Translational Control of Anabolic Resistance in Aging Muscle

This is an interventional study enrolling older individuals aged 60-85y to observe changes during physical inactivity. This study is investigating the relation between short-term physical inactivity and the impact of muscle health and function. The enrollment goal is 8 participants. The study will occur over the course of a month where participants will undergo testing before and after a reduction in physically activity levels. There will be a screening event collecting baseline data, two body composition scans, muscle function and oral glucose tolerance tests and a metabolic study before and after a 2-week period of inactivity. Each metabolic study will entail three-muscle biopsies: one before and 2 after the ingestion of leucine.

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.

Eligibility Criteria:
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