Inhibition of the neuromuscular acetylcholine receptor with atracurium activates FOXO/DAF-16-induced longevity.

ABSTRACT: Transcriptome-based drug screening is emerging as a powerful tool to identify geroprotective compounds to intervene in age-related disease. We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of FOXO3 (daf-16 in worms) overexpression, we could identify and repurpose compounds with similar downstream effects to increase longevity. Our in silico screen, utilizing the LINCS transcriptome database of genetic and compound interventions, identified several FDA-approved compounds that activate FOXO downstream targets in mammalian cells. These included the neuromuscular blocker atracurium, which also robustly extends both lifespan and healthspan in Caenorhabditis elegans. This longevity is dependent on both daf-16 signaling and inhibition

SUBMITTER: McIntyre RL 

PROVIDER: S-EPMC8373276 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature