Direct pharmacological activation of AMPK extends lifespan in yeast, worms and flies
File(s)
Accepted version
Author(s)
Cocheme, Helena
Type
Journal Article
Abstract
AMP-activated protein kinase (AMPK) is a key evolutionarily conserved sensor of energy homeostasis, and plays a central role in metabolic health and disease. AMPK has also been implicated in ageing, however most in vivo drug studies rely on the use of indirect activators,
such as metformin, which have complex modes-of-action, therefore making conclusions on the specific role of AMPK more challenging. Here, we demonstrate that direct activation of AMPK with the compound 991 extends lifespan in Drosophila, C. elegans and S. pombe.
In mice, 991 treatment induces a pro-longevity proteomic profile, highlighting the potential for translation to mammals. Overall, our study provides important proof-of-principle for AMPK as a pharmacological target with longevity benefits.
such as metformin, which have complex modes-of-action, therefore making conclusions on the specific role of AMPK more challenging. Here, we demonstrate that direct activation of AMPK with the compound 991 extends lifespan in Drosophila, C. elegans and S. pombe.
In mice, 991 treatment induces a pro-longevity proteomic profile, highlighting the potential for translation to mammals. Overall, our study provides important proof-of-principle for AMPK as a pharmacological target with longevity benefits.
Date Acceptance
2026-09-04
Citation
Aging Cell
ISSN
1474-9718
Publisher
Wiley
Journal / Book Title
Aging Cell
Copyright Statement
Copyright This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
License URL
Publication Status
Accepted