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SIRT1 markedly extends replicative lifespan if the NAD + salvage pathway is enhanced
Author(s) -
Ho Cynthia,
van der Veer Eric,
Akawi Oula,
Pickering J. Geoffrey
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.08.031
Subject(s) - nicotinamide phosphoribosyltransferase , nad+ kinase , sirtuin 1 , sirtuin , senescence , longevity , nicotinamide adenine dinucleotide , nucleotide salvage , biology , microbiology and biotechnology , nicotinamide mononucleotide , gene silencing , gene , sirt6 , chemistry , biochemistry , enzyme , genetics , downregulation and upregulation , nucleotide
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.