Sirtuins (SIRT1-7), a class of NAD+-dependent deacylases, are central regulators of metabolic homeostasis and stress responses. While numerous salutary effects associated with sirtuin activation, especially SIRT1, are well documented, other reports show health benefits resulting from sirtuin inhibition. Furthermore, conflicting findings have been obtained regarding the pathophysiological role of specific sirtuin isoforms, suggesting that sirtuins act as 'double-edged swords'. Here, we provide an integrated overview of the different findings on the role of mammalian sirtuins in neurodegenerative and cardiometabolic disorders and attempt to dissect the reasons behind these different effects. Finally, we discuss how addressing these obstacles may provide a better understanding of the complex sirtuin biology and improve the likelihood of identifying effective and selective drug targets for a variety of human disorders.

中文翻译：

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二分Sirtuins：在神经退行性疾病和心脏代谢疾病中发现药物的意义。

Sirtuins（SIRT1-7）是一类NAD +依赖性脱酰基酶，是代谢稳态和应激反应的主要调节剂。尽管与沉默调节蛋白激活相关的许多有益作用，尤其是SIRT1，已有大量文献记载，但其他报告显示，沉默调节蛋白的抑制作用可带来健康益处。此外，关于特定瑟土因同工型的病理生理作用，已经获得了相互矛盾的发现，这表明瑟土因起着“双刃剑”的作用。在这里，我们提供了关于哺乳动物沉默调节蛋白在神经退行性疾病和心脏代谢疾病中作用的不同发现的综合概述，并试图剖析这些不同作用背后的原因。最后，