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，包括营养操作和/或锻炼在内的针对年龄的长期干预可能有助于减少、稳定甚至逆转肌肉质量和力量随年龄的损失。然而，以前试图使用营养补充剂改善老年受试者肌肉质量的研究几乎没有成功，因为老年人倾向于通过减少食物摄入来补偿营养补充剂提供的能量。因此，老年人有效的营养补充剂应该比相同数量的普通食物更具合成代谢，以限制热量含量并最大限度地提高合成代谢效率（合成代谢效果/能量传递）。我们的初步数据表明，必需氨基酸是最有效的营养素的急性刺激肌肉蛋白质的抗氧化剂，长期利用也可以提高肌肉质量在老年人。此外，不活动是肌肉减少症的另一个可能因素。运动不仅增加肌肉质量和力量，还增加能量消耗。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。虽然抗阻运动是身体活动中最具合成代谢作用的形式，但门诊患者的依从性可能令人失望。有氧运动在老年人群中更有吸引力，更容易实施。我们的初步数据表明，有氧运动急性增加肌肉蛋白质的合成，正常化肌肉灌注，并减少与年龄相关的肌肉蛋白的胰岛素抵抗。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，特别是当与营养干预相结合时。我们将在老年久坐不动的受试者中测试以下特定假设：1。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的合成。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.高效的营养补充与渐进式有氧训练相结合，通过增加净肌肉蛋白质合成，改善肌肉灌注和肌肉质量，比单独的干预措施更能增加肌肉质量，力量和功能。我们的目标是确定可以急剧增加肌肉蛋白质合成的特定干预措施是否也可以有效地转化为老年久坐人群的肌肉质量和性能增加。 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，以预防和治疗老年人肌肉质量，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，增加机构化和死亡的风险，并大大增加医疗保健成本。根据我们的初步数据，我们提出，长期营养补充与高效，年龄特定的补充剂和/或耐力训练将提高肌肉质量，力量和功能，在老年人通过增加肌肉生长和质量。

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.