Blood Flow, Muscle Regeneration and Sarcopenia

Study Overview
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Brief Summary
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Due to the rapid aging of the population, sarcopenia is among the greatest challenges facing the health care system over the next quarter century. This age-related loss of skeletal muscle mass and strength directly contributes to the incidence of functional disability, thereby reducing independence and quality of life for the elderly. Despite increasing efforts to combat sarcopenia, its etiology remains incompletely described. Subsequently, limited progress has been made in developing comprehensive preventative and therapeutic strategies to combat the problem. A decreased ability to regenerate skeletal muscle fibers through the donation of skeletal muscle stem cells (satellite cells) is thought to contribute to sarcopenia. However, the upstream physiological mediators that regulate this impairment are poorly delineated. Reduced muscle blood flow in advanced age appears to be a significant factor in reducing skeletal muscle regenerative capacity, but few data exist to confirm this hypothesis. Thus to test this hypothesis we aim to conduct a translational pilot trial which examines regeneration in both young and old adults. Furthermore, we aim to determine if muscle blood flow and satellite cell number are associated with muscle function. The central hypothesis of this proposal is that age-related declines in skeletal muscle angiogenesis and perfusion are significant causal factors in age-related losses of skeletal muscle mass. The specific aims and hypotheses of the project are as follows:

Official Title
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Role of Skeletal Muscle Blood in Muscle Regeneration and Sarcopenia

Conditions
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Sarcopenia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women aged 18-30 years Men and women aged > 70 years Body mass index < 35 Willing and able to participate in all aspects of the study Sedentary to moderately active lifestyle <120 min physical activity/week < 30 min moderate aerobic exercise/week < 30 min resistance training/week OR Participates in regular structured exercise > 120 min/week Non-smoking Exclusion Criteria: Active treatment for cancer, stroke (< 6 mo), peripheral vascular disease, coronary artery disease (myocardial infarction <6 mo), state III, IV Congestive Heart Failure, valvular heart disease, major psychiatric disease, severe anemia, liver or renal disease, diabetes, severe osteoarthritis, blindness or deafness, fracture in upper or lower extremity within the last 6 months, upper or lower extremity amputation, anticoagulant therapy (aspirin use is permitted), parkinsons disease Failure to give consent Anabolic medications (growth hormone or testosterone) High amounts of physical activity (i.e. running, bicycling etc > 120 min/week). Dementing illness Smoking Pregnant Significant cognitive impairment; Mini-Mental State (MMSE) exam < 24 Statin Usage Excessive alcohol use (>2 drinks per day) Resting heart rate > 120 bpm Systolic blood pressure > 180 mmHg Diastolic blood pressure > 110 mmHg History of significant head injury Anticholinesterase inhibitor (such as Aricept) Contraindications to MRI (e.g. cardiac pacemaker, implanted cardiac defibrillator, aneurysm clip, claustrophobia, etc.) Current Use of Antidepressant Medications

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Older Adult<br>Healthy Men and Women Over 70 Years of Age | |
| Young Adult<br>Healthy Men and Women Aged 18-30 Years | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Satellite Cells | Change in the number of myonuclear cells identified as Pax7+ following contraction-induced skeletal muscle injury. Cells identified as Pax7+ by immunohistochemistry of skeletal muscle biopsy samples. Data adjusted for gender, physical activity level, and baseline satellite cell number. | Baseline, 2 days post-injury, 7 days post-injury |