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

Longevity is often associated with stress resistance, but whether they are causally linked is incompletely understood. Here we investigate chemosensory-defective Caenorhabditis elegans mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein gene...

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Autores principales:	Gabriel A Guerrero, Maxime J Derisbourg, Felix AMC Mayr, Laura E Wester, Marco Giorda, J Eike Dinort, Matías D Hartman, Klara Schilling, María José Alonso-De Gennaro, Ryan J Lu, Bérénice A Benayoun, Martin S Denzel
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	longevity aging chemosensory mutants xenobiotic detoxification Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b5da5aa2ccee4aeda56385feab2e8031
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spelling	oai:doaj.org-article:b5da5aa2ccee4aeda56385feab2e80312021-11-08T11:59:35ZNHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants10.7554/eLife.531742050-084Xe53174https://doaj.org/article/b5da5aa2ccee4aeda56385feab2e80312021-08-01T00:00:00Zhttps://elifesciences.org/articles/53174https://doaj.org/toc/2050-084XLongevity is often associated with stress resistance, but whether they are causally linked is incompletely understood. Here we investigate chemosensory-defective Caenorhabditis elegans mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein gene osm-3 were significantly protected from tunicamycin-induced ER stress. While osm-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 is pmk-1 p38 MAP kinase dependent, while TM resistance was pmk-1 independent. Expression of P-glycoprotein (PGP) xenobiotic detoxification genes was elevated in osm-3 mutants and their knockdown or inhibition with verapamil suppressed tunicamycin resistance. The nuclear hormone receptor nhr-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 in osm-3 mutants.Gabriel A GuerreroMaxime J DerisbourgFelix AMC MayrLaura E WesterMarco GiordaJ Eike DinortMatías D HartmanKlara SchillingMaría José Alonso-De GennaroRyan J LuBérénice A BenayounMartin S DenzeleLife Sciences Publications Ltdarticlelongevityagingchemosensory mutantsxenobiotic detoxificationMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	longevity aging chemosensory mutants xenobiotic detoxification Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	longevity aging chemosensory mutants xenobiotic detoxification Medicine R Science Q Biology (General) QH301-705.5 Gabriel A Guerrero Maxime J Derisbourg Felix AMC Mayr Laura E Wester Marco Giorda J Eike Dinort Matías D Hartman Klara Schilling María José Alonso-De Gennaro Ryan J Lu Bérénice A Benayoun Martin S Denzel NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
description	Longevity is often associated with stress resistance, but whether they are causally linked is incompletely understood. Here we investigate chemosensory-defective Caenorhabditis elegans mutants that are long-lived and stress resistant. We find that mutants in the intraflagellar transport protein gene osm-3 were significantly protected from tunicamycin-induced ER stress. While osm-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 is pmk-1 p38 MAP kinase dependent, while TM resistance was pmk-1 independent. Expression of P-glycoprotein (PGP) xenobiotic detoxification genes was elevated in osm-3 mutants and their knockdown or inhibition with verapamil suppressed tunicamycin resistance. The nuclear hormone receptor nhr-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 in osm-3 mutants.
format	article
author	Gabriel A Guerrero Maxime J Derisbourg Felix AMC Mayr Laura E Wester Marco Giorda J Eike Dinort Matías D Hartman Klara Schilling María José Alonso-De Gennaro Ryan J Lu Bérénice A Benayoun Martin S Denzel
author_facet	Gabriel A Guerrero Maxime J Derisbourg Felix AMC Mayr Laura E Wester Marco Giorda J Eike Dinort Matías D Hartman Klara Schilling María José Alonso-De Gennaro Ryan J Lu Bérénice A Benayoun Martin S Denzel
author_sort	Gabriel A Guerrero
title	NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
title_short	NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
title_full	NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
title_fullStr	NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
title_full_unstemmed	NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants
title_sort	nhr-8 and p-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory c. elegans mutants
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/b5da5aa2ccee4aeda56385feab2e8031
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NHR-8 and P-glycoproteins uncouple xenobiotic resistance from longevity in chemosensory C. elegans mutants

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