EFFECT OF RESISTANCE EXERCISE AND REDUCTION OF BLOOD FLOW ON MUSCLE GROWTH IN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 雷帕霉素(MTOR)信号通路在刺激翻译起始和肌肉蛋白质合成中起着重要作用。虽然肌肉收缩和低氧都能显著上调AMPK活性，但低氧本身对肌肉蛋白质代谢的影响尚不清楚。此外，最近的研究表明，缺氧可以通过一种名为缺氧诱导因子-1(HIF1)的转录因子上调mTOR信号通路。低氧诱导的血管生成和心肌细胞生长与HIF1有关；因此，阻力运动结合限制静脉血流可能通过HIF1进一步刺激mTOR信号通路。 其具体目的是：1)确定在老年男性肌肉收缩联合局部缺氧的情况下，mTOR信号通路的哪个组成部分(S)发生了改变。2)确定在低强度运动中限制血流是否比只进行常规阻力运动对老年男性肌肉蛋白质合成的增加更大。我们将研究24名年龄较大(60岁及以上)的男性在隔夜禁食后的情况。该方案旨在研究静息和低强度耐力运动后肌肉混合蛋白合成率(FSR)和mTOR信号通路中参与翻译起始的成分(mTOR、p70S6K、eIF2B、HIFs和AMPK)的总蛋白含量和磷酸化状态的变化。这些研究将为阻力运动结合肌肉血流量减少增强肥大效应的细胞机制提供洞察力。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Rapamycin (mTOR) signaling pathway plays a significant role in stimulating translation initiation and muscle protein synthesis. Though both muscular contraction and hypoxia have been demonstrated to acutely up regulate AMPK activity, effect of hypoxia per se on muscle protein turnover is unknown. Additionally, recent studies have shown that hypoxia can up-regulate the mTOR signaling pathway through a transcription factor called hypoxia-inducible factor-1 (HIF1). Hypoxia induced angiogenesis and cardiac cell growths have been linked to HIF1; therefore, resistance exercise combined with restricted venous blood flow may further stimulate mTOR signaling pathway through HIF1. The specific aims are to: 1) to determine which component(s) of the mTOR signaling pathway are modified with muscular contraction combined with local hypoxia in older men. 2) To determine whether blood flow restriction during low-intensity exercise produces a larger increase in muscle protein synthesis than regular resistance exercise alone in older men. We will study groups of 24 older (60 yrs and above yrs) men after an overnight fast. The protocol is designed to study the modulations in mixed muscle protein fractional synthetic rate (FSR) and total protein content and phosphorylation status of components of the mTOR signaling pathway involved in translation initiation (mTOR, p70S6K, eIF2B, HIFs and AMPK) at rest and after low intensity resistance exercise with or without vascular occlusion. These studies will provide insight into the cellular mechanisms responsible for the enhanced hypertrophic effect of resistance exercise combined with reduced muscular blood flow.