ArticleAging cell2021
Inhibition of the neuromuscular acetylcholine receptor with atracurium activates FOXO/DAF-16-induced longevity.
Article in Aging cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Longer lipids mark aging and constrain lifespan.Nature aging · 2026Article
- Aging clocks delineate neuron types vulnerable or resilient to neurodegeneration and identify neuroprotective interventions.Nature aging · 2026Article
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- T-CLASS: An Online Tool for the Identification and Classification of Aging and Senescence Using Transcriptome Data.Aging cell · 2025Article
- Immuno-metabolic stress responses control longevity from mitochondrial translation inhibition in C. elegans.Nature communications · 2025Article
- Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans.GeroScience · 2025Article
- The neuropeptide FLP-11 induces and self-inhibits sleep through the receptor DMSR-1 in Caenorhabiditis elegans.Current biology : CB · 2025Article
- Low-dose naltrexone extends healthspan and lifespan iniScience · 2024Article
- Article
- Dual-Acting Nitric Oxide Donor and Phosphodiesterase Inhibitor TOP-N53 Increases Lifespan and Health Span ofmicroPublication biology · 2024Article
- Peripheral modulation of antidepressant targets MAO-B and GABAAR by harmol induces mitohormesis and delays aging in preclinical models.Nature communications · 2023Article
- Biological Age Prediction From Wearable Device Movement Data Identifies Nutritional and Pharmacological Interventions for Healthy Aging.Frontiers in aging · 2021Article
Corrections and comments
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Authors and funding
14 authors.
Funding
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 of the neuromuscular acetylcholine receptor subunit unc-38. We found unc-38 RNAi to improve healthspan, lifespan, and stimulate DAF-16 nuclear localization, similar to atracurium treatment. Finally, using RNA-seq transcriptomics, we identify atracurium activation of DAF-16 downstream effectors. Together, these data demonstrate the capacity to mimic genetic lifespan interventions with drugs, and in doing so, reveal that the neuromuscular acetylcholine receptor regulates the highly conserved FOXO/DAF-16 longevity pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.