Sirtuins belong to an evolutionarily conserved family of NAD⁺-dependent deacetylases that share multiple cellular functions related to proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammalians express seven sirtuins (SIRT1–7) that are localized in different subcellular compartments. Changes in sirtuin expression are critical in several diseases, including metabolic syndrome, diabetes, cancer, and aging. In the kidney, the most widely studied sirtuin is SIRT1, which exerts cytoprotective effects by inhibiting cell apoptosis, inflammation, and fibrosis together with SIRT3, a crucial metabolic sensor that regulates ATP generation and mitochondrial adaptive response to stress. Here, we provide an overview of the biologic effects of sirtuins and the molecular targets thereof regulating renal physiology. This review also details progress made in understanding the effect of sirtuins in the pathophysiology of chronic and acute kidney diseases, highlighting the key role of SIRT1, SIRT3, and now SIRT6 as potential therapeutic targets. In this context, the current pharmacologic approaches to enhancing the activity of SIRT1 and SIRT3 will be discussed.

Sirtuins属于NAD ⁺的进化保守家族依赖的脱乙酰基酶，具有与增殖，DNA修复，线粒体能量稳态和抗氧化活性有关的多种细胞功能。哺乳动物表达七个sirtuins（SIRT1–7），它们位于不同的亚细胞区室。瑟土因表达的变化在多种疾病中至关重要，包括代谢综合征，糖尿病，癌症和衰老。在肾脏中，最广泛研究的Sirtuin是SIRT1，它通过抑制细胞凋亡，炎症和纤维化来发挥细胞保护作用，而SIRT3是调节ATP生成和线粒体对应激的适应性反应的重要代谢传感器。在这里，我们概述了沉默调节蛋白的生物学效应及其调节肾脏生理的分子靶标。这篇综述还详细介绍了在沉默调节蛋白对慢性和急性肾脏疾病的病理生理学影响方面取得的进展，强调了SIRT1，SIRT3和现在的SIRT6作为潜在治疗靶点的关键作用。在这种情况下，将讨论增强SIRT1和SIRT3活性的当前药理学方法。