SIRT1 在炎症和衰老中的转译和治疗方面的观点。
Perspectives on translational and therapeutic aspects of SIRT1 in inflammaging and senescence.
机构信息
Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, Rochester, NY 14642, USA.
出版信息
Biochem Pharmacol. 2012 Nov 15;84(10):1332-9. doi: 10.1016/j.bcp.2012.06.031. Epub 2012 Jul 14.
Sirtuin1 (SIRT1), a type III protein deacetylase, is considered as a novel anti-aging protein involved in regulation of cellular senescence/aging and inflammation. SIRT1 level and activity are decreased during lung inflammaging caused by oxidative stress. The mechanism of SIRT1-mediated protection against inflammaging is associated with the regulation of inflammation, premature senescence, telomere attrition, senescence associated secretory phenotype, and DNA damage response. A variety of dietary polyphenols and pharmacological activators are shown to regulate SIRT1 so as to intervene the progression of type 2 diabetes, cancer, cardiovascular diseases, and chronic obstructive pulmonary disease associated with inflammaging. However, recent studies have shown the non-specific regulation of SIRT1 by the aforementioned pharmacological activators and polyphenols. In this perspective, we have briefly discussed the role of SIRT1 in regulation of cellular senescence and its associated secretory phenotype, DNA damage response, particularly in lung inflammaging and during the development of chronic obstructive pulmonary diseases. We have also discussed the potential directions for future translational therapeutic avenues for SIRT1 in modulating lung inflammaging associated with senescence in chronic lung diseases associated with increased oxidative stress.
Sirtuin1(SIRT1)是一种 III 型蛋白去乙酰化酶,被认为是一种新型的抗衰老蛋白,参与细胞衰老/老化和炎症的调节。在氧化应激引起的肺部炎症老化过程中,SIRT1 水平和活性降低。SIRT1 介导的抗炎作用的机制与炎症、过早衰老、端粒磨损、衰老相关分泌表型和 DNA 损伤反应的调节有关。多种膳食多酚和药理激活剂被证明可以调节 SIRT1,从而干预与炎症老化相关的 2 型糖尿病、癌症、心血管疾病和慢性阻塞性肺疾病的进展。然而,最近的研究表明,上述药理激活剂和多酚对 SIRT1 的非特异性调节。在这篇观点文章中,我们简要讨论了 SIRT1 在调节细胞衰老及其相关分泌表型、DNA 损伤反应中的作用,特别是在肺部炎症老化和慢性阻塞性肺疾病发展过程中的作用。我们还讨论了未来针对 SIRT1 的转化治疗途径的潜在方向,以调节与慢性肺部疾病相关的衰老相关的肺部炎症老化,这些疾病与氧化应激增加有关。
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