RRC ID 51360
Author Han S, Schroeder EA, Silva-García CG, Hebestreit K, Mair WB, Brunet A.
Title Mono-unsaturated fatty acids link H3K4me3 modifiers to C. elegans lifespan.
Journal 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.
Volume 544(7649)
Pages 185-190
Published 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
Times Cited 75
C.elegans tm1011 tm1231 tm2182 tm331 tm420