Brain HealthExercise Fights Brain Aging Through a Hidden Liver-Brain Signal
Scientists have uncovered a molecular chain reaction explaining how exercise protects the aging brain. In aged mice, 16 weeks of treadmill running boosted production of a liver hormone called FGF21. This hormone travels to the brain, where it activates a cellular cleanup process in microglia — the brain's immune cells — called mitophagy, which removes damaged mitochondria. Without functional mitophagy, toxic mitochondrial DNA accumulates inside cells, triggering a chronic inflammatory cascade known as cGAS-STING signaling. By restoring mitophagy through the AMPK-TFEB pathway, FGF21 suppresses this inflammation and reverses cognitive decline. The findings identify FGF21 as a druggable target for age-related cognitive decline, offering a potential pharmacological alternative for people unable to exercise.
