論文 - 詳細
RRC ID | 51360 |
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著者 | Han S, Schroeder EA, Silva-García CG, Hebestreit K, Mair WB, Brunet A. |
タイトル | Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan. |
ジャーナル | Nature |
Abstract |
Chromatin and metabolic states both influence lifespan, but how they interact in lifespan regulation is largely unknown. The COMPASS chromatin complex, which trimethylates lysine 4 on histone H3 (H3K4me3), regulates lifespan in Caenorhabditis elegans. However, the mechanism by which H3K4me3 modifiers affect longevity, and whether this mechanism involves metabolic changes, remain unclear. Here we show that a deficiency in H3K4me3 methyltransferase, which extends lifespan, promotes fat accumulation in worms with a specific enrichment of mono-unsaturated fatty acids (MUFAs). This fat metabolism switch in H3K4me3 methyltransferase-deficient worms is mediated at least in part by the downregulation of germline targets, including S6 kinase, and by the activation of an intestinal transcriptional network that upregulates delta-9 fatty acid desaturases. Notably, the accumulation of MUFAs is necessary for the lifespan extension of H3K4me3 methyltransferase-deficient worms, and dietary MUFAs are sufficient to extend lifespan. Given the conservation of lipid metabolism, dietary or endogenous MUFAs could extend lifespan and healthspan in other species, including mammals. |
巻・号 | 544(7649) |
ページ | 185-190 |
公開日 | 2017-4-13 |
DOI | 10.1038/nature21686 |
PMID | 28379943 |
PMC | PMC5391274 |
MeSH | Aging / drug effects Aging / metabolism Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Dietary Fats / administration & dosage Dietary Fats / metabolism Dietary Fats / pharmacology* Down-Regulation Fatty Acid Desaturases / genetics Fatty Acid Desaturases / metabolism Fatty Acids, Unsaturated / administration & dosage Fatty Acids, Unsaturated / metabolism* Fatty Acids, Unsaturated / pharmacology Gene Expression Regulation, Enzymologic Germ Cells / enzymology Germ Cells / metabolism Histone-Lysine N-Methyltransferase / deficiency Histone-Lysine N-Methyltransferase / metabolism Histones / chemistry Histones / metabolism* Intestinal Mucosa / metabolism Intestines / enzymology Lipid Metabolism / drug effects Longevity / drug effects* Longevity / physiology* Lysine / metabolism* Methylation Ribosomal Protein S6 Kinases, 70-kDa / deficiency Ribosomal Protein S6 Kinases, 70-kDa / metabolism Stearoyl-CoA Desaturase Up-Regulation |
IF | 42.779 |
引用数 | 75 |
リソース情報 | |
線虫 | tm1011 tm1231 tm2182 tm331 tm420 |