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Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans

BACKGROUND: Preventing germline stem cell proliferation extends lifespan in nematodes and flies. So far, studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR. Here, we report on NHR-80/HNF4, a nuclear receptor that specifically mediates longevity induced by depletion of...

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Autores principales: Goudeau, Jérôme, Bellemin, Stéphanie, Toselli-Mollereau, Esther, Shamalnasab, Mehrnaz, Chen, Yiqun, Aguilaniu, Hugo
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057950/
https://www.ncbi.nlm.nih.gov/pubmed/21423649
http://dx.doi.org/10.1371/journal.pbio.1000599
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author Goudeau, Jérôme
Bellemin, Stéphanie
Toselli-Mollereau, Esther
Shamalnasab, Mehrnaz
Chen, Yiqun
Aguilaniu, Hugo
author_facet Goudeau, Jérôme
Bellemin, Stéphanie
Toselli-Mollereau, Esther
Shamalnasab, Mehrnaz
Chen, Yiqun
Aguilaniu, Hugo
author_sort Goudeau, Jérôme
collection PubMed
description BACKGROUND: Preventing germline stem cell proliferation extends lifespan in nematodes and flies. So far, studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR. Here, we report on NHR-80/HNF4, a nuclear receptor that specifically mediates longevity induced by depletion of the germ line through a mechanism that implicates fatty acid monodesaturation. METHODS AND FINDINGS: nhr-80/HNF4 is induced in animals lacking a germ line and is specifically required for their extended longevity. Overexpressing nhr-80/HNF4 increases the lifespan of germline-less animals. This lifespan extension can occur in the absence of daf-16/FOXO but requires the presence of the nuclear receptor DAF-12/VDR. We show that the fatty acid desaturase, FAT-6/SCD1, is a key target of NHR-80/HNF4 and promotes germline-longevity by desaturating stearic acid to oleic acid (OA). We find that NHR-80/HNF4 and OA must work in concert to promote longevity. CONCLUSIONS: Taken together, our data indicate that the NHR-80 pathway participates in the mechanism of longevity extension through depletion of the germ line. We identify fat-6 and OA as essential downstream elements although other targets must also be present. Thus, NHR-80 links fatty acid desaturation to lifespan extension through germline ablation in a daf-16/FOXO independent manner.
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spelling pubmed-30579502011-03-21 Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans Goudeau, Jérôme Bellemin, Stéphanie Toselli-Mollereau, Esther Shamalnasab, Mehrnaz Chen, Yiqun Aguilaniu, Hugo PLoS Biol Research Article BACKGROUND: Preventing germline stem cell proliferation extends lifespan in nematodes and flies. So far, studies on germline-longevity signaling have focused on daf-16/FOXO and daf-12/VDR. Here, we report on NHR-80/HNF4, a nuclear receptor that specifically mediates longevity induced by depletion of the germ line through a mechanism that implicates fatty acid monodesaturation. METHODS AND FINDINGS: nhr-80/HNF4 is induced in animals lacking a germ line and is specifically required for their extended longevity. Overexpressing nhr-80/HNF4 increases the lifespan of germline-less animals. This lifespan extension can occur in the absence of daf-16/FOXO but requires the presence of the nuclear receptor DAF-12/VDR. We show that the fatty acid desaturase, FAT-6/SCD1, is a key target of NHR-80/HNF4 and promotes germline-longevity by desaturating stearic acid to oleic acid (OA). We find that NHR-80/HNF4 and OA must work in concert to promote longevity. CONCLUSIONS: Taken together, our data indicate that the NHR-80 pathway participates in the mechanism of longevity extension through depletion of the germ line. We identify fat-6 and OA as essential downstream elements although other targets must also be present. Thus, NHR-80 links fatty acid desaturation to lifespan extension through germline ablation in a daf-16/FOXO independent manner. Public Library of Science 2011-03-15 /pmc/articles/PMC3057950/ /pubmed/21423649 http://dx.doi.org/10.1371/journal.pbio.1000599 Text en Goudeau et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Goudeau, Jérôme
Bellemin, Stéphanie
Toselli-Mollereau, Esther
Shamalnasab, Mehrnaz
Chen, Yiqun
Aguilaniu, Hugo
Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans
title Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans
title_full Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans
title_fullStr Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans
title_full_unstemmed Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans
title_short Fatty Acid Desaturation Links Germ Cell Loss to Longevity Through NHR-80/HNF4 in C. elegans
title_sort fatty acid desaturation links germ cell loss to longevity through nhr-80/hnf4 in c. elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3057950/
https://www.ncbi.nlm.nih.gov/pubmed/21423649
http://dx.doi.org/10.1371/journal.pbio.1000599
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