Muscle Perfusion and Protein Metabolism in Elderly

描述（由申请人提供）：我们的一般假设是，骨骼肌灌注的年龄相关性减少减少了老年肌肉的刺激。我们的初步研究结果表明，在大剂量摄入氨基酸后，老年人肌肉蛋白质合成明显延迟。我们推测，在响应于血液中氨基酸浓度的增加，在间质液浓度和肌肉蛋白质合成的变化发生在老年人更缓慢。此外，我们提出，这些缓慢的反应在老年人发生至少部分是因为减少肌肉灌注。我们进一步假设，运动诱导的肌肉血流量增加，在氨基酸的存在下，对年轻和老年骨骼肌诱导放大的合成代谢反应有相互作用。 本提案的目的是确定增加肌肉灌注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外周血管扩张（股动脉输注硝普钠8微克/分钟），无论是否含有氨基酸。此外，我们打算利用一种新的4池模型的氨基酸动力学，允许测定血液，细胞内和间质液的氨基酸浓度。此外，我们打算使用一种新的对比增强超声技术来测量腿部总血流量（即激光多普勒血流仪）和骨骼肌中的微血管灌注（即毛细血管流量和体积）。将在基础和增加血流量条件下对连续输注氨基酸的反应、在基础和增加血流量条件下对大剂量摄入氨基酸的反应以及在补充和不补充氨基酸的情况下对45分钟中度有氧运动（45分钟，VO2max的40%）的反应中评价肌肉动力学。这些研究的结果将为增加肌肉灌注、补充氨基酸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提供证据。

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.