Translational Control of Anabolic Resistance in Aging Muscle

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Translational Control of Anabolic Resistance in Aging Muscle

Conditions
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Physical Inactivity

Intervention / Treatment
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* Other: Reduced Physical Activity


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 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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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: Participants will be tested before and 2-weeks after they have reduced their level of physical activity
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reduced Physical Activity<br>Participants will reduce their physical activity levels for 2-weeks by approximately 75% of their baseline level of physical activity | Other: Reduced Physical Activity<br>* Participants will reduce their level of physical activity for 2-weeks as defined as approximately 75% reduction from their baseline level of physical activity.<br>* Other names: Muscle Disuse;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lean Mass | Change in lean mass | baseline and 2-weeks | 
| Strength | Change in muscle strength | baseline and 2-weeks |