SIRT1 markedly extends replicative lifespan if the NAD+ salvage pathway is enhanced
SIRT1 markedly extends replicative lifespan if the NAD+ salvage pathway is enhanced
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DOI：
10.1016/j.febslet.2009.08.031
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发表时间：
2009-09-17
期刊：
影响因子：
3.5
通讯作者：
Pickering, J. Geoffrey
中科院分区：
文献类型：
--
作者：
Ho, Cynthia;van der Veer, Eric;Pickering, J. Geoffrey
sirr2在低等真核生物中介导寿命延长，但其在哺乳动物中的同源物sirtuin 1，即沉默交配型信息调节2同源物（SIRT1）是否是一种长寿蛋白还存在争议。我们稳定地将SIRT1基因引入人血管平滑肌细胞（SMCs），并观察到复制寿命的最小延长。然而，SIRT1活性被发现非常依赖于烟酰胺磷酸核糖基转移酶（Nampt）活性。此外，Nampt的过表达将SIRT1过表达的SMCs转化为抗衰老细胞，同时SIRT1活性升高，p21受到抑制，并显著延长了复制寿命。因此，SIRT1可以显著延缓SMC衰老，但这需要克服老化SMC中脆弱的烟酰胺腺嘌呤二核苷酸挽救反应。(C) 2009年欧洲生化学会联合会。Elsevier b.v.版权所有。
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.