Document Detail

Regulation of fatty acid synthesis and Delta9-desaturation in senescence of human fibroblasts.
MedLine Citation:
PMID:  19059270     Owner:  NLM     Status:  MEDLINE    
AIMS: Normal human cells in culture progressively lose their capacity for replication, ending in an irreversible arrested state known as replicative senescence. Senescence has been functionally associated to the process of organismal ageing and is also considered a major tumor-suppressing mechanism. Although a great deal of knowledge has uncovered many of the molecular aspects of senescence, little is known about the regulation of lipid synthesis, particularly the biosynthesis and Delta9-desaturation of fatty acids, during the senescence process.
MAIN METHODS: By using immunoblotting and metabolic radiolabeling, we determined the senescence-associated changes in major lipogenic pathways.
KEY FINDINGS: The levels of fatty acid synthase and stearoyl-CoA desaturase-1 and, consequently, the formation of monounsaturated fatty acids, were notably decreased in senescent cells when compared to proliferating (young) fibroblasts. Moreover, we detected a reduction in the de novo synthesis of phospholipids with a concomitant increase in the formation of cholesterol in senescent cells compared to young fibroblasts. Finally, it was found that exogenous fatty acids were preferentially incorporated into the triacylglycerol pool of senescent cells.
SIGNIFICANCE: This set of observations is the first demonstration of a profound modification in lipid metabolism, particularly fatty acid biosynthesis and desaturation, caused by the senescence process and contributes to the increasing body of evidence linking de novo lipogenesis with cellular proliferation.
Miho Maeda; Natalia Scaglia; R Ariel Igal
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-27
Journal Detail:
Title:  Life sciences     Volume:  84     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-05     Completed Date:  2009-03-10     Revised Date:  2012-05-24    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  119-24     Citation Subset:  IM    
Department of Nutritional Sciences and Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
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MeSH Terms
Cell Aging*
Cells, Cultured
Fatty Acid Desaturases / analysis*
Fatty Acid Synthetase Complex / analysis*
Fatty Acids / biosynthesis*
Fibroblasts / cytology,  metabolism*
Oleic Acid / pharmacology
Stearoyl-CoA Desaturase / analysis*
Reg. No./Substance:
0/Fatty Acids; 112-80-1/Oleic Acid; EC 1.14.19.-/Fatty Acid Desaturases; EC protein, human; EC Desaturase; EC 1.14.99.-/delta-9 fatty acid desaturase; EC 6.-/Fatty Acid Synthetase Complex

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