Pulmonary and Critical Care medicine, Department of Medicine, Baylor College of Medicine, Houston TX 77030, USA.
Mech Ageing Dev. 2020 Jun;188:111249. doi: 10.1016/j.mad.2020.111249. Epub 2020 Apr 19.
Ageing and obesity have common hallmarks: altered glucose and lipid metabolism, chronic inflammation and oxidative stress are some examples. The downstream effects of SIRT1 activity have been thoroughly explored, and their research is still in expanse. SIRT1 activation has been shown to regulate pathways with beneficiary effects on 1) ageing and obesity-associated metabolic disorders such as metabolic syndrome, insulin resistance and type-II diabetes with, 2) chronic inflammatory processes such as arthritis, atherosclerosis and emphysema, 3) DNA damage and oxidative stress with impact on neurodegenerative diseases, cardiovascular health and some cancers. This knowledge intensified the interest in uncovering the mechanisms regulating the expression and activity of SIRT1. This review focuses on the upstream regulatory mechanisms controlling SIRT1, and how this knowledge could potentially contribute to the development of therapeutic interventions.
葡萄糖和脂质代谢改变、慢性炎症和氧化应激等。SIRT1 活性的下游效应已经得到了深入的研究，其研究仍在不断扩展。SIRT1 的激活已被证明可以调节一些通路，这些通路对以下方面具有有益的影响：1）与衰老和肥胖相关的代谢紊乱，如代谢综合征、胰岛素抵抗和 2 型糖尿病；2）慢性炎症过程，如关节炎、动脉粥样硬化和肺气肿；3）DNA 损伤和氧化应激，对神经退行性疾病、心血管健康和某些癌症有影响。这些知识激发了人们对揭示调节 SIRT1 表达和活性的机制的兴趣。本综述重点介绍了控制 SIRT1 的上游调节机制，以及这些知识如何为治疗干预的发展做出贡献。
