EFFECTS OF DHEA AND EXERCISE ON BONE, MUSCLE AND BALANCE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。微重力下的骨骼和肌肉损失已被美国宇航局确定为长期太空飞行成功的关键障碍。此外，约翰·格伦（John Glenn）从航天飞机返回后的不平衡发现以及美国宇航局与巴尔的摩纵向老化研究合作评估纵向平衡的倡议，突出了飞行平衡效应的潜在重要性。微重力下的骨骼和肌肉损失尚未完全了解。太空旅行期间发生的几种变化可能会影响骨骼和肌肉的变化，包括失重，激素变化，营养变化，应激反应和蛋白质代谢（1，2，3）。太空旅行中发生的许多变化也会随着衰老而发生，并最终导致一种被描述为虚弱的综合征（4，5，6）。随着年龄的增长，皮质醇和胰岛素水平增加，性激素减少，营养摄入不足和厌食症导致骨骼，肌肉和平衡丧失。对可能减轻衰老对体弱老年人影响的干预措施的研究，可以为最大限度地减少太空中骨骼，肌肉和平衡损失的对策和策略提供见解。 大多数老年病学家认为，虚弱是一种储备减少和对压力源的抵抗力下降的综合征，导致多个生理系统的累积下降，导致对不良后果的脆弱性增加（4，5，6）。虚弱的身体标志包括瘦体重、力量、耐力、平衡、行走能力、低活动量的下降，有些还包括骨质减少（4，5，6，7）。脆弱的许多组成部分是相互关联的，所有这些都与储备下降有关。由于临床上必须存在多个这些组成部分才能构成虚弱，因此可以设想从强健到虚弱前期再到虚弱的物理连续体。Fried等人提出了虚弱的表型，强调了虚弱的物理标志物的5个特征，并使用该表型评估了基线虚弱状态对3年和7年随访期间健康结局发生率的贡献（8）。对于这种表型，虚弱被定义为具有5个特征中的3个，而易虚弱具有5个特征中的1个或2个。虚弱和预虚弱与死亡、住院、福尔斯、ADL残疾恶化和活动性恶化的风险增加相关（8）。 脱氢表雄酮（DHEAS）和瑜伽可以减轻或逆转衰老和虚弱对骨骼，肌肉和平衡丧失的影响。其作用机制可能是通过骨骼、肌肉或大脑中的雄激素或雌激素受体直接起作用。或者这种影响可能是间接的，抵消了压力反应的影响。 假设条件：肌肉力量和平衡将改善妇女的脆弱选择脱氢表雄酮硫酸盐（DHEAS）水平低于305纳克/分升治疗DHEAS补充和哈达瑜伽。这两种治疗的效果将改善结果超过单独治疗，并可能是累加的。此外，瘦体重，骨骼肌质量，骨转换和身体表现的标志物将改善与DHEA和/或瑜伽治疗后。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bone and muscle loss in microgravity have been identified by NASA as key barriers to successful long-term space flight. Further, the potential importance of balance effects of flight were highlighted by the disequilibrium findings in John Glenn following his return from a space shuttle flight and the initiative of NASA to assess longitudinally balance in cooperation with the Baltimore Longitudinal Aging Study. The bone and muscle loss in microgravity are not completely understood. There are several changes that occur during space travel that may influence changes in bone and muscle including weightlessness, hormone changes, nutritional changes, stress response, and protein metabolism (1, 2, 3). Many changes that occur with space travel are also seen with aging and culminate in a syndrome described as frailty (4,5,6). Changes with aging include increases in cortisol and insulin levels, decreases in sex hormones, poor nutritional intake and anorexia contributing to bone, muscle and balance loss. Study of interventions that may mitigate the effects of aging on frail, older individuals, may provide insights into countermeasures and strategies for minimizing bone, muscle and balance loss in space. Most geriatricians agree that frailty is a syndrome of decreased reserve and resistance to stressors, resulting in cumulative declines across multiple physiologic systems, resulting in increased vulnerability to adverse outcomes ( 4,5,6). Physical markers of frailty include declines in lean body mass, strength, endurance, balance, walking performance, low activity and some include osteopenia (4,5,6,7). Many of the components of frailty are interrelated and all are associated with declining reserve. Since multiple of these components must be present clinically to constitute frailty, a physical continuum of robust to prefrail to frail can be envisioned. Fried et al. has proposed a phenotype of frailty, highlighting 5 characteristics from the physical markers of frailty, and used the phenotype to assess the contribution of baseline frailty status to the incidence of health outcomes during 3 and 7 years of follow-up (8). For this phenotype, frailty is defined as having 3 of the 5 characteristics and prefrailty has having 1 or 2 of the 5 characteristics. Frailty and prefrailty are associated with increased risk of death, hospitalization, falls, worsening ADL disability and worsening mobility (8). Dehydroepiandosterone (DHEAS) and yoga may mitigate or reverse the effects of aging and frailty on bone, muscle and balance loss. The mechanism of the effects may be direct - working through androgen or estrogen receptors in bone, muscle or brain. Or the effects may be indirect, countering effects of the stress response. Hypotheses: Muscle strength and balance will improve in women with frailty selected for dehydroepiandosterone sulfate (DHEAS) levels below 305 ng/dl treated with DHEAS supplementation and Hatha yoga. The effects of both treatments will improve outcomes more than either treatment alone and may be additive. In addition, lean body mass, skeletal muscle mass, markers of bone turnover and physical performance will improve following treatment with DHEA and/or yoga.