Foundation Salvatore Maugeri, IRCCS, Scientific Institute of Lumezzane, Brescia 25065, Italy.
Exp Gerontol. 2012 Jan;47(1):23-8. doi: 10.1016/j.exger.2011.10.003. Epub 2011 Oct 12.
Physical exercise is the most effective intervention against sarcopenia of aging; however, the cellular and molecular mechanisms mediating training-induced adaptations are not yet completely understood. Furthermore, it is unclear whether exercise training initiated late in life affects myocyte anabolic signaling in a dose-dependent manner. Hence, we sought to investigate the effects of treadmill exercise and training frequency on anabolic pathways, including insulin signaling, in the skeletal muscle of old rats. Aged (14-16-month-old) male Wistar rats were trained on a treadmill for 3 (EX3) or 5 days/week (EX5) during 8 weeks and compared with age-matched sedentary controls (SED). Four-month-old rats were used as young controls (YC). Protein expression levels of insulin receptor (IR), insulin receptor substrate 1 (IRS-1), activated (phosphorylated) mammalian target of rapamycin (p-mTOR) and glucose transporter GLUT4 were determined in quadriceps muscle extracts via immunoblotting. Mitochondrial cytochrome c oxidase (COX) activity was assessed by histochemical staining, while electron microscopy was employed to quantify the sarcomere volume (V(src)). Body weight (BW) increased, whereas muscle weight (MW) and V(src) decreased with age. EX5, but not EX3 increased MW and V(src), without affecting BW. The expression of IR and GLUT4 was higher in SED rats relative to the YC group. Conversely, protein levels of IRS-1 and p-mTOR as well as COX activity were reduced in advanced age. Compared with SED rats, EX3 animals displayed reduced IR expression and increased IRS-1 levels and COX activity. The expression of GLUT 4 and p-mTOR was unaffected by EX3. EX5 up-regulated IRS-1 and p-mTOR expression and COX activity, while decreasing GLUT4 levels, with no effect on IR expression. In summary, substantial impairments in muscle anabolic pathways, including insulin signaling, were detected in aged sedentary rats. These changes were ameliorated by exercise training, concomitant with improvements in muscle trophism. Benefits were more evident in rats trained for 5 days/week, suggesting that physical exercise initiated late in life affects anabolic signaling in a dose-dependent manner.
身体锻炼是对抗衰老导致的肌肉减少症最有效的干预措施；然而，介导训练引起的适应的细胞和分子机制尚不完全清楚。此外，尚不清楚生命晚期开始的运动训练是否以剂量依赖的方式影响肌细胞合成代谢信号。因此，我们试图研究跑步机运动和训练频率对老年大鼠骨骼肌中合成代谢途径的影响，包括胰岛素信号。将 14-16 月龄的雄性 Wistar 大鼠分为三组：在跑步机上训练 3 天（EX3）或 5 天/周（EX5），持续 8 周，并与年龄匹配的安静对照组（SED）进行比较。将 4 月龄大鼠作为年轻对照组（YC）。通过免疫印迹法测定股四头肌提取物中胰岛素受体（IR）、胰岛素受体底物 1（IRS-1）、磷酸化（磷酸化）哺乳动物雷帕霉素靶蛋白（p-mTOR）和葡萄糖转运蛋白 GLUT4 的蛋白表达水平。通过组织化学染色评估线粒体细胞色素 c 氧化酶（COX）活性，同时通过电子显微镜定量测量肌节体积（V（src））。体重（BW）增加，而肌肉重量（MW）和 V（src）随年龄增长而下降。EX5，但不是 EX3，增加了 MW 和 V（src），而不影响 BW。SED 大鼠的 IR 和 GLUT4 表达高于 YC 组。相反，IRS-1 和 p-mTOR 的蛋白水平以及 COX 活性在高龄时降低。与 SED 大鼠相比，EX3 动物的 IR 表达降低，IRS-1 水平和 COX 活性增加。EX3 对 GLUT 4 和 p-mTOR 的表达没有影响。EX5 上调 IRS-1 和 p-mTOR 的表达和 COX 活性，同时降低 GLUT4 水平，而对 IR 表达没有影响。总之，在久坐不动的老年大鼠中检测到肌肉合成代谢途径的严重损伤，包括胰岛素信号。这些变化通过运动训练得到改善，同时改善了肌肉营养。每周训练 5 天的大鼠受益更为明显，表明生命晚期开始的身体锻炼以剂量依赖的方式影响合成代谢信号。
