Longevity & AgingAMPK Pathway Emerges as Master Switch for Mitochondrial Rejuvenation
AMPK (AMP-activated protein kinase) is an ancient, evolutionarily conserved energy sensor found in all eukaryotes. When cellular ATP falls, AMPK activates a coordinated program that simultaneously promotes mitochondrial fission to isolate damaged organelles, triggers mitophagy to clear them via lysosomes, and stimulates biogenesis to synthesize fresh mitochondria. Upstream kinases LKB1 and CAMKK2 phosphorylate AMPK at Thr172 to fully activate it. Pharmacological activators—including the diabetes drug metformin and direct ADaM-site agonists like MK-8722—mimic exercise-induced AMPK activation. Dysregulation of these AMPK-governed processes is implicated in neurodegeneration, cancer, and aging, making AMPK a compelling therapeutic target for longevity-related metabolic diseases.
