Preserving muscle mass and function in bedridden older adults

保持卧床老年人的肌肉质量和功能

基本信息

批准号：
8606355
负责人：
Douglas Paddon-Jones
金额：
$ 53.13万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-15 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8606355
关键词：
Abbreviations Activities of Daily Living Address Aging Bed rest Beds Body Composition Breath Tests Clinical Clinical Research Clinical Trials Data Monitoring Committees Comorbidity DEXA Defect Deglutition Disorders Desire for food Diet Dietary Intervention Dietary Supplementation Elderly Energy Intake Equilibrium Ergometry Exercise Goals Health Hospitalization Ingestion Injury Inpatients Institutes Insulin Intervention Leg Leucine Measures Medical Metabolic Modeling Morbidity - disease rate Motor Muscle Muscle Proteins Muscle function Nutrient Outcome Patients Physical activity Population Protein Biosynthesis Proteins Recovery Recovery of Function Regulation Rehabilitation therapy Risk Signal Pathway Skeletal Muscle Stimulus Strenuous Exercise Supplementation Testing Texas Theoretical model Translation Initiation Translational Research Universities Weight-Bearing state base bone mass clinical application clinically relevant cost direct application disability experience functional outcomes glucose tolerance human FRAP1 protein insight mTOR protein minimally invasive mortality muscle aging muscle form muscle strength neuromuscular novel older men older women protein degradation protein metabolism response synthetic protein

项目摘要

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.

描述（由申请人提供）：床休息期间老年人的肌肉质量和功能的损失是由于调节肌肉蛋白质代谢的缺陷而促进的，包括对混合营养粉的合成代谢反应的受损能力受损。我们建议，低强度的运动和补充亮氨酸的日常饮食将独立和协同减少不活动对骨骼肌的有害影响，并促进康复过程中的恢复。代谢措施将包括：a）翻译起始的营养和运动特定标记； b）骨骼肌蛋白合成； c）一种新型的葡萄糖耐量测试。形态学和功能措施将包括：a）肌肉质量和身体成分； b）肌肉力量和功能； c）电动机激活。我们将在7天的休息期间测试老年男女（65 - 80年）的以下假设，然后进行7天的住院康复：1。不活动诱导的代谢失调将钝化对餐的代谢反应，从而促进精益肌肉质量的损失，在重新恢复后gl糖质量的能力和功能恢复。 2。补充亮氨酸的每日餐将保持营养刺激的翻译起始，并保留对摄入饮食的代谢反应。这将部分保留卧床休息期间的瘦肌肉和功能，并促进康复过程中功能和代谢能力的恢复。 3。每天的低强度运动将保留运动单位的激活，刺激运动调节的信号通路，并使合成代谢摄入摄入的代谢反应正常化。这将部分保持葡萄糖耐受性，瘦肌肉质量和床休息期间的功能，并促进康复。 4。补充亮氨酸的饮食与低强度运动相比，与单独干预相比，将是一种更有效的刺激，可以保留葡萄糖耐受性，瘦肌肉质量和床休息期间的功能，并促进康复过程中功能和代谢能力的增加。这个翻译项目将为减少身体不活动的负面后果并促进衰老肌肉的康复的策略提供机械和实用的见解。我们的新颖，微创和临床干预措施直接适用于老年住院患者，其肌肉损失和功能能力降低的风险。