Nutrient Regulation of Amino Acid Transporters in Aging Human Skeletal Muscle

Nutrient Regulation of Amino Acid Transporters in Aging Human Skeletal Muscle

The goal of the research project is to determine how aging and inactivity reduce the muscle anabolic effect of nutrients and lead to muscle and functional loss. The central hypothesis is that aging reduces mTORC1 signaling and the expression of skeletal muscle amino acid transporters in response to anabolic stimulation leading to reduced muscle adaptation to increased intracellular amino acid requirements. The investigators further hypothesize that inactivity exacerbates this effect with significant muscle and functional loss, and rehabilitation restores muscle signaling, metabolism and function to baseline values.

Inclusion Criteria:

1 . Age between 18-35 and 60-75 yrs 2. Ability to sign informed consent 3. Mini-mental state exam score >26 4. Free-living, prior to admission

Exclusion Criteria:

1. Cardiac abnormalities considered exclusionary by the study physician (e.g., CHF, CAD, right-to-left shunt)
2. Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes)
3. GFR <65 mL/min/1.73m2 or evidence of kidney disease or failure
4. 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)
5. Risk of DVT including family history of thrombophilia, DVT, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL), and connective tissue diseases (positive lupus anticoagulant), hyperhomocysteinemia, deficiencies of factor V Leiden, proteins S and C, and antithrombin III
6. Use of anticoagulant therapy. (e.g., Coumadin, heparin)
7. Prior history of Heparin-Induced Thrombocytopenia (HIT)
8. Elevated systolic pressure >150 or a diastolic blood pressure > 100
9. Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators)
10. Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
11. Currently on a weight-loss diet or body mass index > 30 kg/m2
12. Inability to abstain from smoking for duration of study
13. A history of > 20 pack per year smoking
14. HIV or hepatitis B or C*
15. Recent anabolic or corticosteroids use (within 3 months)
16. Subjects with hemoglobin or hematocrit lower than accepted lab values
17. Agitation/aggression disorder (by psychiatric history and exam)
18. History of stroke with motor disability
19. A recent history (<12 months) of GI bleed
20. Pregnancy as determined by a pregnancy test
21. Depression [>5 on the 15 items Geriatric Depression Scale (GDS)]
22. Alcohol or drug abuse
23. Exercise training (>1 session of moderate to high intensity aerobic or resistance exercise/week)
24. Liver disease (AST/ALT 2 times above the normal limit, hyperbilirubinemia)
25. Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation <97% on room air)
26. Any other condition or event considered exclusionary by the PI and faculty physician