Sirtuin 家族包含七种 NAD 依赖性酶，其催化蛋白质赖氨酸脱酰化和单 ADP-核糖基化。 Sirtuins 是基因组稳定性和基因表达的中央调节因子，控制关键过程，包括能量代谢、细胞周期、分化、细胞凋亡和衰老。因此，所有去乙酰化酶在细胞稳态和机体健康中都发挥着关键作用，它们的失调与代谢、心血管和神经系统疾病有关。此外，去乙酰化酶在癌症中表现出二分作用，充当背景依赖性肿瘤抑制因子或促进剂。鉴于它们在不同细胞过程中的核心作用，sirtuins 引起了越来越多的研究兴趣，旨在开发激活剂和抑制剂。事实上，sirtuin 调节可能对许多与年龄相关的疾病具有治疗作用，包括糖尿病、心血管和神经退行性疾病以及癌症。此外，异构体选择性调节剂可能会增加我们对沉默调节蛋白生物学的了解，并有助于开发更好的疗法。通过这次综述，我们提供了对沉默调节蛋白药理学的重要见解，并说明了它们的酶活性和生物功能。此外，我们还概述了最相关的去乙酰化酶调节剂的作用模式、结构-活性关系、药理作用和临床应用。© 2024 作者。医学研究评论由 Wiley periodicals LLC 出版。

The sirtuin family comprises seven NAD+-dependent enzymes which catalyze protein lysine deacylation and mono ADP-ribosylation. Sirtuins act as central regulators of genomic stability and gene expression and control key processes, including energetic metabolism, cell cycle, differentiation, apoptosis, and aging. As a result, all sirtuins play critical roles in cellular homeostasis and organism wellness, and their dysregulation has been linked to metabolic, cardiovascular, and neurological diseases. Furthermore, sirtuins have shown dichotomous roles in cancer, acting as context-dependent tumor suppressors or promoters. Given their central role in different cellular processes, sirtuins have attracted increasing research interest aimed at developing both activators and inhibitors. Indeed, sirtuin modulation may have therapeutic effects in many age-related diseases, including diabetes, cardiovascular and neurodegenerative disorders, and cancer. Moreover, isoform selective modulators may increase our knowledge of sirtuin biology and aid to develop better therapies. Through this review, we provide critical insights into sirtuin pharmacology and illustrate their enzymatic activities and biological functions. Furthermore, we outline the most relevant sirtuin modulators in terms of their modes of action, structure-activity relationships, pharmacological effects, and clinical applications.© 2024 The Author(s). Medicinal Research Reviews published by Wiley Periodicals LLC.