Sterol Regulatory Element-binding Protein (SREBP)-1-mediated lipogenesis is involved in cell senescence

You Mie Kim, Hyun Taek Shin, Yong Hak Seo, Hae Ok Byun, Soo Han Yoon, In Kyu Lee, Dong Hoon Hyun, Hae Young Chung, Gyesoon Yoon

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73 Scopus citations


Increased cell mass is one of the characteristics of senescent cells, but this event has not been clearly defined. When subcellular organellar mass was estimated with organelle-specific fluorescence dyes, we observed that most membranous organelles progressively increase in mass during cell senescence. This increase was accompanied by an increase in membrane lipids and augmented expression of lipogenic enzymes, such as fatty acid synthase (FAS), ATP citrate lyase, and acetyl-CoA carboxylase. The mature form of sterol regulatory element-binding protein (SREBP)-1 was also elevated. Increased expression of these lipogenic effectors was further observed in the liver tissues of aging Fischer 344 rats. Ectopic expression of mature form of SREBP-1 in both Chang cells and primary young human diploid fibroblasts was enough to induce senescence. Blocking lipogenesis with FAS inhibitors (cerulenin and C75) and via siRNA-mediated silencing of SREBP-1 and ATP citrate lyase significantly attenuated H2O2-induced senescence. Finally, old human diploid fibroblasts were effectively reversed to young-like cells by challenging with FAS inhibitors. Our results suggest that enhanced lipogenesis is not only a common event, but also critically involved in senescence via SREBP-1 induction, thereby contributing to the increase in organelle mass (as a part of cell mass), a novel indicator of senescence.

Original languageEnglish
Pages (from-to)29069-29077
Number of pages9
JournalJournal of Biological Chemistry
Issue number38
StatePublished - 17 Sep 2010


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