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Here we investigate chemosensory-defective\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein gene\n                    <jats:italic>osm-3<\/jats:italic>\n                    were significantly protected from tunicamycin-induced ER stress. While\n                    <jats:italic>osm-3<\/jats:italic>\n                    lifespan extension is dependent on the key longevity factor DAF-16\/FOXO, tunicamycin resistance was not.\n                    <jats:italic>osm-3<\/jats:italic>\n                    mutants are protected from bacterial pathogens, which is\n                    <jats:italic>pmk-1<\/jats:italic>\n                    p38 MAP kinase dependent, while TM resistance was\n                    <jats:italic>pmk-1<\/jats:italic>\n                    independent. Expression of P-glycoprotein (PGP) xenobiotic detoxification genes was elevated in\n                    <jats:italic>osm-3<\/jats:italic>\n                    mutants and their knockdown or inhibition with verapamil suppressed tunicamycin resistance. The nuclear hormone receptor\n                    <jats:italic>nhr-8<\/jats:italic>\n                    was necessary to regulate a subset of PGPs. We thus identify a cell-nonautonomous regulation of xenobiotic detoxification and show that separate pathways are engaged to mediate longevity, pathogen resistance, and xenobiotic detoxification in\n                    <jats:italic>osm-3<\/jats:italic>\n                    mutants.\n                  <\/jats:p>","DOI":"10.7554\/elife.53174","type":"journal-article","created":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T08:01:42Z","timestamp":1630051302000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.53174","source":"Crossref","is-referenced-by-count":21,"title":["NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants"],"prefix":"10.7554","volume":"10","author":[{"given":"Gabriel A","family":"Guerrero","sequence":"first","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9293-1413","authenticated-orcid":true,"given":"Maxime J","family":"Derisbourg","sequence":"first","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix AMC","family":"Mayr","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura E","family":"Wester","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Giorda","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Eike","family":"Dinort","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mat\u00edas D","family":"Hartman","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klara","family":"Schilling","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Alonso-De Gennaro","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing","place":["Cologne, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J","family":"Lu","sequence":"additional","affiliation":[{"name":"Leonard Davis School of Gerontology, University of 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