title: Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Ecole normale supérieure de Lyon-CNRS-Université de Lyon Claude Bernard, Molecular Biology of the Cell Laboratory/UMR5239, Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Goudeau
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bellemin
authors.forename: Esther
authors.initials: E
authors.lastname: Toselli-Mollereau
authors.forename: Mehrnaz
authors.initials: M
authors.lastname: Shamalnasab
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Chen
authors.forename: Hugo
authors.initials: H
authors.lastname: Aguilaniu
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000737:chemistry* / Q000378:metabolism*; D005854:Germ Cells / Q000166:cytology / Q000502:physiology*; D008136:Longevity; D019301:Oleic Acid / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D005227:Fatty Acids; C559127:NHR-80 protein, C elegans; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D019301:Oleic Acid; D013230:Stearoyl-CoA Desaturase