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. The loss of muscle strength with aging is a serious medical problem that decreases independence, enhances the probaility of falls, and diminshes the quality of life in older Americans. While resistance exercise programs increase muscle strength in older Americans, compliance and continuation of such routines is many times difficult. Testosterone administration to older men (which creates testosterone concentrations similar to younger men) enhances muscle strength in the lower extremities by increasing muscle protein synthesis. Enhanced absorption of essential amino acids in older subjects will also increase muscle protein synthesis. This proposal will test the hypothesis that androgen therapy combined with nutritional supplementation in older subjects will increase muscle protein synthesis, muscle strength, and stimulate intramuscular regulators of muscle function such as IGF-I and androgen receptor. Because they act through different mechanisms, the combination of the two will cause an additive increase over either treatment alone in the above stated parameters of muscle function. Healthy men and women older than 60 years will be randomized into one of 4 groups: placebo; nutritional supplementation; oxandrolone (0.1 mg/kg); or nutritional supplementation and oxandrolone. Subjects will be studied at baseline and after treatment for 3 months. Oxandrolone is an oral androgen that has been shown to have anabolic effects and a good safety profile in both men and women at doses indicated above. Additional mechanistic information regarding the pathways that regulate muscle protein synthesis will lead to additional therapies that increase muscle strength in older Americans.
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