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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 雷帕霉素（Rapamycin，mTOR）信号通路在刺激翻译起始和肌肉蛋白质合成中起重要作用。 虽然肌肉收缩和缺氧都能急性上调AMPK活性，但缺氧本身对肌肉蛋白质周转的影响尚不清楚。 此外，最近的研究表明，缺氧可以通过称为缺氧诱导因子-1（HIF 1）的转录因子上调mTOR信号通路。 低氧诱导的血管生成和心脏细胞生长与HIF 1有关;因此，阻力运动结合限制静脉血流量可能进一步刺激mTOR信号通路通过HIF 1。 具体目标是：1）确定mTOR信号通路的哪些组分在老年男性中被肌肉收缩结合局部缺氧修饰。 2)确定在老年男性中，低强度运动期间的血流限制是否比单独进行常规阻力运动更能增加肌肉蛋白质合成。我们将研究24名老年（60岁及以上）男性在禁食过夜后的组。 该方案旨在研究静息时和低强度阻力运动（有或无血管闭塞）后混合肌肉蛋白质合成率（FSR）和总蛋白含量的调节以及参与翻译起始的mTOR信号通路组分（mTOR、p70 S6 K、eIF 2B、HIFs和AMPK）的磷酸化状态。 这些研究将提供深入的细胞机制，负责增强肥大作用的阻力运动结合减少肌肉血流量。

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.