Gene
PRKAG2
Last updated 2026-07-02· Last reviewed 2026-07-02· 1 min read
Reviewed by the Ultimate Longevity Bible editorial team. Educational reference — not medical advice. See disclaimer.
AMPK biology
- Activated by high AMP:ATP ratio (energy stress).
- Downstream effects: fatty-acid oxidation, autophagy, glucose uptake — the metabolic "emergency response".
- Target of metformin, exercise, and caloric restriction — all activate AMPK indirectly.
PRKAG2 syndrome
- Gain-of-function mutations activate AMPK independent of energy status.
- Manifests as glycogen accumulation in cardiomyocytes, hypertrophic cardiomyopathy, pre-excitation (WPW syndrome), and heart block.
- Rare autosomal-dominant condition — illustrates that too much AMPK activation is not benign.
Longevity relevance
- AMPK as a longevity target: activate it enough to gain metabolic benefits without triggering pathology.
- Metformin, exercise, CR: all AMPK activators; their efficacy is bounded by exactly this trade-off.
- Human population variants in AMPK genes are being studied for association with metabolic health and longevity.
- Levels (CGM Service) — Clinic.
- Deregulated Nutrient-Sensing — Hallmark.
- Berberine — Intervention.
- PGC-1α (Mitochondrial Biogenesis) — Pathway.