The sirtuin SIRT6 regulates lifespan in male mice
The sirtuin SIRT6 regulates lifespan in male mice
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DOI：
10.1038/nature10815
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发表时间：
2012-03-08
期刊：
影响因子：
64.8
通讯作者：
Cohen, Haim Y.
中科院分区：
文献类型：
--
作者：
Kanfi, Yariv;Naiman, Shoshana;Cohen, Haim Y.
在过去的一个世纪里，人类寿命的显著增加给我们带来了巨大的医疗挑战。为了应对这些挑战，必须了解和控制决定健康老龄化的机制。Sirtuins是高度保守的去乙酰化酶，已被证明可以调节酵母、线虫和果蝇的寿命(1)。然而，sirtuins在调节蠕虫和苍蝇寿命中的作用最近引起了争议(2)。此外，SIRT1至SIRT7（酵母sirtuin Sir2的同源物）这7种哺乳动物sirtuin在调节寿命中的作用尚不清楚(3)。在这里，我们发现过表达Sirt6的雄性而非雌性转基因小鼠的寿命明显长于野生型小鼠（参考文献4）。基因表达分析显示，雄性sirt6转基因小鼠与雄性野生型小鼠之间存在显著差异：转基因雄性血清中胰岛素样生长因子1 （IGF1）水平较低，igf结合蛋白1水平较高，IGF1信号传导主要组分磷酸化水平发生改变，而IGF1信号传导是调节寿命的关键途径(5)。这项研究表明sirtuin家族成员对哺乳动物寿命的调节，对年龄相关疾病的治疗具有重要意义。
The significant increase in human lifespan during the past century confronts us with great medical challenges. To meet these challenges, the mechanisms that determine healthy ageing must be understood and controlled. Sirtuins are highly conserved deacetylases that have been shown to regulate lifespan in yeast, nematodes and fruitflies(1). However, the role of sirtuins in regulating worm and fly lifespan has recently become controversial(2). Moreover, the role of the seven mammalian sirtuins, SIRT1 to SIRT7 (homologues of the yeast sirtuin Sir2), in regulating lifespan is unclear(3). Here we show that male, but not female, transgenic mice overexpressing Sirt6 (ref. 4) have a significantly longer lifespan than wild-type mice. Gene expression analysis revealed significant differences between male Sirt6-transgenic mice and male wild-type mice: transgenic males displayed lower serum levels of insulin-like growth factor 1 (IGF1), higher levels of IGF-binding protein 1 and altered phosphorylation levels of major components of IGF1 signalling, a key pathway in the regulation of lifespan(5). This study shows the regulation of mammalian lifespan by a sirtuin family member and has important therapeutic implications for age-related diseases.