Preventing the loss of muscle and function in hospitalized older adults

描述（由申请人提供）：三分之一的65岁以上的独立老年人将因急性内科疾病、受伤或手术而住院。不幸的是，这些老年人中有50%的人在住院期间会经历功能衰退，因为他们在床上不活动。出院后，功能缺陷可能会持续数月，在许多情况下永远不会恢复到住院前的水平，从而加剧发病率、医疗费用和死亡。老年人短期卧床休息的典型后果是骨骼肌质量的显著减少，这是加速腿部力量缺陷的基础。我们已经表明，骨骼肌损失的一个重要机制是营养物质无法刺激正常的肌肉蛋白质合成反应；这一过程受到哺乳动物雷帕霉素信号通路靶蛋白（mTOR）和氨基酸转运蛋白的高度调控。产生力量的肌肉组织的日常维持是由肌肉收缩和必需氨基酸摄入的合成代谢刺激决定的。因此，合成代谢干预，如神经肌肉电刺激（NMES）和含有高比例必需氨基酸（乳清蛋白）的高质量蛋白质补充剂，可能是维持住院老年人腿部肌肉质量和力量的一种有希望的方法，并防止反复的短期缺乏身体活动的长期后果。本研究的目的是在老年人中测试NMES和蛋白质补充的组合是否能够在卧床休息期间保持肌肉质量和力量，并维持肌肉营养合成代谢敏感性。我们目前的假设是，在老年人卧床休息的5天内，每天补充NMES和蛋白质将：1)保持下肢肌肉质量和力量；2)维持肌肉营养合成代谢敏感性，通过mTOR信号和氨基酸转运蛋白表达来测量。这项拨款申请的目的是在受控环境中提供初步数据，以确定这些实际的收缩和营养对策在保持住院老年人的瘦质量和力量方面的有效性。我们的长期目标是在临床环境中利用这种住院预防性治疗方法，其中肌肉质量和力量缺陷严重（例如，重症监护患者）。

DESCRIPTION (provided by applicant): One third of independent older adults over the age of 65y will be hospitalized for an acute medical illness, injury, or operative procedure. Unfortunately, 50% of these older adults will experience functional decline during their hospital stay from the amount of time they are physically inactive and in bed. Following discharge, the functional deficits can persist for months and in many instances never return to pre-hospitalization levels thus compounding morbidity, health care costs and dying. A classic consequence of short-term bed rest in older adults is the significant loss in skeletal muscle mass which underlies the accelerated leg strength deficits. We have shown that an important mechanism of skeletal muscle loss is the inability of nutrients to stimulate a normal muscle protein synthesis response; a process highly regulated by the mammalian target of rapamycin signaling pathway (mTOR) and amino acid transporters. Day to day maintenance of force generating muscle tissue is dictated by anabolic stimulation from muscle contraction and essential amino acid ingestion. Therefore, anabolic interventions such as neuromuscular electrical stimulation (NMES) and high quality protein supplementation that contains a high proportion of essential amino acids (whey protein) may be a promising approach to maintain leg muscle mass and strength in hospitalized older adults and prevent the long term consequences of repeated periods of short-term physical inactivity. The purpose of this study is to test in olde adults if the combination of NMES and protein supplementation is capable of preserving muscle mass and strength and maintaining muscle nutrient anabolic sensitivity during bed rest. Our current hypotheses are that daily NMES and protein supplementation during 5-days of bed rest in older adults will: 1) preserve lower extremity muscle mass and strength and 2) maintain muscle nutrient anabolic sensitivity as measured by mTOR signaling and amino acid transporter expression. This grant application is designed to provide preliminary data in a controlled setting to determine the effectiveness of these practical contractile and nutritional countermeasures in maintaining lean mass and strength in hospitalized older adults. Our long-term goal is to utilize this inpatient preventative therapeutic approach in a clinical setting in which muscle mass and strength deficits are profound (e.g., intensive care patients).