Sarcopenia
Conditions
Brief summary
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:
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
University of Florida
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Satellite Cells | Baseline, 2 days post-injury, 7 days post-injury | 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. |
Countries
United States
Participant flow
Recruitment details
From September 2010 through December 2011, community-dwelling persons were recruited to participate through a variety of methods including media articles, direct mailings, newspaper announcements, and presentations to community groups.
Participants by arm
| Arm | Count |
|---|---|
| Older Adults | 39 |
| Young Adults | 29 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not quality after 2nd screening | 14 | 1 |
| Overall Study | Lost to Follow-up | 0 | 7 |
| Overall Study | Physician Decision | 2 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 6 |
Baseline characteristics
| Characteristic | Older Adults | Young Adults | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 39 Participants | 0 Participants | 39 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 29 Participants | 29 Participants |
| Region of Enrollment United States | 39 participants | 29 participants | 68 participants |
| Sex: Female, Male Female | 15 Participants | 11 Participants | 26 Participants |
| Sex: Female, Male Male | 24 Participants | 18 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 29 | 7 / 39 |
| serious Total, serious adverse events | 0 / 29 | 2 / 39 |
Outcome results
Primary
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.
Time frame: Baseline, 2 days post-injury, 7 days post-injury
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Older Adults | Muscle Satellite Cells | Adjusted Baseline | 3.2 Number of Pax7+ cells/muscle fiber | Standard Error 0 |
| Older Adults | Muscle Satellite Cells | Adjusted 2 days post-injury | 4.0 Number of Pax7+ cells/muscle fiber | Standard Error 0.4 |
| Older Adults | Muscle Satellite Cells | Adjusted 7 days post-injury | 4.0 Number of Pax7+ cells/muscle fiber | Standard Error 0.3 |
| Young Adults | Muscle Satellite Cells | Adjusted Baseline | 3.2 Number of Pax7+ cells/muscle fiber | Standard Error 0 |
| Young Adults | Muscle Satellite Cells | Adjusted 2 days post-injury | 3.8 Number of Pax7+ cells/muscle fiber | Standard Error 0.4 |
| Young Adults | Muscle Satellite Cells | Adjusted 7 days post-injury | 3.7 Number of Pax7+ cells/muscle fiber | Standard Error 0.3 |