二甲雙胍通過增強自噬和改善線粒體功能改善與衰老相關的炎症
作者：
小柯機器人發布時間：2020/5/13 23:50:25
二甲雙胍通過增強自噬並使線粒體功能正常化，從而減輕與衰老相關的炎症，這一成果由美國肯塔基大學Barbara S. Nikolajczyk研究小組經過不懈努力而取得。該研究成果於2020年5月12日在線發表在國際學術期刊《細胞-代謝》上。
細胞因子和生物信息學分析表明，Th17細胞因子的產生將瘦、正常血糖的老年和青年受試者的CD4 + T細胞區分開，並模擬了糖尿病相關Th17的表達譜。與年輕受試者相比，年齡較大的受試者其T細胞在自噬和線粒體生物能學方面存在缺陷，這與氧化還原失衡有關。二甲雙胍通過增加自噬和改善線粒體生物能，改善了Th17炎症反應。
相比之下，靶向自噬的siRNA破壞了年輕受試者T細胞中的氧化還原平衡，並通過激活Th17主要調控因子STAT3激活了Th17表達譜，STAT3進而與IL-17A和F啟動子區結合。靶向線粒體的siRNA則無法激活Th17表達譜。因此研究人員得出以下結論：二甲雙胍在很大程度上改善了自噬和線粒體功能，同時改善了與糖尿病患者炎症相呼應的新發現的炎症特徵。
研究人員表示，年齡是與衰老相關疾病產生炎症不可改變的危險因素。因此，消炎藥有望延長健康期。
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