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PMID: 18988854 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Fat metabolism links germline stem cells and longevity in C. elegans.

Science (New York, N.Y.) ·Vol. 322 ·No. 5903 ·2008-11-07 ·Pages 957-60

Wang MC, O'Rourke EJ, Ruvkun G

Abstract

Fat metabolism, reproduction, and aging are intertwined regulatory axes; however, the mechanism by which they are coupled remains poorly understood. We found that germline stem cells (GSCs) actively modulate lipid hydrolysis in Caenorhabditis elegans, which in turn regulates longevity. GSC arrest promotes systemic lipolysis via induction of a specific fat lipase. Subsequently, fat mobilization is promoted and life span is prolonged. Constitutive expression of this lipase in fat storage tissue generates lean and long-lived animals. This lipase is a key factor in the lipid hydrolysis and increased longevity that are induced by decreased insulin signaling. These results suggest a link between C. elegans fat metabolism and longevity.

MeSH Terms
Aging Animals Caenorhabditis elegans/genetics,metabolism,physiology Caenorhabditis elegans Proteins/genetics,metabolism Cell Differentiation Cell Proliferation Forkhead Transcription Factors Genes, Helminth Germ Cells/cytology,metabolism Hydrolysis Intestinal Mucosa/metabolism Intestines/cytology Intracellular Signaling Peptides and Proteins/metabolism Lipase/genetics,metabolism Lipid Metabolism Longevity Models, Animal Receptor, Insulin/metabolism Reproduction Signal Transduction Stem Cells/cytology,metabolism Temperature Transcription Factors/metabolism
Chemicals
Caenorhabditis elegans Proteins Forkhead Transcription Factors Intracellular Signaling Peptides and Proteins KRI-1 protein, C elegans Transcription Factors daf-16 protein, C elegans DAF-2 protein, C elegans Receptor, Insulin Lipase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wang Meng C
Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston, MA 02114, USA.
O'Rourke Eyleen J
Ruvkun Gary
References (24)
24 references, click to expand
  1. IRS-2 pathways integrate female reproduction and energy homeostasis.
    Nature. 2000 Sep 21;407(6802):377-82 PMID: 11014193
  2. Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling.
    Cell. 2006 Mar 10;124(5):1055-68 PMID: 16530050
  3. Regulation of C. elegans life-span by insulinlike signaling in the nervous system.
    Science. 2000 Oct 6;290(5489):147-50 PMID: 11021802
  4. Regulation of life-span by germ-line stem cells in Caenorhabditis elegans.
    Science. 2002 Jan 18;295(5554):502-5 PMID: 11799246
  5. Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes.
    Nature. 2003 Jan 16;421(6920):268-72 PMID: 12529643
  6. Extended longevity in mice lacking the insulin receptor in adipose tissue.
    Science. 2003 Jan 24;299(5606):572-4 PMID: 12543978
  7. Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition.
    Genetics. 2003 Jan;163(1):115-32 PMID: 12586701
  8. DAF-16 target genes that control C. elegans life-span and metabolism.
    Science. 2003 Apr 25;300(5619):644-7 PMID: 12690206
  9. The emergence of the metabolic syndrome with menopause.
    J Clin Endocrinol Metab. 2003 Jun;88(6):2404-11 PMID: 12788835
  10. Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body.
    Nature. 2004 Jun 3;429(6991):562-6 PMID: 15175753
  11. Long-lived Drosophila with overexpressed dFOXO in adult fat body.
    Science. 2004 Jul 16;305(5682):361 PMID: 15192154
  12. On the control of germ cell development in Caenorhabditis elegans.
    Dev Biol. 1981 Jan 30;81(2):208-19 PMID: 7202837
  13. Sex determination in the nematode C. elegans: analysis of tra-3 suppressors and characterization of fem genes.
    Genetics. 1986 Sep;114(1):15-52 PMID: 3770465
  14. Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans.
    Genetics. 1987 Jan;115(1):107-19 PMID: 3557107
  15. The glp-1 locus and cellular interactions in early C. elegans embryos.
    Cell. 1987 Nov 20;51(4):601-11 PMID: 3677169
  16. Characterization of a germ-line proliferation mutation in C. elegans.
    Development. 1992 Nov;116(3):755-66 PMID: 1289064
  17. Analysis of the multiple roles of gld-1 in germline development: interactions with the sex determination cascade and the glp-1 signaling pathway.
    Genetics. 1995 Feb;139(2):607-30 PMID: 7713420
  18. lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans.
    Development. 1994 Oct;120(10):2913-24 PMID: 7607081
  19. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans.
    Nature. 1997 Oct 30;389(6654):994-9 PMID: 9353126
  20. An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans.
    Genetics. 1998 Feb;148(2):703-17 PMID: 9504918
  21. Lipolysis: pathway under construction.
    Curr Opin Lipidol. 2005 Jun;16(3):333-40 PMID: 15891395
  22. Molecular mechanisms of germline stem cell regulation.
    Annu Rev Genet. 2005;39:173-95 PMID: 16285857
  23. Polygenic control of Caenorhabditis elegans fat storage.
    Nat Genet. 2006 Mar;38(3):363-8 PMID: 16462744
  24. SMK-1, an essential regulator of DAF-16-mediated longevity.
    Cell. 2006 Mar 10;124(5):1039-53 PMID: 16530049
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1162011
Published
2008-11-07
Pages
957-60
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC2760269
Subset
IM
Grants
NIA NIH HHS · R01 AG016636 · United States
NIA NIH HHS · R37 AG014161 · United States
NIA NIH HHS · R37 AG014161-13 · United States
NIA NIH HHS · 5R01AG016636 · United States
NIA NIH HHS · R01 AG016636-10 · United States
Corrections
CommentIn
PMID: 18988829
External Links
PubMed source DOI: 10.1126/science.1162011 PMC Full Text View journal details
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