Direct AMPK activation extends lifespan across yeast, worms, and flies
Treatment with the direct activator 991 also induced a pro-longevity proteomic profile in mice.
In yeast, roundworms, and fruit flies, direct pharmacological activation of AMPK extends lifespan. Researchers studied the conserved energy sensor AMP-activated protein kinase, which plays a central role in metabolic health and aging. Previous in vivo drug investigations relied primarily on indirect activators such as metformin, which have complex mechanisms of action that obscure the precise role of AMPK. To test direct target engagement, investigators administered the direct AMPK activator compound 991 to Schizosaccharomyces pombe, Caenorhabditis elegans, and Drosophila melanogaster. The drug successfully prolonged lifespan in all three species. The authors also tested compound 991 in mice, where it induced a pro-longevity proteomic profile.
Why it matters
The study provides proof-of-principle that directly targeting AMPK with pharmacological activators can confer longevity benefits across evolutionary diverse organisms.
Caveats
Lifespan extension was documented only in non-mammalian organisms, as the mouse experiments assessed proteomic profiles rather than overall survival.
- Compound 991
- Deregulated nutrient-sensing
- AMPK signalling
- Pro-longevity proteomic profile
- Caenorhabditis elegans
- Drosophila melanogaster
- Mus musculus
- Schizosaccharomyces pombe
The paper
Direct Pharmacological Activation of AMPK Extends Lifespan in Yeast, Worms and Flies
Dos Santos E, Blickling M, Leiper FC et al.
Aging Cell · 30 Sep 2026