Department of Biochemistry, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore 117597.
Transl Res. 2011 May;157(5):276-84. doi: 10.1016/j.trsl.2010.11.006. Epub 2010 Dec 28.
Silent information regulator 2 (Sir2/Sirt1), a member of the sirtuin family of class III histone deacetylases, has been implicated extensively in lifespan extension and is a prominent drug target in antiaging medicine. The mammalian Sirt1 has multiple targets, which include histones, transcription factors, and other molecules that collectively modulate energy metabolism, stress response, and cell/tissue survival. Several of Sirt1's substrates regulate key metabolic processes, and Sirt1 activation may underlie the lifespan prolonging effect of caloric restriction. Recent studies have also identified multifaceted protective roles for Sirt1 against cellular senescence and stress in the neural, cardiovascular, and renal systems. Sirt1's activity in multiple tissues may decline with aging, and sustaining or reactivating this activity seems invariably beneficial. Several studies also point towards a general tumor suppressive role for Sirt1, at least in the context of certain human cancers. Development of Sirt1-based therapeutic interventions against systemic aging and aging-associated diseases will benefit from a thorough understanding of underlying pathological mechanisms of diseases as well as metabolic connections between different tissues and organs.
沉默信息调节因子 2（Sir2/Sirt1）是 III 类组蛋白去乙酰化酶中的一员，广泛涉及寿命延长，是抗衰老医学中的一个重要药物靶点。哺乳动物 Sirt1 有多个靶点，包括组蛋白、转录因子和其他分子，它们共同调节能量代谢、应激反应和细胞/组织存活。Sirt1 的几个底物调节关键代谢过程，Sirt1 的激活可能是热量限制延长寿命的基础。最近的研究还发现，Sirt1 在神经、心血管和肾脏系统中具有对抗细胞衰老和应激的多方面保护作用。随着年龄的增长，Sirt1 在多种组织中的活性可能会下降，维持或重新激活这种活性似乎总是有益的。一些研究还指出 Sirt1 具有普遍的肿瘤抑制作用，至少在某些人类癌症的背景下是这样。为了开发针对全身衰老和衰老相关疾病的 Sirt1 治疗干预措施，需要深入了解疾病的潜在病理机制以及不同组织和器官之间的代谢联系。
