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.
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