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二甲双胍通过增强自噬并使线粒体功能正常化，从而减轻与衰老相关的炎症，这一成果由美国肯塔基大学Barbara S. Nikolajczyk研究小组经过不懈努力而取得。该研究成果于2020年5月12日在线发表在国际学术期刊《细胞-代谢》上。

细胞因子和生物信息学分析表明，Th17细胞因子的产生将瘦、正常血糖的老年和青年受试者的CD4 ⁺ T细胞区分开，并模拟了糖尿病相关Th17的表达谱。与年轻受试者相比，年龄较大的受试者其T细胞在自噬和线粒体生物能学方面存在缺陷，这与氧化还原失衡有关。二甲双胍通过增加自噬和改善线粒体生物能，改善了Th17炎症反应。

相比之下，靶向自噬的siRNA破坏了年轻受试者T细胞中的氧化还原平衡，并通过激活Th17主要调控因子STAT3激活了Th17表达谱，STAT3进而与IL-17A和F启动子区结合。靶向线粒体的siRNA则无法激活Th17表达谱。因此研究人员得出以下结论：二甲双胍在很大程度上改善了自噬和线粒体功能，同时改善了与糖尿病患者炎症相呼应的新发现的炎症特征。

研究人员表示，年龄是与衰老相关疾病产生炎症不可改变的危险因素。因此，消炎药有望延长健康期。

附：英文原文

Title: Metformin Enhances Autophagy and Normalizes Mitochondrial Function to Alleviate Aging-Associated Inflammation

Author: Leena P. Bharath, Madhur Agrawal, Grace McCambridge, Dequina A. Nicholas, Hatice Hasturk, Jing Liu, Kai Jiang, Rui Liu, Zhenheng Guo, Jude Deeney, Caroline M. Apovian, Jennifer Snyder-Cappione, Gregory S. Hawk, Rebecca M. Fleeman, Riley M.F. Pihl, Katherine Thompson, Anna C. Belkina, Licong Cui, Elizabeth A. Proctor, Philip A. Kern, Barbara S. Nikolajczyk

Issue&Volume: 2020-05-12

Abstract: Age is a non-modifiable risk factor for the inflammation that underlies age-associated diseases; thus, anti-inflammaging drugs hold promise for increasing health span. Cytokine profiling and bioinformatic analyses showed that Th17 cytokine production differentiates CD4+ T cells from lean, normoglycemic older and younger subjects, and mimics a diabetes-associated Th17 profile. T cells from older compared to younger subjects also had defects in autophagy and mitochondrial bioenergetics that associate with redox imbalance. Metformin ameliorated the Th17 inflammaging profile by increasing autophagy and improving mitochondrial bioenergetics. By contrast, autophagy-targeting siRNA disrupted redox balance in T cells from young subjects and activated the Th17 profile by activating the Th17 master regulator, STAT3, which in turn bound IL-17A and F promoters. Mitophagy-targeting siRNA failed to activate the Th17 profile. We conclude that metformin improves autophagy and mitochondrial function largely in parallel to ameliorate a newly defined inflammaging profile that echoes inflammation in diabetes.

DOI: 10.1016/j.cmet.2020.04.015

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30197-2

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