DHEA+EXERCISE EFFECT ON SARCOPENIA & OSTEOPENIA OF AGING

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。脱氢表雄酮随着年龄的增长而急剧下降。已发现低脱氢表雄酮水平与肌肉减少症和骨质减少症有关。因此，假定许多衰老的生理变化是继发于脱氢表雄酮的下降。因此，本研究的目的是评估脱氢表雄酮替代对健康老年人身体成分、肌肉功能和代谢以及骨量的年龄相关变化的影响。具体目的是评估10个月的DHEA替代（50 mg/d）结合阻力运动训练对a)全身脂肪含量和瘦体重，腹内脂肪量和大腿肌肉面积，肌肉蛋白质周转和合成的影响；B)全身、腰椎、髋部骨密度及骨转换生化指标；c)胰岛素敏感性。肌肉蛋白的合成速率将由13c -亮氨酸并入骨骼肌蛋白的速率决定。GC/四极杆/质谱和GC/燃烧/质谱将用于定量血浆、肌肉游离氨基酸和肌肉结构蛋白中的13c -亮氨酸丰度。据推测，DHEA会增加肌肉和骨量，减少内脏脂肪量，增加胰岛素敏感性，这些影响将与运动相加或协同作用。65-78岁的健康但久坐不动的受试者将随机接受DHEA， 50毫克/天，持续10个月。所有参与者都将参加为期四个月的有监督的运动训练项目。有监督的锻炼计划将包括阻力训练，旨在增加肌肉质量，力量和骨量，减少脂肪量。本研究的目的是为DHEA替代疗法在维持老年人身体健康和功能能力方面的潜在作用提供信息。

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. DHEA declines dramatically with age. Low DHEA levels have been found to correlate with sarcopenia and osteopenia. It is therefore postulated that many physiologic changes of aging are secondary to the decline in DHEA. Thus the objective of the proposed research is to evaluate the effect of DHEA replacement on age-related changes in body composition, muscle function and metabolism, and bone mass in healthy older adults. The specific aims are to evaluate the effects of 10 months of DHEA replacement (50 mg/d) in combination with resistance exercise training on a) total body fat content and lean body mass, intra-abdominal fat volume and thigh muscle area, and muscle protein turnover and synthesis ; b) bone mineral density of the total body, lumbar spine and hip and biochemical markers of bone turnover; and c) insulin sensitivity. Muscle protein synthesis rate will be determined by the incorporation rate of 13C-leucine into skeletal muscle proteins. GC/quadrupole/MS and GC/combustion/MS will be used to quantify 13C-leucine abundance in plasma, muscle free amino acids, and structural muscle proteins. It is hypothesized that DHEA administration will increase muscle and bone mass, decrease visceral fat mass, and increase insulin sensitivity and that these effects will be additive or synergistic with exercise. Healthy but sedentary subjects, aged 65-78 yr. old will be randomized to receive either DHEA, 50 mg/d for ten months. All participants will participate in supervised exercise training programs for four months. The supervised exercise program will consist of resistance training designed to increase muscle mass, strength, and bone mass, and decrease fat mass. The goal of this research is to provide information on the potential role of DHEA replacement therapy in maintaining the physical health and functional capacity of older people.