Nutrient Regulation of Amino Acid Transporters in Aging Human Skeletal Muscle

Study Overview
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Brief Summary
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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.

Official Title
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Nutrient Regulation of Amino Acid Transporters in Aging Human Skeletal Muscle

Conditions
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Healthy

Participation Criteria
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Eligibility Criteria
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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: Cardiac abnormalities considered exclusionary by the study physician (e.g., CHF, CAD, right-to-left shunt) Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, diabetes) GFR <65 mL/min/1.73m2 or evidence 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 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 Use of anticoagulant therapy. (e.g., Coumadin, heparin) Prior history of Heparin-Induced Thrombocytopenia (HIT) Elevated systolic pressure >150 or a diastolic blood pressure > 100 Implanted electronic devices (e.g., pacemakers, electronic infusion pumps, stimulators) Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma Currently on a weight-loss diet or body mass index > 30 kg/m2 Inability to abstain from smoking for duration of study A history of > 20 pack per year smoking HIV or hepatitis B or C* Recent anabolic or corticosteroids use (within 3 months) Subjects with hemoglobin or hematocrit lower than accepted lab values Agitation/aggression disorder (by psychiatric history and exam) History of stroke with motor disability A recent history (<12 months) of GI bleed Pregnancy as determined by a pregnancy test Depression [>5 on the 15 items Geriatric Depression Scale (GDS)] Alcohol or drug abuse Exercise training (>1 session of moderate to high intensity aerobic or resistance exercise/week) Liver disease (AST/ALT 2 times above the normal limit, hyperbilirubinemia) Respiratory disease (acute upper respiratory infection, history of chronic lung disease with resting oxygen saturation <97% on room air) Any other condition or event considered exclusionary by the PI and faculty physician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| old (60-75yr)<br> | |
| young (18-35y)<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| amino acid transporter | Muscle biopsies will be sampled from the vastus laterals before amino acid ingestion and then 1 and 3h after amino acid ingestion. Muscle biopsies will be processed using western blotting and gene expression to assess the expression of specific amino acid transporters. The investigators are interested in the change in expression of amino acid transporters in response to amino acid ingestion from baseline. The response before bed rest will be compared to after bed rest. | before and after (1 and 3h) amino acid ingestion. These samples will be taken before bed rest and 7 days after bed rest. |