Nutrient Regulation of Amino Acid Transporters in Aging Human Skeletal Muscle
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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.
amino acid transporter [ Time Frame: before and after (1 and 3h) amino acid ingestion. These samples will be taken before bed rest and 7 days after bed rest. ]
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.
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Ages Eligible for Study:
18 Years to 75 Years (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
young and older healthy humans
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
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