小分子 SIRT1 激活剂治疗衰老和与年龄相关的疾病。
Small molecule SIRT1 activators for the treatment of aging and age-related diseases.
机构信息
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
出版信息
Trends Pharmacol Sci. 2014 Mar;35(3):146-54. doi: 10.1016/j.tips.2013.12.004. Epub 2014 Jan 16.
Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the potential to delay aging and age-related diseases. Sirtuins comprise a family of NAD⁺-dependent deacylases that are central to the body's response to diet and exercise. New studies indicate that both natural and synthetic sirtuin activating compounds (STACs) work via a common allosteric mechanism to stimulate sirtuin activity, thereby conferring broad health benefits in rodents, primates, and possibly humans. The fact that two-thirds of people in the USA who consume multiple dietary supplements consume resveratrol, a SIRT1 activator, underscores the importance of understanding the biochemical mechanism, physiological effects, and safety of STACs.
最近在小鼠身上的研究已经确定了一些单一分子，这些分子可以延缓多种衰老相关疾病并延长寿命。从理论上讲，这样的分子可以同时预防数十种疾病，从而延长健康寿命。在这篇综述中，我们讨论了 SIRT1 激活剂的最新进展、争议、机遇和挑战，这些分子具有延缓衰老和与年龄相关疾病的潜力。Sirtuins 是一组依赖 NAD⁺的去酰基酶，它们是身体对饮食和运动反应的核心。新的研究表明，天然和合成的 Sirtuin 激活化合物（STACs）通过共同的变构机制发挥作用，刺激 Sirtuin 的活性，从而在啮齿动物、灵长类动物，甚至可能在人类中带来广泛的健康益处。事实上，在美国，三分之二的服用多种膳食补充剂的人都在服用白藜芦醇，这是一种 SIRT1 激活剂，这凸显了了解 STACs 的生化机制、生理效应和安全性的重要性。
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