巨自噬在老年小鼠脑组织以及衰老的人类成纤维细胞中受损。
Macroautophagy is impaired in old murine brain tissue as well as in senescent human fibroblasts.
作者信息
Ott Christiane, König Jeannette, Höhn Annika, Jung Tobias, Grune Tilman
机构信息
Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany.
Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany.
出版信息
Redox Biol. 2016 Dec;10:266-273. doi: 10.1016/j.redox.2016.10.015. Epub 2016 Oct 26.
The overall decrease in proteolytic activity in aging can promote and accelerate protein accumulation and metabolic disturbances. To specifically analyze changes in macroautophagy (MA) we quantified different autophagy-related proteins (ATGs) in young, adult and old murine tissue as well as in young and senescent human fibroblasts. Thus, we revealed significantly reduced levels of ATG5-ATG12, LC3-II/LC3-I ratio, Beclin-1 and p62 in old brain tissue and senescent human fibroblasts. To investigate the role of mTOR, the protein itself and its target proteins p70S6 kinase and 4E-BP1 were quantified. Significant increased mTOR protein levels were determined in old tissue and cells. Determination of phosphorylated and basal amount of both proteins suggested higher mTOR activity in old murine tissue and senescent human fibroblasts. Besides the reduced levels of ATGs, mTOR can additionally reduce MA, promoting further acceleration of protein accumulation and metabolic disturbances during aging.
衰老过程中蛋白水解活性的整体下降会促进并加速蛋白质积累和代谢紊乱。为了具体分析巨自噬（MA）的变化，我们对年轻、成年和老年小鼠组织以及年轻和衰老的人类成纤维细胞中的不同自噬相关蛋白（ATG）进行了定量。因此，我们发现老年脑组织和衰老的人类成纤维细胞中ATG5-ATG12、LC3-II/LC3-I比值、Beclin-1和p62的水平显著降低。为了研究mTOR的作用，我们对该蛋白本身及其靶蛋白p70S6激酶和4E-BP1进行了定量。在老年组织和细胞中检测到mTOR蛋白水平显著升高。对这两种蛋白的磷酸化和基础量的测定表明，老年小鼠组织和衰老的人类成纤维细胞中mTOR活性较高。除了ATG水平降低外，mTOR还可进一步减少巨自噬，从而在衰老过程中进一步加速蛋白质积累和代谢紊乱。
Zotero 插件