Department of Developmental Biology, Washington University School of Medicine, Campus Box 8103, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Pharmacol Res. 2010 Jul;62(1):42-7. doi: 10.1016/j.phrs.2010.01.006. Epub 2010 Jan 18.
Aging science has recently drawn much attention, and discussions on the possibility of anti-aging medicine have multiplied. One potential target for the development of anti-aging drugs is the SIR2 (silent information regulator 2) family of NAD-dependent deacetylases/ADP-ribosyltransferases, called "sirtuins." Sirtuins regulate many fundamental biological processes in response to a variety of environmental and nutritional stimuli. In mammals, the mammalian SIR2 ortholog SIRT1 has been most studied, and small molecule SIRT1 activators (STACs), including a plant-derived polyphenolic compound resveratrol, have been developed. On the other hand, sirtuin activity is regulated by NAD biosynthetic pathways, and nicotinamide phosphoribosyltransferase (NAMPT) plays a critical role in the regulation of mammalian sirtuin activity. Recent studies have provided a proof of concept for the idea that nicotinamide mononucleotide (NMN), the NAMPT reaction product, can be used as a nutriceutical to activate SIRT1 activity. Based on these recent findings, the possibility of sirtuin-targeted nutriceutical development will be discussed.
衰老科学最近引起了广泛关注，关于抗衰老医学的可能性的讨论也层出不穷。开发抗衰老药物的一个潜在目标是 NAD 依赖性去乙酰化酶/ADP-核糖基转移酶的 SIR2（沉默信息调节因子 2）家族，称为“sirtuins”。Sirtuins 可响应各种环境和营养刺激来调节许多基本的生物学过程。在哺乳动物中，研究最多的是哺乳动物 SIR2 同源物 SIRT1，并且已经开发了小分子 SIRT1 激活剂（STACs），包括植物来源的多酚化合物白藜芦醇。另一方面，sirtuin 活性受 NAD 生物合成途径调节，烟酰胺磷酸核糖基转移酶（NAMPT）在调节哺乳动物 sirtuin 活性方面起着关键作用。最近的研究为以下观点提供了概念验证，即烟酰胺单核苷酸（NMN），NAMPT 的反应产物，可用作激活 SIRT1 活性的营养保健品。基于这些最新发现，将讨论针对 sirtuins 的营养保健品开发的可能性。
