Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China.
Pharmacol Ther. 2012 Dec;136(3):305-18. doi: 10.1016/j.pharmthera.2012.08.009. Epub 2012 Aug 24.
Sirtuin 1 (SIRT1), the mammalian ortholog of yeast Sir2p, is a highly conserved NAD(+)-dependent protein deacetylase that has emerged as a key cardiometabolic regulator. During the past decade, Sir2p has been the focus of intense investigations and discussion because it regulates longevity in yeast, worms and flies. Although the extrapolation of data obtained from yeast Sir2p to mammalian SIRT1 cannot be automatic, animal studies provide convincing evidence that SIRT1 is a potent protector against aging-associated pathologies, in particular metabolic disorders and cardiovascular diseases. Indeed, many exciting connections exist between the protein deacetylation function of SIRT1 and its role in fundamental biological responses to various nutritional and environmental signals. As a result, pharmaceutical and nutriceutical interventions targeting SIRT1 are promising strategies to combat aging-associated diseases. The present review summarizes the recent progress in SIRT1 research with a particular focus on the specificities of this protein in individual tissues as they relate to cardiometabolic control.
Sirtuin 1（SIRT1）是酵母 Sir2p 的哺乳动物同源物，是一种高度保守的 NAD（+）依赖性蛋白去乙酰化酶，已成为关键的心脏代谢调节剂。在过去的十年中，Sir2p 一直是激烈研究和讨论的焦点，因为它调节酵母、蠕虫和苍蝇的寿命。虽然不能自动将从酵母 Sir2p 获得的数据推断到哺乳动物 SIRT1 上，但动物研究提供了令人信服的证据，证明 SIRT1 是对抗与衰老相关的病理，特别是代谢紊乱和心血管疾病的有力保护者。事实上，SIRT1 的蛋白去乙酰化功能与其对各种营养和环境信号的基本生物学反应的作用之间存在许多令人兴奋的联系。因此，针对 SIRT1 的药物和营养干预措施是对抗与衰老相关疾病的有前途的策略。本综述总结了 SIRT1 研究的最新进展，特别关注该蛋白在与心脏代谢控制相关的个体组织中的特异性。
