Regulation of fatty acid synthesis and Delta9-desaturation in senescence of human fibroblasts.
OBJECTIVE
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.


METHODS
By using immunoblotting and metabolic radiolabeling, we determined the senescence-associated changes in major lipogenic pathways.


RESULTS
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.


CONCLUSIONS
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.
Maeda
Miho
M
Department of Nutritional Sciences and Rutgers Center for Lipid Research, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Scaglia
Natalia
N
Igal
R Ariel
RA
D002478:Cells, Cultured; D016922:Cellular Senescence; D044943:Fatty Acid Desaturases / Q000032:analysis*; D064429:Fatty Acid Synthases / Q000032:analysis*; D005227:Fatty Acids / Q000096:biosynthesis*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D019301:Oleic Acid / Q000494:pharmacology; D013230:Stearoyl-CoA Desaturase / Q000032:analysis*
D005227:Fatty Acids; D019301:Oleic Acid; D044943:Fatty Acid Desaturases; C523776:SCD1 protein, human; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase; D064429:Fatty Acid Synthases