{"doi":"10.1101/2020.07.24.219584","title":"Inhibition of the neuromuscular acetylcholine receptor with atracurium activates FOXO/DAF-16-induced longevity","abstract":"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 C. elegans . This longevity is dependent on both daf-16 signaling and inhibition of the neuromuscular acetylcholine receptor. Other neuromuscular blockers tubocurarine and pancuronium caused similar healthspan benefits. We demonstrate nuclear localization of DAF-16 upon atracurium treatment, and, using RNAseq transcriptomics, identify 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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123898,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9542,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":568101,"name":"Simone Denis","orcid":null,"position":1,"is_corresponding":false},{"id":568102,"name":"Rashmi Kamble","orcid":null,"position":2,"is_corresponding":false},{"id":291048,"name":"Michael Petr","orcid":"0000-0002-1808-0163","position":3,"is_corresponding":false},{"id":267060,"name":"Bauke V. Schomakers","orcid":"0000-0002-0242-9113","position":4,"is_corresponding":false},{"id":267055,"name":"Aldo Jongejan","orcid":"0000-0002-8948-2549","position":5,"is_corresponding":false},{"id":228955,"name":"Morten Scheibye‐Knudsen","orcid":"0000-0002-6637-1280","position":6,"is_corresponding":false},{"id":267066,"name":"Riekelt H. Houtkooper","orcid":"0000-0001-9961-0842","position":7,"is_corresponding":false},{"id":267053,"name":"Georges E. Janssens","orcid":"0000-0003-2104-8145","position":8,"is_corresponding":false},{"id":353004,"name":"Rebecca L. McIntyre","orcid":"0000-0002-2863-8132","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}