Muscle Perfusion and Protein Metabolism in Elderly

描述(由申请人提供)：我们的一般假设是，与年龄相关的骨骼肌灌注减少会减少对老年肌肉合成代谢的刺激。我们的初步结果表明，在大量摄入氨基酸之后，与年轻人相比，老年人肌肉蛋白质的合成明显延迟。我们假设，随着血液氨基酸浓度的增加，组织液浓度和肌肉蛋白质合成的变化在老年人中发生得更加缓慢。此外，我们认为，老年人的这些迟缓反应至少部分是由于肌肉灌注量的减少。我们进一步假设，在氨基酸存在的情况下，运动诱导的肌肉血流量增加，对年轻和老年骨骼肌诱导放大的合成代谢反应具有交互作用。 这项建议的目的是确定增加肌肉灌注量对老年人肌肉蛋白质合成的影响，无论是通过有氧运动还是通过外周血管扩张(股动脉注入硝普钠，以8微克/分钟的速度)，无论有没有氨基酸。此外，我们打算利用一个新的氨基酸动力学四池模型，该模型允许确定血液、细胞内和间质液体中的氨基酸浓度。此外，我们打算使用一种新的超声造影技术来测量腿部总血流量(即激光多普勒血流计)和骨骼肌微血管灌注量(即毛细血管流量和体积)。肌肉动力学将根据在基础和增加血流条件下持续注入氨基酸的反应，在基础和增加血流条件下的氨基酸摄入反应，以及在补充和不补充氨基酸的情况下45分钟的中等有氧运动(45min，最大摄氧量的40%)的反应进行评估。这些研究的结果将提供证据，证明增加肌肉灌注量、氨基酸补充和有氧运动作为改善老年人骨骼肌蛋白质合成的手段的调节作用。

DESCRIPTION (provided by applicant): Our general hypothesis is that age-related decreases in skeletal muscle perfusion diminish the stimulus for anabolism in elderly muscle. Our preliminary results suggest that following a bolus ingestion of amino acids, elderly muscle protein synthesis is markedly delayed as compared to young. We hypothesize that in response to an increase in blood amino acid concentration, changes in interstitial fluid concentrations and muscle protein synthesis occur more sluggishly in the elderly. Further, we propose that these sluggish responses in elderly occur at least in part because of decreased muscle perfusion. We further hypothesize that exercise-induced increases in muscle blood flow, in the presence of amino acids, has an interactive effect on young and elderly skeletal muscle inducing an amplified anabolic response. The goal of this proposal is to determine the effects of increased muscle perfusion on muscle protein synthesis in elderly, either through aerobic exercise or peripheral vasodilation (femoral arterial infusion of sodium nitroprusside at 8 microg/min) both with and without amino acids. Further, we intend to utilize a novel 4-pool model of amino acid kinetics which allows for the determination of blood, intracellular and interstitial fluid amino acid concentrations. Moreover, we intend to use a novel contrast enhanced ultrasound technique to measure total leg blood flow (i.e. laser Doppler flowmetry) and microvascular perfusion (i.e. capillary flow and volume) in skeletal muscle. Muscle kinetics will be evaluated in response to a continuous infusion of amino acids under basal and increased blood flow conditions, in response to a bolus ingestion of amino acids under basal and increased blood flow conditions, and in response to 45 minutes of moderate aerobic exercise (45 min at 40 percent of VO2max), both with and without amino acid supplementation. Results from these studies will provide evidence as to the regulatory role of increased muscle perfusion, amino acid supplementation and aerobic exercise as means of improving skeletal muscle protein synthesis in the elderly.