EFFECTS OF DHEA AND EXERCISE ON BONE, MUSCLE AND BALANCE

DHEA 和运动对骨骼、肌肉和平衡的影响

• 批准号: 7377357
• 负责人: ANNE M KENNY
• 金额: $ 7.52万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377357
• 关键词: EFFECTS; DHEA; EXERCISE; BONE; MUSCLE

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。美国宇航局认为，微重力环境下的骨骼和肌肉流失是长期太空飞行成功的主要障碍。此外，约翰·格伦从航天飞机飞行返回后的不平衡发现以及美国宇航局与巴尔的摩纵向老龄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。在微重力下骨骼和肌肉的损失还没有完全了解。在太空旅行期间发生的一些变化可能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）。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，并最终导致一种称为虚弱的综合症（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，厌食症会导致骨骼、肌肉和平衡丧失。研究可以减轻衰老对身体虚弱的老年人的影响的干预措施，可以为减少骨骼、肌肉和空间平衡损失的对策和策略提供见解。大多数老年病学家认为，虚弱是一种储备能力和对压力源抵抗力下降的综合征，导致多个生理系统的累积衰退，从而增加对不良后果的脆弱性（4,5,6）。身体虚弱的标志包括瘦体质量、力量、耐力、平衡、步行表现、低活动量的下降，一些包括骨质减少（4,5,6,7）。脆弱性的许多组成部分是相互关联的，都与储备下降有关。由于这些成分中的多种必须在临床上出现才能构成虚弱，因此可以设想一个从强壮到虚弱到虚弱的物理连续体。Fried等人提出了一种虚弱的表型，强调了虚弱的物理标记的5个特征，并使用表型来评估基线虚弱状态对3年和7年随访期间健康结果发生率的贡献(8)。对于这种表型，易感性被定义为具有5个特征中的3个，易感性具有5个特征中的1个或2个。虚弱和脆弱与死亡、住院、跌倒、ADL残疾恶化和活动能力恶化的风险增加有关(8)。脱氢表雄酮（DHEAS）和瑜伽可以减轻或逆转衰老和脆弱对骨骼、肌肉和平衡丧失的影响。作用的机制可能是直接的——通过骨骼、肌肉或大脑中的雄激素或雌激素受体起作用。或者影响可能是间接的，抵消压力反应的影响。假设：选择硫酸脱氢表雄酮（DHEAS）水平低于305纳克/分升、补充DHEAS和哈达瑜伽治疗的虚弱女性，肌肉力量和平衡将得到改善。两种治疗的效果比单独治疗更能改善结果，并且可能是累加性的。此外，瘦肉质量、骨骼肌质量、骨转换指标和体能表现在接受脱氢表雄酮和/或瑜伽治疗后都会得到改善。