Impact of Sirt1 on mammalian aging

Abstract

Studies in yeast, flies and worms have indicated that overexpression of the protein deacetylase Sir2 increases longevity [1]. Mammals possess 7 paralogs of the Sir2 gene, being Sirt1 the most similar one closest to Sir2 [1]. In our recent work [2], we have used a genetic approach to address the effect of Sirt1 on mammalian ageing. In particular, we have generated two independent lines of transgenic mice that globally overexpress Sirt1 (≈3-fold) under the control of its own regulatory elements (Sirt1-tg mice). Previously, we had shown that these Sirt1-tg mice are protected from the metabolic damage associated to high-fat diet (HFD) through the inhibition of NFκB inflammatory pathway and the activation of PGC1α antioxidant response [3]. The potent beneficial effects of Sirt1 in protecting from metabolic syndrome and its associated pathologies, such as diabetes and fatty liver, have consistently emerged in a variety of mouse models as one of the main physiological activities of Sirt1 [3-7]. We now report the ageing and longevity of Sirt1-tg mice [2].