Chang Hung-Chun, Guarente Leonard
Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Glenn Laboratory for the Science of Aging, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Trends Endocrinol Metab. 2014 Mar;25(3):138-45. doi: 10.1016/j.tem.2013.12.001. Epub 2013 Dec 30.
Sirtuins such as SIRT1 are conserved protein NAD(+)-dependent deacylases and thus their function is intrinsically linked to cellular metabolism. Over the past two decades, accumulating evidence has indicated that sirtuins are not only important energy status sensors but also protect cells against metabolic stresses. Sirtuins regulate the aging process and are themselves regulated by diet and environmental stress. The versatile functions of sirtuins including, more specifically, SIRT1 are supported by their diverse cellular location allowing cells to sense changes in energy levels in the nucleus, cytoplasm, and mitochondrion. SIRT1 plays a critical role in metabolic health by deacetylating many target proteins in numerous tissues, including liver, muscle, adipose tissue, heart, and endothelium. This sirtuin also exerts important systemic effects via the hypothalamus. This review will cover these topics and suggest that strategies to maintain sirtuin activity may be on the horizon to forestall diseases of aging.
诸如SIRT1之类的沉默调节蛋白是保守的依赖烟酰胺腺嘌呤二核苷酸（NAD⁺）的去酰基酶，因此它们的功能与细胞代谢有着内在联系。在过去二十年中，越来越多的证据表明，沉默调节蛋白不仅是重要的能量状态传感器，还能保护细胞免受代谢应激。沉默调节蛋白调节衰老过程，其自身也受饮食和环境应激的调控。包括SIRT1在内的沉默调节蛋白的多种功能，得益于它们在细胞内的不同定位，使细胞能够感知细胞核、细胞质和线粒体中能量水平的变化。SIRT1通过使包括肝脏、肌肉、脂肪组织、心脏和内皮在内的许多组织中的多种靶蛋白去乙酰化，在代谢健康中发挥关键作用。这种沉默调节蛋白还通过下丘脑发挥重要的全身效应。本综述将涵盖这些主题，并表明维持沉默调节蛋白活性的策略可能即将出现，以预防衰老相关疾病。
