Introduction: Sirtuins in Aging and Diseases
Introduction: Sirtuins in Aging and Diseases
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DOI：
10.1007/978-1-62703-637-5_1
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发表时间：
2013-01-01
期刊：
影响因子：
--
通讯作者：
Guarente, Leonard
中科院分区：
文献类型：
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作者：
Guarente, Leonard
在过去的15年里，发表在sirtuins上的论文数量呈爆炸式增长。Sirtuins和衰老之间的最初联系来自对酵母的研究，研究表明，酵母母细胞的寿命(复制衰老)与Sir2基因的剂量成正比。随后的研究表明，Sir2同系物还可以延缓线虫、果蝇和小鼠的衰老。对sirtuins功能的一个重要见解来自于酵母Sir2p和哺乳动物SIRT1是依赖NAD(+)的蛋白去乙酰基酶的发现。在哺乳动物中，有七个sirtuin(SIRT1-7)。它们的功能似乎不是多余的，部分原因是三个主要是核的(SIRT1、6和7)，三个是线粒体(SIRT3、4和5)，一个是细胞质(SIRT2)。过去十年提供了大量数据，显示许多关键转录因子的脱乙酰基。在这一章中，我将讨论sirtuins在生理学上调节CR效应的证据，然后转向sirtuins与衰老和寿命之间关系的证据。最后，我将讨论sirtuins在衰老疾病中的作用，以及将这些发现转化为治疗重大疾病的新治疗策略的前景。
Over the past 15 years, the number of papers published on sirtuins has exploded. The initial link between sirtuins and aging comes from studies in yeast, in which it was shown that the life span of yeast mother cells (replicative aging) was proportional to the SIR2 gene dosage. Subsequent studies have shown that SIR2 homologs also slow aging in C. elegans, Drosophila, and mice. An important insight into the function of sirtuins came from the finding that yeast Sir2p and mammalian SIRT1 are NAD(+)-dependent protein deacetylases. In mammals, there are seven sirtuins (SIRT1-7). Their functions do not appear to be redundant, in part because three are primarily nuclear (SIRT1, 6, and 7), three are mitochondrial (SIRT3, 4, and 5), and one is cytoplasmic (SIRT2). The past decade has provided an avalanche of data showing deacetylation of many key transcription factors. In this chapter, I will address the evidence that sirtuins mediate the effects of CR on physiology and will then turn to the evidence of a relationship between sirtuins and aging and life span. Finally, I will discuss the roles of sirtuins in diseases of aging and the prospects of translating these findings to novel therapeutic strategies to treat major diseases.