Evolutionary conserved lifespan extension by direct pharmacological activation of AMPK

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 proof-of-principle for AMPK as a pharmacological target with longevity benefits.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Proteomics Facility  

LAB HEAD: Filipe Cabreiro

PROVIDER: PXD065733 | Pride | 2026-10-05

REPOSITORIES: Pride