Atrophy of Muscle Due to Disuse, Rehabilitation
Conditions
Brief summary
This project is a 2-phase, randomized clinical trial that includes 7 days of unilateral leg disuse (Phase 1), immediately followed by 1 week of bilateral leg rehabilitation (Phase 2). The investigators will recruit cohorts of healthy middle-aged men and women to address their aims: * Demonstrate the sex-specific effects of skeletal muscle disuse (Phase 1) * Identify key molecular determinates of susceptibility of skeletal muscle atrophy (Phase 1) * Map the early, sex-specific molecular time-course of rehabilitation (Phase 2) * Determine if disused and healthy muscle respond similarly to exercise (Phase 2) Healthy, middle-age men and post-menopausal women (50-65 years) will be recruited from the greater Houston/Galveston area. This under-represented research demographic demonstrate few negative metabolic or phenotypic signs of advanced age, but are at increased risk of being hospitalized and experiencing accelerated loss of lean mass and muscle function that parallels a much older population. The goal of this study is to characterize phenotypic and molecular skeletal muscle changes in middle-aged men and women during critical periods of disuse and rehabilitation and ultimately direct the development of targeted and effective prevention and treatment strategies.
Detailed description
The negative health consequences of muscular disuse in aging populations are unequivocal. While descriptive, outcome data on disuse and recovery are abundant, key knowledge gaps limit researcher's ability to implement evidence-based, rehabilitation strategies. Limiters include: i) an inability to identify individuals most susceptible to disuse, ii) insufficient information to differentiate between, and respond to, disuse atrophy in men and women, iii) limited insight into the mechanisms driving adaptation to early rehabilitative exercise, and iv) the assumption that disused and healthy skeletal muscle will have a similar, positive response to resistance exercise. The investigators will complete a 2-phase, randomized clinical trial. The protocol includes 7-days of unilateral leg disuse (ULD; Phase 1), immediately followed by 1 week of bilateral leg rehabilitation (Phase 2). Healthy, middle-aged men (n=40) and (post-menopausal) women (n=40), (50-65 y) will be recruited; a neglected research demographic who present with a largely youthful phenotype, but are at risk of accelerated disuse atrophy. This project will provide a highly powered, detailed phenotypic characterization of the continuum of adults most and least susceptible to muscular disuse. Clinical outcomes will be supported by RNA deep sequencing and pathway analysis to establish a platform that: i) improves scientists' ability to identify higher-risk individuals and ii) provides insight into time-sensitive, sex-specific and effective rehabilitation strategies. Findings and reposed molecular data from this study, may help identify future therapeutic targets and serve as an uncomplicated/comorbidity-free baseline for clinical trials in populations experiencing disuse atrophy.
Interventions
OTHERResistance Exercise Rehabilitation
Following disuse, the REHAB groups (M-REHAB, F-REHAB) will complete monitored resistance exercise rehabilitation sessions using an isokinetic dynamometer at a similar relative load at each rehab visit.
OTHERWalking-based rehabilitation
Following disuse, the CON groups (M-CON, F-CON) will complete 30 minutes of monitored walking at a moderate intensity at each rehab visit.
Sponsors
The University of Texas Health Science Center at San Antonio
National Institute on Aging (NIA)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
50 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. All races and ethnic backgrounds 2. Men and women, age 50-65 years 3. Generally healthy (see
Exclusion criteria
) 4. Able and willing to provide informed consent 5. Ability to speak and read English 6. Post-menopausal women (no menses within the last 12 months) 7. Body mass index: 18.5-35 kg/m2 or BMI\>35 if thigh adiposity does not impair muscle biopsy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quantitative RNA-sequencing | Study day 1 (before starting leg disuse) | RNA deep sequence analysis on muscle tissue taken from a muscle biopsy to measure transcriptome |
| Muscle function | Study day 1 (before starting leg disuse) | Each leg will be individually tested on an isokinetic dynamometer to determine muscle strength (peak torque) |
| Body (leg) composition | Study day 1 (before starting leg disuse) | Leg lean mass will be assessed via segmental dual energy x-ray absorptiometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle fiber cross sectional area | Study day 1 (before starting leg disuse) | Muscle biopsy samples will be evaluated for muscle fiber cross sectional area |
| Muscle fiber type | Study day 1 (before starting leg disuse) | Muscle biopsy samples will be evaluated for muscle fiber type distribution |
| Diet recall | Familiarization session (~1 week before starting leg disuse) | A multi-pass 24-hour dietary recall using the Automated Self Assessment 24-h dietary assessment tool to determine habitual food intake |
| Physical activity | Study Days -7 to Day 0 (1 week prior to starting leg disuse) | Accelerometers will placed on the waist and ankle to measure physical activity |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORBlake Rasmussen, PhD
University of Texas Health Science Center as San Antonio
Outcome results
None listed