Journal
FEBS LETTERS
Volume 583, Issue 18, Pages 3081-3085Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2009.08.031
Keywords
Vascular smooth muscle; Senescence; SIRT1; NAD(+) salvage; Nampt
Funding
- Heart and Stroke Foundation of Ontario [HSFO T5675, PRG4854]
- Canadian Institutes of Health Research [FRN-11715]
- Krembil Foundation
- HSFO Career Investigator Award
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Sir2 mediates lifespan extension in lower eukaryotes but whether its mammalian homolog, sirtuin 1, silent mating type information regulation 2 homolog (SIRT1), is a longevity protein is controversial. We stably introduced the SIRT1 gene into human vascular smooth muscle cells (SMCs) and observed minimal extension of replicative lifespan. However, SIRT1 activity was found to be exquisitely dependent on nicotinamide phosphoribosyltransferase (Nampt) activity. Moreover, overexpression of Nampt converted SIRT1-overexpressing SMCs to senescence-resistant cells together with heightened SIRT1 activity, suppressed p21, and strikingly lengthened replicative lifespan. Thus, SIRT1 can markedly postpone SMC senescence, but this requires overcoming an otherwise vulnerable nicotinamide adenine dinucleotide salvage reaction in aging SMCs. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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