How it works
AMPK (AMP-activated protein kinase) is a cellular energy sensor that switches on when energy is low — mimicking the effects of caloric restriction and exercise. It activates autophagy, fatty-acid oxidation, and mitochondrial biogenesis while suppressing mTOR and fat synthesis. Most longevity interventions with strong evidence converge on AMPK activation.
Evidence overview
Compounds that activate AMPK through direct or indirect mechanisms: berberine and gynostemma (plant-derived direct activators), metformin (clinically the most-studied), green tea EGCG and resveratrol (indirect/allosteric), and alpha-ketoglutarate (TCA-cycle route via mTOR suppression and TET activation).
An alkaloid from Chinese herbs (Coptis / Huang Lian) with human RCTs on metabolic health and an AMPK/sirtuin longevity rationale.
The diabetes drug at the center of the longevity debate — and the TAME trial designed to test aging itself.
The most-studied tea catechin, linked to lifespan and healthspan in models via AMPK, sirtuin and FOXO pathways.
A TCA-cycle metabolite that suppresses mTOR, co-factors DNA demethylation, and showed biological-age reduction in a 2023 human RCT.
“Southern ginseng,” a Chinese herb whose gypenosides activate AMPK — the metabolic longevity pathway.
The grape-and-knotweed polyphenol that launched the sirtuin era of longevity research.
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