglia' (AAM). C1QA is markedly upregulated in aged brain and mediates age-related synaptic pruning. P2RY12 and CX3CR1 expression decline with age. TREM2 function is required for clearance of age-related debris. Understanding which aging-associated microglial changes predispose to neurodegeneration versus protect against it is a central unresolved question.
Sources
- The aging brain microenvironment and microglial senescence (2021)
Last reviewed: June 1, 2026