EXERCISE INTERVENTIONS DURING VOLUNTARY WEIGHT LOSS IN OBESE OLDER ADULTS

描述（由申请人提供）：肥胖通过加剧与年龄相关的身体功能下降，导致肥胖老年人虚弱。然而，老年人肥胖的适当管理是有争议的。不运动的减肥会加速与年龄相关的肌肉和骨量下降，从而导致肌肉减少症和骨质减少症，从而加重身体虚弱。由于肥胖老年人虚弱的重要问题，确定最有效的方法来减少甚至扭转这一人群的虚弱是很重要的。本提案的主要目的是评估哪种不同类型的体育锻炼（阻力、有氧或联合）在预防减肥引起的肌肉和骨量减少和逆转肥胖老年人的虚弱方面最有效。将160名肥胖老年人随机分为1)10%减肥+阻力训练，2)10%减肥+有氧训练，3)10%减肥+有氧/阻力训练，4)非减肥对照组，为期6个月。我们假设：1)减重+阻力训练比减重+有氧训练和减重+有氧/阻力训练对身体机能的改善更大；2)减重+阻力训练比减重+有氧/阻力训练更能保持肌肉量，而减重+有氧训练会导致肌肉量减少。3)与减重+有氧/阻力训练相比，减重+阻力训练更能刺激骨形成，而不是骨吸收，因此，保持骨密度，而减重+有氧训练将减少骨转换，减轻骨密度的损失。4)减肥+阻力训练a)与有氧和有氧/阻力训练相比，将导致骨骼肌中TNF-1和IL-6的更大下降和MGF的更大增加，b)这些合成代谢作用将与减肥治疗期间肌肉蛋白合成（MPS）和肌肉质量的保存相关。我们的总体假设是，肥胖和衰老对身体成分（肌肉减少性肥胖）和身体功能（虚弱）有附加的不利影响，这是由它们对炎症和MPS的附加不利影响介导的，因此，通过减肥+抗阻训练可以显着改善。因此，为了以综合的方式检验这一中心假设，我们将使用偏相关和多元回归分析，以确定哪些身体成分因素和/或机械骨骼肌因素是观察到的身体功能变化的最重要的介质。老年人肥胖是一个主要的公共卫生问题。肥胖老年人的数量在我们的社会将继续增加，挑战现有的医疗保健服务系统。这项建议的随机对照试验的结果将对预防我们社会中肥胖老年人功能独立性的丧失具有重要意义，因此，将改变目前针对这一快速增长的人群的临床实践。公共卫生相关性：老年人肥胖是一个主要的公共卫生问题，对卫生保健专业人员和我们现有的卫生保健提供系统提出了挑战。肥胖加剧了随着年龄增长而出现的身体功能衰退，并增加了在社区中丧失独立性的风险。这项研究将确定预防我们社会中肥胖老年人功能独立性丧失的最有效方法，并将改变目前针对这一快速增长的人群的临床实践。

DESCRIPTION (provided by applicant): Obesity causes frailty in obese older adults by exacerbating the age-related decline in physical function. However, appropriate management of obesity in older adults is controversial. Weight loss without exercise could worsen frailty by accelerating the usual age-related decline in muscle and bone mass that leads to sarcopenia and osteopenia, respectively. Because of the important problem of frailty in obese older adults, it would be important to determine the most efficacious approach in reducing, or even reversing frailty in this population. The primary objective of this proposal is to evaluate which distinct type of physical exercise (resistance, aerobic, or combined) is most efficacious in preventing the weight-loss-induced reduction in muscle and bone mass and reversing frailty in obese older adults. A total of 160 obese older adults will be randomized to 1) 10% weight loss + resistance training, 2) 10% weight loss + aerobic training, 3) 10% weight loss + aerobic/resistance training, and 4) non-weight loss control group for 6 months. We hypothesize that 1) weight loss + resistance training will cause a greater improvement in physical function than weight loss + aerobic training and weight loss + aerobic/resistance training, 2) weight loss + resistance training will cause a greater preservation of muscle mass than weight loss + aerobic/resistance training, whereas weight loss + aerobic training will cause a decrease in muscle mass, 3) weight loss + resistance training will stimulate bone formation more than resorption compared to weight loss + aerobic/resistance training and, thus, preserve BMD, whereas weight loss + aerobic training will decrease bone turnover and attenuate the loss of BMD, and 4) weight loss + resistance training a) will cause a greater decrease in TNF-1 and IL-6 and a greater increase in MGF in skeletal muscles than aerobic and aerobic/resistance training and that b) these anabolic effects will correlate with preservation of muscle protein synthesis (MPS) and muscle mass during weight-loss therapy. Our overarching hypothesis across aims is that obesity and aging have additive adverse effects on body composition (sarcopenic obesity) and physical function (frailty), mediated by their additive adverse effects on inflammation and MPS, which will, thus, be significantly improved by weight loss + resistance training. Therefore, to test this central hypothesis in an integrated manner, we will use partial correlation and multiple regression analyses, to determine which of the body composition factors and/or the mechanistic skeletal muscle factors are the most important mediators for the observed changes in physical function. Obesity in older adults is a major public health problem. The number of obese older adults in our society will continue to increase, challenging existing health care delivery systems. The results of this proposed RCT will have important implications for preventing the loss of functional independence of obese older adults in our society and, therefore, will change current clinical practice for this rapidly growing segment of the population. PUBLIC HEALTH RELEVANCE: Obesity in older adults is a major public health problem that provides a challenge to health care professionals and our existing health care delivery systems. Obesity worsens the decline in physical function that occurs with age, and increases the risk for loss of independence in the community. This study will determine the most efficacious approach towards preventing the loss of functional independence of obese older adults in our society and will change current clinical practice for this rapidly increasing segment of the population.