Nutrition & Exercise to Improve Protein Metabolism & Prevent Sarcopenia in Aging

描述（由申请人提供）：我们的一般假设是营养因素和不活动在肌肉减少症的发展中起重要作用。因此，针对年龄的长期干预，包括营养控制和/或锻炼，可能有助于减少、稳定甚至逆转肌肉质量和力量随年龄增长而丧失。然而，先前的研究试图通过营养补充剂来改善老年人的肌肉质量，但收效甚微，因为老年人倾向于通过减少食物摄入量来补偿营养补充剂所提供的能量。因此，有效的老年人营养补充剂应比同等量的普通食物更能促进合成代谢，以限制热量含量，最大限度地提高合成代谢效率（合成代谢效果/传递的能量）。我们的初步数据表明，必需氨基酸是急性刺激肌肉蛋白质合成代谢最有效的营养素，长期使用也可能改善老年人的肌肉质量。此外，不运动是另一个可能导致肌肉减少症的原因。锻炼不仅能增加肌肉质量和力量，还能增加能量消耗。因此，运动可以通过增加能量需求和食物消耗来改善老年受试者肌肉对营养补充的反应，从而实现真正的补充。虽然抗阻运动是最具合成代谢形式的身体活动，但门诊环境的依从性可能令人失望。有氧运动对老年人更有吸引力，也更容易实施。我们的初步数据表明，有氧运动急剧增加肌肉蛋白质合成，使肌肉灌注正常化，并降低肌肉蛋白质的年龄相关胰岛素抵抗。因此，有氧运动可以改善老年人的肌肉蛋白质代谢、力量、功能甚至质量，特别是在与营养干预相结合的情况下。我们将在久坐不动的老年人中测试以下特定假设：一个高效的营养补充剂将增加，与长期治疗，肌肉质量和力量通过刺激净肌肉蛋白质合成。2. 渐进式有氧训练将通过刺激肌肉蛋白质周转和改善肌肉灌注和肌肉质量来增加肌肉力量和功能。3. 高效的营养补充与进行性有氧训练相结合，通过刺激净肌肉蛋白质合成，改善肌肉灌注和肌肉质量，比单独干预更能增加肌肉质量、力量和功能。我们的目标是确定特定的干预措施是否可以急剧增加肌肉蛋白质的合成，也可以有效地转化为增加肌肉质量和老年人久坐不动的表现。

DESCRIPTION (provided by applicant): Our general hypothesis is that nutritional factors and inactivity play significant roles in the development of sarcopenia. Thus, age-specific prolonged interventions including nutritional manipulations and/or exercise may help to reduce, stabilize, or even reverse the loss of muscle mass and strength with age. However, previous studies attempting to improve muscle mass in older subjects using nutritional supplementation had little success, due to a trend for elders to compensate for the energy delivered by nutritional supplements with reduced food intake. Therefore, effective nutritional supplements for the elderly should be more anabolic than the same amount of ordinary food, to limit the caloric content and maximize the anabolic efficiency (anabolic effect/energy delivered). Our preliminary data indicate that essential amino acids are the most efficient nutrients for the acute stimulation of muscle protein anabolism, and that long term utilization may also improve muscle mass in older subjects. Additionally, inactivity is another likely contributor to sarcopenia. Exercise increases not only muscle mass and strength, but also energy expenditure. Hence, exercise may improve the response of muscle to nutritional supplementation in older subjects via increased energy requirements and food consumption, thereby allowing for the achievement of true supplementation. Although resistance exercise is the most anabolic form of physical activity, compliance in the outpatient setting may be disappointing. Aerobic exercise is more appealing and easier to implement in the older population. Our preliminary data indicate that aerobic exercise acutely increases muscle protein synthesis, normalizes muscle perfusion, and reduces the age-related insulin resistance of muscle proteins. Thus, aerobic exercise may improve muscle protein metabolism, strength, function and even mass in older people, particularly when combined with nutritional interventions. We will test the following specific hypotheses in older sedentary subjects: 1. A highly efficient nutritional supplement will increase, with prolonged treatment, muscle mass and strength by stimulating net muscle protein synthesis. 2. Progressive aerobic training will increase muscle strength and function by stimulating muscle protein turnover and improving muscle perfusion and muscle quality. 3. The highly efficient nutritional supplementation combined with progressive aerobic training will increase muscle mass, strength, and function more than either intervention alone by additively stimulating net muscle protein synthesis, and improving muscle perfusion and muscle quality. Our goal is to establish if specific interventions that can acutely increase muscle protein synthesis can also effectively translate into increased muscle mass and performance in older sedentary people. PUBLIC HEALTH RELEVANCE: Our general goal is to find simple and safe interventions to prevent and treat the loss of muscle mass, strength, and function in older persons. Muscle weakness with aging leads to frailty, disability and loss of independence, increasing the risk of institutionalization and death, and greatly increasing healthcare costs. Based on our preliminary data, we propose that prolonged nutritional supplementation with highly effective, age-specific supplements and/or endurance training will enhance muscle mass, strength and function in older persons by increasing muscle growth and quality.