A Possible Reason For Sirtuin Uncertainty

While sirtuins extend life in lower animals, manipulation of sirtuins in mammals hasn't produced the sort of enhanced longevity seen in other genetic engineering techniques, or even just plain old calorie restriction. Here, a reason is suggested: "Sir2 mediates lifespan extension in lower eukaryotes but whether its mammalian 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 [with] strikingly lengthened replicative lifespan. Thus, SIRT1 can markedly postpone SMC senescence, but this requires overcoming otherwise vulnerable NAD(+) salvage in aging SMCs." With the caution that results in cells are not results in whole animals, you might want to take a look at the role of NAD+ in cells. It is part of a cycling mechanism of metabolism that can cause all sorts of issues if disrupted.

Link: http://www.ncbi.nlm.nih.gov/pubmed/19716821

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