EFFECTS OF DHEA AND EXERCISE ON BONE, MUSCLE AND BALANCE

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。美国国家航空航天局已确定微重力下的骨骼和肌肉损失是成功进行长期太空飞行的关键障碍。此外，约翰·格伦从航天飞机返回后发现的不平衡，以及美国国家航空航天局与巴尔的摩纵向老龄化研究合作评估纵向平衡的举措，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还不完全清楚。在太空旅行中，有几个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、压力反应和蛋白质代谢(1，2，3)。在太空旅行中发生的许多变化也会随着年龄的增长而发生，最终导致一种被描述为虚弱的综合症(4，5，6)。随着年龄的增长，变化包括皮质醇和胰岛素水平的增加，性激素的减少，营养摄入不足，以及导致骨骼、肌肉和平衡丧失的厌食症。研究可以减轻衰老对虚弱的老年人的影响的干预措施，可能会为最大限度地减少空间中骨骼、肌肉和平衡丧失的对策和战略提供见解。大多数老年病医生同意，虚弱是一种储备减少和对应激源的抵抗力下降的综合征，导致多个生理系统的累积下降，从而增加对不利结果的易感性(4，5，6)。身体虚弱的标志包括瘦体重、力量、耐力、平衡、行走能力、低活动量等方面的下降，还有一些包括骨量减少(4，5，6，7)。脆弱性的许多组成部分是相互关联的，而且都与外汇储备的下降有关。由于这些成分中的多个必须在临床上存在才能构成脆弱，因此可以预见到一个从健壮到脆弱再到脆弱的物理连续体。弗里德等人。提出了脆弱的表型，从脆弱的身体标志中突出了5个特征，并使用该表型评估了基线脆弱状况对3年和7年随访的健康结局发生率的贡献(8)。对于这种表型，脆弱被定义为具有5个特征中的3个，而脆弱具有5个特征中的1个或2个。虚弱和早衰与死亡、住院、跌倒、ADL残疾恶化和行动不便的风险增加有关(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。这种作用的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发挥作用。或者，这种影响可能是间接的，抵消了压力反应的影响。假说：通过补充脱氢表雄酮(DHEAS)和哈达瑜伽，选择DHEAS水平低于305 ng/dl的虚弱女性，肌肉力量和平衡能力将得到改善。这两种疗法的效果都将比单独使用任何一种疗法更好地改善结果，而且可能是相加的。此外，经过脱氢表雄酮和/或瑜伽治疗后，瘦体重、骨骼肌质量、骨转换指标和体能都会有所改善。

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.