Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans

• Published in: PLoS biology 2011-03, Vol.9 (3), p.e1000599-e1000599
• Main Authors: Goudeau, Jérôme, Bellemin, Stéphanie, Toselli-Mollereau, Esther, Shamalnasab, Mehrnaz, Chen, Yiqun, Aguilaniu, Hugo
• Format: Article
• Language: English
• Subjects: Animals; Caenorhabditis elegans; Caenorhabditis elegans - cytology; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell division; Cell proliferation; Chemical properties; Development Biology; Developmental Biology/Aging; Experiments; Fatty acids; Fatty Acids - chemistry; Fatty Acids - metabolism; Genetic aspects; Genetics; Germ Cells - cytology; Germ Cells - physiology; Insects; Insulin; Life Sciences; Longevity; Oleic Acid - metabolism; Proteins; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Recombinant Fusion Proteins - metabolism; Signal Transduction; Stearoyl-CoA Desaturase - metabolism; Stem cells
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.1000599

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. 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. 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.