Translational Control of Anabolic Resistance in Aging Muscle

Pre-testing- The baseline evaluation will assess muscle function and strength, and an oral glucose tolerance test. After the baseline visit, participants will be provided with a step activity monitor to track their level of activity. This will provide a baseline of the participant's normal level of physical activity so an accurate level of 75% activity reduction can be determined. A 3-day daily dietary diary will be provided for the participant to self-report prior to the experiment, as well.

Day 1- After the participant completes their normal activity log and dietary diary, they will be asked to return to the research center for a body composition scan and a metabolic study.

The metabolic study will involve blood sampling from an arm vein and muscle biopsies from the thigh before and after a leucine drink.

2-week period of inactivity- After the metabolic study, the participant will return home and maintain a reduced level of activity (75% reduction) for a two-week period. During this time, the participant will receive phone calls from research personnel in order to maintain adherence to the intervention.

Day 14- After the 2-week reduced activity period, the participant will return to the research center to receive a body composition scan and undergo a metabolic study identical to 'Day 1'.

Post-testing- After Day 14, the participant will be asked to return once again to the research center for a oral glucose tolerance test and the exercise lab for muscle function testing.

Inclusion criteria

• Age between 60-85 years
• Ability to sign informed consent
• Free-living, prior to admission

Exclusion criteria

• Cardiac abnormalities considered exclusionary by the study physician (e.g., Chronic heart Failure, right-to-left shunt)
• Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
• History of kidney disease or failure
• Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes, hypercholesterolemia > 250 mg/dl, claudication or evidence of venous or arterial insufficiency upon palpitation of femoral, popliteal and pedal arteries)
• Risk of blood clotting including family history of thrombophilia, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocystinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombine III
• Use of anticoagulant therapy (e.g., Coumadin, heparin)
• Elevated systolic pressure >150 or a diastolic blood pressure > 100
• Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
• Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
• Currently on a weight-loss diet or body mass index > 30 kg/m2
• Chronic systemic corticosteroid use (≥ 2 weeks) within 4 weeks of enrollment and for study duration (intra-articular/topical/inhaled therapeutic or physiologic doses of corticosteroids are permitted). Androgens or growth hormone within 6 months of enrollment and for study duration (topical physiologic androgen replacement is permitted)
• History of stroke with motor disability
• A recent history (<12 months) of GI bleed
• History of liver disease
• History of respiratory disease (acute upper respiratory infection, history of chronic lung disease)
• Prior history of Heparin-Induced Thrombocytopenia
• An HbA1c value at or greater than 6.5%
• Any other condition or event considered exclusionary by the PI and faculty physician