Authors: Goudeau, Jerome; Bellemin, Stephanie; Toselli-Mollereau, Esther; Shamalnasab, Mehrnaz; Chen, Yiqun; Aguilaniu, Hugo
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. 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.
Keywords: Animals; Caenorhabditis elegans/cytology/*physiology; Caenorhabditis elegans Proteins/genetics/*metabolism; Fatty Acids/*chemistry/*metabolism; Germ Cells/cytology/*physiology; *Longevity; Oleic Acid/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism; Recombinant Fusion Proteins/metabolism; Signal Transduction; Stearoyl-CoA Desaturase/metabolism|
Journal: PLoS Biol Volume: 9 Issue: 3 Pages: e1000599 Date: March 23, 2011 PMID: 21423649 |
Goudeau, Jerome, Bellemin, Stephanie, Toselli-Mollereau, Esther, Shamalnasab, Mehrnaz, Chen, Yiqun, Aguilaniu, Hugo (2011) Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans. PLoS Biol 9: e1000599.
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