Satoh Akiko, Stein Liana, Imai Shin
Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Handb Exp Pharmacol. 2011;206:125-62. doi: 10.1007/978-3-642-21631-2_7.
Ever since the discovery of sirtuins a decade ago, interest in this family of NAD-dependent deacetylases has exploded, generating multiple lines of evidence implicating sirtuins as evolutionarily conserved regulators of lifespan. In mammals, it has been established that sirtuins regulate physiological responses to metabolism and stress, two key factors that affect the process of aging. Further investigation into the intimate connection among sirtuins, metabolism, and aging has implicated the activation of SIRT1 as both preventative and therapeutic measures against multiple age-associated disorders including type 2 diabetes and Alzheimer's disease. SIRT1 activation has clear potential to not only prevent age-associated diseases but also to extend healthspan and perhaps lifespan. Sirtuin activating compounds and NAD intermediates are two promising ways to achieve these elusive goals.
自十年前发现沉默调节蛋白以来，人们对这个依赖烟酰胺腺嘌呤二核苷酸（NAD）的去乙酰化酶家族的兴趣呈爆发式增长，产生了多条证据表明沉默调节蛋白是寿命的进化保守调节因子。在哺乳动物中，已经证实沉默调节蛋白调节对代谢和应激的生理反应，这是影响衰老过程的两个关键因素。对沉默调节蛋白、代谢和衰老之间紧密联系的进一步研究表明，激活SIRT1作为针对包括2型糖尿病和阿尔茨海默病在内的多种与年龄相关疾病的预防和治疗措施。激活SIRT1不仅具有预防与年龄相关疾病的明确潜力，还能延长健康寿命，甚至可能延长寿命。沉默调节蛋白激活化合物和NAD中间体是实现这些难以捉摸目标的两种有前景的方法。
