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. 2012 Oct 31;3(4):e0022.
doi: 10.5041/RMMJ.10093. Print 2012 Oct.

The Contentious History of Sirtuin Debates

Free PMC article

The Contentious History of Sirtuin Debates

Shoshana Naiman et al. Rambam Maimonides Med J. .
Free PMC article


The sirtuins are highly conserved enzyme homologues of the yeast Sir2, with activities of NAD+ dependent deacetylase and/or mono ADP ribosyltransferase. A long line of evidence has implicated sirtuins in regulating the aging process of yeast, worms, flies, and rodents. Moreover, much work has been published on the important role of sirtuins in several age-related diseases such as diabetes type II, cancer, cardiovascular diseases, and dyslipidemia. However, despite the many publications supporting a pro-longevity role for sirtuins, there has been emerging debate about the direct role of Caenorhabditis elegans and Drosophila melanogaster sirtuins in aging and in lifespan extension in response to dietary restriction. In addition, until recently, the role of the seven mammalian sirtuins, SIRT1 to SIRT7, in regulating lifespan was unclear. Here, we review the history of the scientific debate on the role of sirtuins in regulating lifespan, especially in light of a recent publication showing a direct regulation of mammalian lifespan by a sirtuin family member, SIRT6.

Keywords: Aging; SIRT6; Sir2; deacetylation; dietary restriction; sirtuins.


Figure 1
Figure 1
The history of the debate on the role of sirtuins in regulating lifespan. DR, dietary restriction; ERC, extrachromosomal rDNA circle; Sir, silent information regulator; SIRT, sirtuin.

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