Mechanism

AMPK

Established evidence

AMPK (AMP-activated protein kinase) is the cell's low-fuel sensor. When energy runs low it switches cells from growth to repair and maintenance — one of the core pathways behind the metabolic benefits of fasting and exercise.

Also known as: AMPK, AMP-activated protein kinase

AMPK is an enzyme that acts as the cell's main energy gauge. It switches on when the ratio of AMP and ADP to ATP rises — that is, when the cell is running low on usable energy, as happens during fasting, caloric restriction, and exercise.

When AMPK is active it shifts the cell away from energy-consuming growth programs and toward energy-producing maintenance: it promotes fat and glucose oxidation, stimulates mitochondrial biogenesis, and helps trigger autophagy, the cell's recycling system. It also restrains mTOR, the growth-driving pathway — the two behave as opposing arms of a single metabolic switch.

This is why AMPK sits at the centre of the longevity interest in fasting and caloric restriction: interventions that raise AMPK activity tend to engage the same repair and stress-resistance programs linked to healthier aging in laboratory models. The diabetes drug metformin is thought to act in part through AMPK. Human longevity outcomes remain unproven, however — most of the lifespan evidence is mechanistic or from animal studies.

Sources & references

  1. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nature Reviews Molecular Cell Biology. doi:10.1038/nrm.2017.95
  2. González A, Hall MN, Lin SC, Hardie DG. AMPK and TOR: The Yin and Yang of Cellular Nutrient Sensing and Growth Control. Cell Metabolism. doi:10.1016/j.cmet.2020.01.015

In our articles

Related terms

Educational information, not medical advice. Evidence ratings follow our methodology.