Sex-specific Determinants of Early-phase Recovery From Skeletal Muscle Disuse

This project is a 2-phase, randomized clinical trial that includes 7 days of unilateral leg disuse (Phase 1), immediately followed by 1 week of bilateral leg rehabilitation (Phase 2). The investigators will recruit cohorts of healthy middle-aged men and women to address their aims: * Demonstrate the sex-specific effects of skeletal muscle disuse (Phase 1) * Identify key molecular determinates of susceptibility of skeletal muscle atrophy (Phase 1) * Map the early, sex-specific molecular time-course of rehabilitation (Phase 2) * Determine if disused and healthy muscle respond similarly to exercise (Phase 2) Healthy, middle-age men and post-menopausal women (50-65 years) will be recruited from the greater Houston/Galveston area. This under-represented research demographic demonstrate few negative metabolic or phenotypic signs of advanced age, but are at increased risk of being hospitalized and experiencing accelerated loss of lean mass and muscle function that parallels a much older population. The goal of this study is to characterize phenotypic and molecular skeletal muscle changes in middle-aged men and women during critical periods of disuse and rehabilitation and ultimately direct the development of targeted and effective prevention and treatment strategies.

Inclusion Criteria: 1. All races and ethnic backgrounds 2. Men and women, age 50-65 years 3. Generally healthy (see exclusion criteria) 4. Able and willing to provide informed consent 5. Ability to speak and read English 6. Post-menopausal women (no menses within the last 12 months) 7. Body mass index: 18.5-35 kg/m2 or BMI\>35 if thigh adiposity does not impair muscle biopsy Exclusion Criteria: 1. Compromised musculoskeletal function that precludes safe participation or use of crutches 2. Pre-menopausal women 3. Hypogonadal men (testosterone \170, diastolic BP\>95 mmHg) 12. Impaired renal function (creatinine \>1.5 mg/dl) 13. Anemia (hematocrit \30 or excess body fat that compromises muscle biopsy collection 27. Acute infectious disease or chronic infection 28. Alcohol or drug abuse 29. Any other condition or event considered exclusionary by study physician