长寿蛋白SIRT6在衰老和代谢中作用的研究进展  

Research progress in the role of SIRT6 in aging and metabolism

作　　者：刘永慧 唐莉[1] 梁泰刚[1] 张健[2] 冯丽 LIU Yonghui;TANG Li;LIANG Taigang;ZHANG Jian;FENG Li(School of Pharmacy,Shanxi Medical University,Taiyuan 030001,China;Medicinal Chemistry and Bioinformatics Center,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China)

机构地区：[1]山西医科大学药学院,太原030001 [2]上海交通大学医学院药物化学与生物信息中心,上海200025

出　　处：《上海交通大学学报（医学版）》2024年第11期1439-1446,共8页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家重点研发计划(2023YFF1205103)。

摘　　要：SIRT6是组蛋白去乙酰化酶第三家族长寿蛋白中的一员,具备依赖于烟酰胺腺嘌呤二核苷酸的脱酰基酶活性和单ADP核糖基转移酶活性。SIRT6主要位于细胞核内,可通过核心调控基因组稳定性和相关基因表达,参与控制机体能量代谢和衰老在内的关键过程。鉴于其在维持细胞稳态和机体健康中的关键作用,SIRT6作为潜在的药物靶点引起人们对其靶向调节剂开发广泛的研究兴趣。药物激动长寿蛋白的活性可能治疗与年龄相关的疾病,如衰老、代谢综合征、炎症和生殖健康等。该文综述了SIRT6的结构特征、酶活性、生物学功能,以及SIRT6激动剂的作用机制、药理活性和临床应用。SIRT6,a member of the sirtuin family of histone deacetylases,belongs to the classⅢlongevity proteins and exhibits NAD+-dependent deacetylase and mono-ADP-ribosyltransferase activities.SIRT6 is primarily located in the cell nucleus and plays a pivotal role in regulating genomic stability and relative gene expression,participating in the control of key processes such as energy metabolism and aging.Given its crucial role in maintaining cellular homeostasis and organismal health,SIRT6 has emerged as a potential therapeutic target,sparking significant research interest in the development of targeted modulators.Activating the longevity protein with drugs may provide therapeutic strategies for age-associated diseases,including aging,metabolic syndrome,inflammation,and reproductive health issues.The review elaborates the structural characteristics,enzymatic activities,and biological functions of SIRT6,as well as the mechanisms of action,pharmacological activities,and clinical applications of various SIRT6 activators.

关 键 词：SIRT6 去乙酰化酶活 衰老 代谢 炎症 药物发现 

分 类 号：R966[医药卫生—药理学]