AMPK
The cellular energy sensor that activates longevity pathways when ATP runs low
Definition
AMPK (AMP-activated protein kinase) is an enzyme that senses the energy status of the cell. It is activated when the AMP/ATP ratio rises — that is, when cellular energy is low — and triggers a cascade that stimulates catabolism (fatty-acid oxidation, autophagy, mitochondrial biogenesis) and inhibits anabolism (cholesterol, lipid, and protein synthesis). It is one of the main antagonists of mTOR and a central target of longevity interventions.
Detailed explanation
AMPK is activated physiologically by aerobic exercise, prolonged fasting, caloric restriction, and extreme cold; and pharmacologically by metformin and berberine. Its activation favours inhibitory phosphorylation of mTORC1 and activation of PGC-1α, the master regulator of mitochondrial biogenesis.
Studies in animal models have shown that chronic moderate AMPK activation extends lifespan in C. elegans, Drosophila, and mice. In humans, metformin — an indirect AMPK activator — is associated with lower incidence of cancer, dementia, and all-cause mortality in observational studies such as Bannister (2014), the basis for the TAME trial (Targeting Aging with Metformin).
AMPK is also essential in insulin-independent muscle glucose uptake, making it a key target for prevention of type 2 diabetes and metabolic syndrome.
Scientific sources
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