NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory < i > C. elegans < /i > mutants

Longevity is often associated with stress resistance, but whether they are causally linked is incompletely understood. Here we investigate chemosensory defectiveCaenorhabditis elegans mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein geneosm-3 were significantly protected from tunicamycin-induced ER stress. Whileosm-3 lifespan extension is dependent on the key longevity factor DAF-16/FOXO, tunicamycin resistance was not.osm-3 mutants are protected from bacterial pathogens, which ispmk-1 p38 MAP kinase dependent while TM resistance waspmk-1 independent. Expression of P-glycoprotein (PGP) xenobiotic detoxification genes was elevated inosm-3 mutants and their knockdown or inhibition with verapamil suppressed tunicamycin resistance. The nuclear hormone receptornhr-8 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 inosm-3 mutants.
Source: eLife - Category: Biomedical Science Tags: Genetics and Genomics Source Type: research