論文 - 詳細
| RRC ID | 46596 |
|---|---|
| 著者 | Goudeau J, Bellemin S, Toselli-Mollereau E, Shamalnasab M, Chen Y, Aguilaniu H. |
| タイトル | Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans. |
| ジャーナル | PLoS Biol |
| 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. |
| 巻・号 | 9(3) |
| ページ | e1000599 |
| 公開日 | 2011-3-1 |
| DOI | 10.1371/journal.pbio.1000599 |
| PMID | 21423649 |
| PMC | PMC3057950 |
| MeSH | Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Fatty Acids / chemistry* Fatty Acids / metabolism* Germ Cells / cytology Germ Cells / physiology* Longevity* Oleic Acid / metabolism Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Recombinant Fusion Proteins / metabolism Signal Transduction Stearoyl-CoA Desaturase / metabolism |
| IF | 7.076 |
| 引用数 | 97 |
| WOS 分野 | BIOLOGY BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| 線虫 | tm1011 tm331 tm420 |