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首页> 外文期刊>Biochimica et Biophysica Acta. Gene Regulatory Mechanisms >Sirtuin activators: Designing molecules to extend life span
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Sirtuin activators: Designing molecules to extend life span

机译：Sirtuin活化剂：设计分子以延长寿命

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Resveratrol (RESV) exerts important pharmacological effects on human health: in addition to its beneficial effects on type 2 diabetes and cardiovascular diseases, it also modulates neuronal energy homeostasis and shows antiaging properties. Although it clearly has free radical scavenger properties, the mechanisms involved in these beneficial effects are not fully understood. In this regard, one area of major interest concerns the effects of RESV on the activity of sirtuin 1 (SIRT1), an NAD+-dependent histone deacetylase that has been implicated in aging. Indeed, the role of SIRT1 is currently the subject of intense research due to the antiaging properties of RESV, which increases life span in various organisms ranging from yeast to rodents. In addition, when RESV is administered in experimental animal models of neurological disorders, it has similar beneficial effects to caloric restriction. SIRT1 activation could thus constitute a potential strategic target in neurodegenerative diseases and in disorders involving disturbances in glucose homeostasis, as well as in dyslipidaemias or cardiovascular diseases. Therefore, small SIRT1 activators such as SRT501, SRT2104, and SRT2379, which are currently undergoing clinical trials, could be potential drugs for the treatment of type 2 diabetes, obesity, and metabolic syndrome, among other disorders. This review summarises current knowledge about the biological functions of SIRT1 in aging and aging-associated diseases and discusses its potential as a pharmacological target.
机译：白藜芦醇（RESV）对人体健康具有重要的药理作用：除对2型糖尿病和心血管疾病具有有益作用外，它还调节神经元能量稳态并显示出抗衰老特性。尽管它显然具有自由基清除剂的性能，但尚未完全了解这些有益作用所涉及的机理。在这方面，一个主要关注的领域是RESV对Sirtuin 1（SIRT1）的活性的影响，Sirtuin 1（SIRT1）是一种NAD +依赖的组蛋白脱乙酰基酶，与衰老有关。确实，由于RESV具有抗衰老特性，因此SIRT1的作用目前已受到广泛研究，这增加了从酵母到啮齿动物的各种生物的寿命。另外，当在神经系统疾病的实验动物模型中施用RESV时，它与热量限制具有相似的有益作用。因此，SIRT1激活可能构成神经退行性疾病和涉及葡萄糖稳态平衡异常以及血脂异常或心血管疾病的潜在战略目标。因此，目前正在接受临床试验的小型SIRT1激活剂，例如SRT501，SRT2104和SRT2379，可能是治疗2型糖尿病，肥胖症和代谢综合征等疾病的潜在药物。这篇综述总结了有关SIRT1在衰老和衰老相关疾病中生物学功能的最新知识，并讨论了其作为药理学靶标的潜力。

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