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We hypothesized that, by mimicking the transcriptional signature of the highly conserved longevity intervention of\n                    <jats:italic>FOXO3<\/jats:italic>\n                    (\n                    <jats:italic>daf<\/jats:italic>\n                    \u2010\n                    <jats:italic>16<\/jats:italic>\n                    in worms) overexpression, we could identify and repurpose compounds with similar downstream effects to increase longevity. Our\n                    <jats:italic>in silico<\/jats:italic>\n                    screen, utilizing the LINCS transcriptome database of genetic and compound interventions, identified several FDA\u2010approved compounds that activate FOXO downstream targets in mammalian cells. These included the neuromuscular blocker atracurium, which also robustly extends both lifespan and healthspan in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    . This longevity is dependent on both\n                    <jats:italic>daf<\/jats:italic>\n                    \u2010\n                    <jats:italic>16<\/jats:italic>\n                    signaling and inhibition of the neuromuscular acetylcholine receptor subunit\n                    <jats:italic>unc<\/jats:italic>\n                    \u2010\n                    <jats:italic>38<\/jats:italic>\n                    . We found\n                    <jats:italic>unc<\/jats:italic>\n                    \u2010\n                    <jats:italic>38<\/jats:italic>\n                    RNAi to improve healthspan, lifespan, and stimulate DAF\u201016 nuclear localization, similar to atracurium treatment. Finally, using RNA\u2010seq transcriptomics, we identify atracurium activation of DAF\u201016 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\u201016 longevity pathway.\n                  <\/jats:p>","DOI":"10.1111\/acel.13381","type":"journal-article","created":{"date-parts":[[2021,7,6]],"date-time":"2021-07-06T04:44:24Z","timestamp":1625546664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Inhibition of the neuromuscular acetylcholine receptor with atracurium activates FOXO\/DAF\u201016\u2010induced longevity"],"prefix":"10.1111","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2863-8132","authenticated-orcid":false,"given":"Rebecca L.","family":"McIntyre","sequence":"first","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases Amsterdam Gastroenterology, Endocrinology, and Metabolism Amsterdam Cardiovascular Sciences 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