Longevity & AgingBrain Glial Cells Have Unique Circadian Clocks That Break Down in Alzheimer's and Aging
Researchers used cell-type-specific ribosome-tagging techniques (TRAP/RiboTag) to map 24-hour gene expression cycles in astrocytes and microglia from mouse cortex under three conditions: healthy young, amyloid plaque-bearing (Alzheimer's model), and aged. Each glial cell type had a distinct circadian translatome. Both amyloid pathology and aging caused dramatic, cell-type-specific 'circadian reprogramming'—gaining and losing rhythmic gene expression in pathways governing neuroinflammation, immune metabolism, and protein clearance. Nearly half of all known Alzheimer's disease risk genes showed circadian oscillations, many altered by disease. Microglial functions like oxidative stress response and amyloid phagocytosis also showed time-of-day variation, suggesting when microglia are sampled significantly affects experimental results.
