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疾病、损伤或手术而住院。不幸的是，这些老年人中有50%在住院期间会经历身体功能下降，因为他们不活动和卧床的时间。出院后，功能缺陷可能持续数月，在许多情况下永远不会恢复到住院前的水平，从而增加了发病率、医疗保健费用和死亡。老年人短期卧床休息的一个典型后果是骨骼肌质量的显著损失，这是腿部力量加速不足的基础。我们已经表明，骨骼肌损失的一个重要机制是营养素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靶信号通路（mTOR）和氨基酸转运蛋白的高度调节。肌肉组织产生力量的日常维持取决于肌肉收缩和必需氨基酸摄入的合成代谢刺激。因此，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等合成代谢干预措施可能是维持住院老年人腿部肌肉质量和力量的一种有前途的方法，并防止短期身体活动重复的长期后果。本研究的目的是在老年人中测试NMES和蛋白质补充剂的组合是否能够在卧床休息期间保持肌肉质量和力量并保持肌肉营养合成代谢敏感性。我们目前的假设是，老年人卧床休息5天期间每日补充NMES和蛋白质将：1）保持下肢肌肉质量和力量，2）保持肌肉营养合成代谢敏感性，如通过mTOR信号传导和氨基酸转运蛋白表达所测量的。这项资助申请旨在提供受控环境中的初步数据，以确定这些实用的收缩和营养对策在维持住院老年人瘦体重和力量方面的有效性。我们的长期目标是在肌肉质量和力量严重不足的临床环境中利用这种住院预防性治疗方法（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).