This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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