Title
SIRT1 Markedly Extends Replicative Lifespan if the NAD+ Salvage Pathway Is Enhanced
Document Type
Article
Publication Date
9-17-2009
Journal
FEBS Letters
Volume
583
Issue
18
First Page
3081
Last Page
3085
URL with Digital Object Identifier
10.1016/j.febslet.2009.08.031
Abstract
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.
