Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas, 77550 USA.
Skelet Muscle. 2011 Mar 2;1(1):11. doi: 10.1186/2044-5040-1-11.
Sarcopenia, the loss of skeletal muscle mass during aging, increases the risk for falls and dependency. Resistance exercise (RE) training is an effective treatment to improve muscle mass and strength in older adults, but aging is associated with a smaller amount of training-induced hypertrophy. This may be due in part to an inability to stimulate muscle-protein synthesis (MPS) after an acute bout of RE. We hypothesized that older adults would have impaired mammalian target of rapamycin complex (mTORC)1 signaling and MPS response compared with young adults after acute RE.
We measured intracellular signaling and MPS in 16 older (mean 70 ± 2 years) and 16 younger (27 ± 2 years) subjects. Muscle biopsies were sampled at baseline and at 3, 6 and 24 hr after exercise. Phosphorylation of regulatory signaling proteins and MPS were determined on successive muscle biopsies by immunoblotting and stable isotopic tracer techniques, respectively.
Increased phosphorylation was seen only in the younger group (P< 0.05) for several key signaling proteins after exercise, including mammalian target of rapamycin (mTOR), ribosomal S6 kinase (S6K)1, eukaryotic initiation factor 4E-binding protein (4E-BP)1 and extracellular signal-regulated kinase (ERK)1/2, with no changes seen in the older group (P >0.05). After exercise, MPS increased from baseline only in the younger group (P< 0.05), with MPS being significantly greater than that in the older group (P <0.05).
We conclude that aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. These age-related differences may contribute to the blunted hypertrophic response seen after resistance-exercise training in older adults, and highlight the mTORC1 pathway as a key therapeutic target to prevent sarcopenia.
随着年龄的增长，骨骼肌质量的减少会增加老年人跌倒和依赖的风险。抗阻运动（RE）训练是一种有效改善老年人肌肉质量和力量的方法，但衰老与训练引起的肥大量较小有关。这可能部分是由于急性 RE 后无法刺激肌肉蛋白合成（MPS）。我们假设与年轻人相比，老年人在急性 RE 后，哺乳动物雷帕霉素靶蛋白复合物（mTORC）1 信号和 MPS 反应会受损。
我们测量了 16 名老年人（平均年龄 70 ± 2 岁）和 16 名年轻人（27 ± 2 岁）的细胞内信号和 MPS。在基线和运动后 3、6 和 24 小时分别采集肌肉活检。通过免疫印迹和稳定同位素示踪技术分别在连续的肌肉活检中测定磷酸化调节信号蛋白和 MPS。
仅在年轻人组中，运动后几个关键信号蛋白的磷酸化增加（P<0.05），包括哺乳动物雷帕霉素靶蛋白（mTOR）、核糖体 S6 激酶（S6K）1、真核起始因子 4E 结合蛋白（4E-BP）1 和细胞外信号调节激酶（ERK）1/2，而老年人组没有变化（P>0.05）。运动后，仅在年轻人组中，MPS 从基线增加（P<0.05），且年轻人组的 MPS 显著大于老年人组（P<0.05）。
我们得出结论，衰老会损害收缩引起的人类骨骼肌 mTORC1 信号和蛋白质合成。这些与年龄相关的差异可能导致老年人抗阻训练后出现肥大反应迟钝，并强调 mTORC1 途径是预防肌肉减少症的关键治疗靶点。
