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缺乏运动在骨质疏松症的发展中起着重要作用。因此，针对年龄的长期干预措施，包括营养操作和/或锻炼，可能有助于减少、稳定、甚至逆转随年龄增长的肌肉质量和力量的丧失。然而，之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，因为老年人有一种趋势，即通过减少食物摄入量来补偿营养补充剂提供的能量。因此，有效的老年人营养补充剂应该比等量的普通食物更具合成代谢作用，以限制卡路里含量，并最大限度地提高合成代谢效率(合成代谢效果/提供的能量)。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的最有效的营养物质，长期服用也可能改善老年受试者的肌肉质量。此外，缺乏运动是另一个可能导致石棺减少的因素。锻炼不仅会增加肌肉质量和力量，还会增加能量消耗。因此，运动可以通过增加能量需求和食物消耗来改善老年人肌肉对营养补充的反应，从而实现真正的补充。虽然阻力运动是最具合成代谢作用的体力活动形式，但门诊环境中的依从性可能会令人失望。有氧运动在老年人中更具吸引力，也更容易实施。我们的初步数据表明，有氧运动可以显著增加肌肉蛋白质的合成，使肌肉血流正常，并降低肌肉蛋白质的与年龄相关的胰岛素抵抗。因此，有氧运动可能会改善老年人的肌肉蛋白质代谢、力量、功能甚至质量，特别是当与营养干预相结合时。我们将在老年久坐受试者中检验以下具体假设：1.随着治疗时间的延长，一种高效的营养补充剂将通过刺激肌肉蛋白质的净合成来增加肌肉质量和力量。2.渐进式有氧训练通过刺激肌肉蛋白质的循环，改善肌肉的灌注量和肌肉质量，增加肌肉的力量和功能。3.高效营养补充与渐进式有氧训练相结合，通过增加肌肉蛋白质的净合成，改善肌肉灌注量和肌肉质量，比单独进行干预更能增加肌肉质量、力量和功能。我们的目标是确定能够显著增加肌肉蛋白质合成的特定干预措施是否也能有效地转化为久坐的老年人的肌肉质量和表现。 公共卫生相关性：我们的总体目标是找到简单而安全的干预措施来预防和治疗老年人的肌肉质量、力量和功能的丧失。随着年龄的增长，肌肉无力会导致虚弱、残疾和丧失独立性，增加住院和死亡的风险，并极大地增加医疗费用。根据我们的初步数据，我们建议长期营养补充，配合高效、特定年龄的补充剂和/或耐力训练，将通过促进肌肉生长和质量来增强老年人的肌肉质量、力量和功能。

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.