The investigators will test the following hypotheses:

1. Bedrest will blunt the anabolic response to a mixed nutrient meal, facilitating a loss of muscle mass and functional capacity that is only partially restored during rehabilitation.
2. Enriching daily meals with leucine will promote protein synthesis and maintain the anabolic response to mixed nutrient meal ingestion. This will preserve lean muscle mass and function during bedrest and facilitate the recovery of functional and metabolic capacity during rehabilitation.

Our long-term goal is to identify, prevent and remedy defects in the metabolic pathway that contribute to the loss of muscle mass and function during exposure to microgravity. Demographic data indicate that the average age of shuttle crew members has increased from 40.7 yrs in 1995 to 46.7 yrs in 2007 with an increasing number of astronauts over 50 yrs of age. We contend that the loss of muscle mass and function during spaceflight is facilitated by an age-associated, progressive impairment in the ability to mount an anabolic response to standard mixed nutrient meals. We propose that enriching daily meals with a low-volume leucine supplement will reduce the deleterious effects of microgravity on skeletal muscle and facilitate recovery during rehabilitation.

We will employ our established 14 day bed rest protocol to model the skeletal muscle unloading that occurs during microgravity. We will also examine recovery of muscle mass and functional capacity during a 7 day rehabilitation period. We will study 2 groups: CON (Bedrest/Recovery + Placebo; n=15), LEU (Bedrest/Recovery + Leucine; n=15). We will assess a) markers of translation initiation, b) muscle protein synthesis, c) muscle mass and body composition and d) strength and aerobic capacity.

Inclusion Criteria:

1. Age between 45-60
2. Ability to sign informed consent

Exclusion Criteria:

1. Subjects with cardiac abnormalities considered exclusionary by the study physicians
2. Subjects with uncontrolled metabolic disease
3. A GFR <65 mL/min/1.73m2 or evidence of kidney disease or failure
4. Subjects with vascular disease or risk factors of peripheral atherosclerosis
5. Any history of hypo- or hyper-coagulation disorders. (e.g., Coumadin use or history of DVT or PE)
6. Subjects with chronically elevated systolic pressure >150 or a diastolic blood pressure > 100
7. Subjects with implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
8. Subjects with recently (6 months) treated cancer other than basal cell carcinoma
9. Any subject currently on a weight-loss diet or a body mass index > 30 kg/m2
10. Inability to abstain from smoking for duration of study
11. A history of > 20 pack per year smoking
12. Any subject that is HIV-seropositive or has active hepatitis
13. Recent anabolic or corticosteroids use (within 3 months)
14. Subjects with hemoglobin or hematocrit lower than accepted lab values
15. Agitation/aggression disorder
16. History of stroke with motor disability
17. A recent history (<12 months) of GI bleed
18. Any other condition or event considered exclusionary by the PI and faculty physician

Healthy community-dwelling men and women aged 45-60 y old participated in this randomized, double-blind, placebo controlled study. Volunteers were recreationally active but athletically untrained.