Oh Eunjin, Miller Richard A, Thurmond Debbie C
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Department of Pathology and Geriatrics Center, University of Michigan School of Medicine, Ann Arbor, MI 48109-2200, USA.
Cell Metab. 2015 Sep 1;22(3):499-507. doi: 10.1016/j.cmet.2015.07.023.
Indirect evidence suggests that improved insulin sensitivity may contribute to improved lifespan of mice in which aging has been slowed by mutations, drugs, or dietary means, even in stocks of mice that do not show signs of late-life diabetes. Peripheral responses to insulin can be augmented by overexpression of Syntaxin 4 (Syn4), a plasma-membrane-localized SNARE protein. We show here that Syn4 transgenic (Tg) mice with high level expression of Syn4 had a significant extension of lifespan (33% increase in median) and showed increased peripheral insulin sensitivity, even at ages where controls exhibited age-related insulin resistance. Moreover, skeletal muscle GLUT4 and islet insulin granule exocytosis processes were fully protected in Syn4 Tg mice challenged with a high-fat diet. Hence, high-level expressing Syn4 Tg mice may exert better glycemic control, which slows multiple aspects of aging and extends lifespan, even in non-diabetic mice.
间接证据表明，胰岛素敏感性的提高可能有助于延长因突变、药物或饮食方式而衰老减缓的小鼠的寿命，即使在没有晚期糖尿病迹象的小鼠品系中也是如此。Syntaxin 4（Syn4，一种定位于质膜的SNARE蛋白）的过表达可增强外周对胰岛素的反应。我们在此表明，高表达Syn4的Syn4转基因（Tg）小鼠的寿命显著延长（中位数增加33%），并且外周胰岛素敏感性增加，即使在对照组表现出与年龄相关的胰岛素抵抗的年龄也是如此。此外，在接受高脂饮食挑战的Syn4 Tg小鼠中，骨骼肌GLUT4和胰岛胰岛素颗粒的胞吐过程得到了充分保护。因此，即使在非糖尿病小鼠中，高表达Syn4的Tg小鼠也可能实现更好的血糖控制，从而减缓衰老的多个方面并延长寿命。
