The investigators' general hypothesis is that nutritional factors, including protein/energy malnutrition and/or an impaired response of muscle to nutrition, and inactivity play significant roles in developing sarcopenia, the involuntary loss of muscle mass and function with age. Therefore, age-specific prolonged interventions including nutritional manipulations and/or exercise may help to reduce, stabilize, or even reverse sarcopenia.

Our preliminary studies indicate that, in older adults, muscle protein anabolism is normally stimulated by amino acids alone, but impaired when nutritional stimuli contain carbohydrate due to a relative insulin resistance of muscle protein synthesis. We have also found that amino acids are the most efficient nutrients for the acute stimulation of muscle protein anabolism and our pilot data suggest that they can also increase muscle mass in healthy older adults.

Inactivity is another likely contributor to sarcopenia. Exercise increases not only muscle protein synthesis,mass and strength, but also energy expenditure. Hence, exercise may improve the response of muscle to nutritional interventions in older subjects via increased energy requirements and food consumption, thereby allowing for achievement of true supplementation.

We will test the following specific hypotheses in older, community indwelling, sedentary subjects:

Using a factorial design we will address in older, community-indwelling, sedentary subjects the following hypotheses:

1. Nutritional supplementation with amino acids will improve muscle mass, strength, function, quality, and protein synthesis.
2. Progressive exercise training for 24 weeks will improve muscle mass strength,function, quality, perfusion, and protein metabolism.
3. Combined treatment with nutritional supplementation and progressive exercise training for 24 weeks will improve muscle mass, strength, function, quality, perfusion, and protein metabolism more than either intervention alone.

Our goal is to establish if specific interventions that can acutely increase muscle protein synthesis can also effectively translate into increased muscle mass and/or performance in older sedentary people, thus preventing frailty and promoting physical independence. To this end we will use stable isotope methodologies to measure muscle protein metabolism and contrast enhanced ultrasound to measure muscle perfusion, in order to determine if the treatments' acute effects can predict their chronic impact on muscle mass and function. We will also determine if chronic treatment leads to metabolic and/or vascular adaptations that may explain the measured changes in muscle mass and function.

Inclusion Criteria:

1. age 65-85 yrs
2. ability to sign consent form (score >25 on the 30 item Mini Mental State Examination, MMSE)
3. stable body weight for at least 1 year (verified via medical records).

Exclusion Criteria:

1. physical dependence or frailty (impairment in any of the Activities of Daily Living (ADL), history of falls (≥2/year) or significant weight loss in the past year)
2. exercise training (≥2 weekly sessions of moderate-to-high intensity aerobic or resistance exercise)
3. significant heart, liver, kidney, blood or respiratory disease
4. peripheral vascular disease
5. diabetes or other untreated endocrine disease
6. active cancer
7. recent (within 6 months) treatment with anabolic steroids, or corticosteroids
8. alcohol or drug abuse
9. tobacco use (smoking or chewing, verified via medical records)
10. depression (>5 on the 15-item Geriatric Depression Scale (GDS))
11. malnutrition (BMI <20 kg/m2; hypoalbuminemia or hypotransferrenemia; protein intake<0.66 g/kg/day at run-in)
12. obesity (BMI>30 kg/m2).