Preserving muscle mass and function in bedridden older adults

描述（由申请方提供）：肌肉蛋白质代谢调节缺陷（包括对混合营养餐产生合成代谢反应的能力受损）促进了卧床期间老年人肌肉质量和功能的丧失。我们建议，低强度运动和补充亮氨酸的日常膳食将独立和协同减少不活动对骨骼肌的有害影响，并促进康复期间的恢复。代谢指标包括：a）翻译起始的营养和运动特异性标志物; B）骨骼肌蛋白质合成;和c）葡萄糖耐量的新呼吸试验。形态和功能测量将包括：a）肌肉质量和身体组成; B）肌肉力量和功能;以及c）运动激活。我们将在老年男性和女性（65-80岁）中在7天的卧床休息和7天的住院康复期间测试以下假设：1。失活引起的代谢失调将减弱对膳食的合成代谢反应，促进瘦肌肉质量、葡萄糖耐量和功能能力的损失，这些损失在康复期间部分恢复。2.每日膳食中补充亮氨酸将维持营养素刺激的翻译起始，并保持对膳食摄入的合成代谢反应。这将在卧床休息期间部分保留瘦肌肉质量和功能，并在康复期间促进功能和代谢能力的恢复。3.每日低强度运动将保持运动单位激活，刺激运动调节的信号通路，并使膳食摄入的合成代谢反应正常化。这将在卧床休息期间部分保持葡萄糖耐量、瘦肌肉质量和功能，并促进康复。4.补充亮氨酸的膳食与低强度运动相结合将是比单独干预更有效的刺激，在卧床休息期间保持葡萄糖耐量，瘦肌肉质量和功能，并促进康复期间功能和代谢能力的更大增加。这个翻译项目将提供机械和实际的洞察战略，以减少身体不活动的负面影响，促进衰老肌肉的康复。我们的新型微创临床干预措施可直接应用于面临加速肌肉损失和功能能力下降风险的老年住院患者。

DESCRIPTION (provided by applicant): The loss of muscle mass and function in older adults during bed rest is facilitated by defects in the regulation of muscle protein metabolism, including an impaired ability to mount an anabolic response to a mixed nutrient meal. We propose that low-intensity exercise and supplementing daily meals with leucine will independently and synergistically reduce the deleterious effects of inactivity on skeletal muscle and facilitate recovery during rehabilitation. Metabolic measures will include: a) nutrient and exercise-specific markers of translation initiation; b) skeletal muscle protein synthesis; and c) a novel breath test of glucose tolerance. Morphologic and functional measures will include: a) muscle mass and body composition; b) muscle strength and function; and c) motor activation. We will test the following hypotheses in older men and women (65-80 years) during 7 days of bed rest followed by 7 days of inpatient rehabilitation: 1. Inactivity-induced metabolic dysregulation will blunt the anabolic response to meals, facilitating a loss of lean muscle mass, glucose tolerance and functional capacity that is partially restored during rehabilitation. 2. Supplementing daily meals with leucine will maintain nutrient-stimulated translation initiation and preserve the anabolic response to meal ingestion. This will partially preserve lean muscle mass and function during bed rest and facilitate the recovery of functional and metabolic capacity during rehabilitation. 3. Daily low-intensity exercise will preserve motor unit activation, stimulate the exercise-regulated signaling pathway and normalize the anabolic response to meal ingestion. This will partially preserve glucose tolerance, lean muscle mass and function during bed rest and facilitate rehabilitation. 4. Leucine-supplemented meals combined with low-intensity exercise will be a more effective stimulus than either intervention alone, preserving glucose tolerance, lean muscle mass and function during bed rest and facilitating a greater increase in functional and metabolic capacity during rehabilitation. This translational project will provide mechanistic and practical insight into strategies to reduce the negative consequences of physical inactivity and promote rehabilitation in aging muscle. Our novel, minimally invasive and clinically interventions have direct application for older hospitalized patients at risk of accelerated muscle loss and diminished functional capacity.