Aging, Muscle Atrophy or Weakness, Sarcopenia, Sarcopenia in Elderly
Conditions
Keywords
muscle, aging, elderly, myosin, protein, sarcomere, exercise, function, atrophy, contractile, strength, balance, mobility, MyBP-C, fiber, biopsy, skeletal muscle, fatigue
Brief summary
This study is investigating changes to the proteins in skeletal muscle that contribute to reduced muscle size and muscle function that occurs with aging.
Detailed description
Age-related muscle atrophy and contractile dysfunction have been well described at the cellular level, but the molecular mechanisms that contribute to this dysfunction are poorly understood. Improved understanding of these mechanisms is critically important for the improvement of physical rehabilitation in older adults at risk for mobility impairment and physical disability. Our studies will pursue pre-clinical evidence that post translational modification of specific proteins in skeletal muscle lead to an "aging phenotype" in skeletal muscle that may unlock new strategies for improving physical function in older adults with physical frailty.
Interventions
BEHAVIORALFatiguing Exercise
Volunteers will perform knee extension exercise of the dominant limb while seated in a chair designed for exercise of the knee extensor muscle group. The chair will be equipped with a lever arm, aligned with the axis of rotation of the knee and fixed to the distal shank, 2 centimeters proximal to the ankle joint. The lever arm will be instrumented to provide resistance and measure velocity. The volunteers will perform 3-5 maximum voluntary contractions (MVC) to determine peak torque. Once established, volunteers will rest for 5 minutes before initiating the fatigue protocol, whereby they will perform repeated MVC of the dominant limb against resistance equal to or less than 50% of MVC until range of motion cannot be maintained. Because the goal of this exercise is to uniformly fatigue the quadriceps muscle group, this exercise will be performed continuously. It is expected to take between 1 and 3 minutes to achieve the desired level of fatigue.
Sponsors
University of Oregon
Wu Tsai Human Performance Alliance
National Institutes of Health (NIH)
Oregon Health and Science University
Washington State University
National Institute on Aging (NIA)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults between the ages 18-35 or 65-80 years * Healthy by self-report * Willing to participate in all aspects of the study design including muscle biopsy, unilateral exercise, and physical activity monitoring * Fluent in English (due to lack of translation services, it is not practical to conduct the study using a language other than English).
Exclusion criteria
* Orthopaedic limitation (severe knee osteoarthritis, prior joint replacement, etc.). * Volunteer has dementia or related mental issues that potentially put the subject at risk as determined by prior diagnosis. * Volunteer has known untreated endocrine disease (hypo/hyper thyroidism, Addison's Disease or Cushing's syndrome, etc.) * Volunteer has untreated/poorly-controlled hypertension (stage 2, per American College of Cardiology \[\>140/90 mmHg\]). * Volunteer has significant heart, liver, kidney or respiratory disease. * Volunteer has diabetes (insulin dependent or non-insulin dependent). * Volunteer has known coagulopathies. * Volunteer has taken anabolic steroids in the prior six months. * Volunteer has received treatment for cancer (other than effective Mohs Surgery for successful removal of basal cell or squamous cell carcinomas) * Unexpected weight loss \>5kg is last 12 months * Volunteer is an active smoker or quit within the last year. * Volunteer has known current alcohol or drug use disorder (AUD; defined as binge drinking of \>4 days in the last month. Binge drinking is \>5 drinks for men and \>4 drinks for women, per occasion). Or, if a volunteer reports drinking in excess of "low risk" per NIAAA (\>7 drinks/week for men and \>3 drinks/day for women and \>14 drinks/week and \>4 drinks/day). * Volunteer has a diagnosed neuromuscular disorder. * Volunteer has allergy to lidocaine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phosphorylation of myosin binding protein c (MyBP-C) | One week after the participant undergoes the biopsies. | Muscle tissue is immediately frozen after biopsy. Liquid chromatography and high resolution mass spectrometry will be used to do a full analysis of the phosphorylation sites on MyBP-C isolated from the biopsied muscle tissue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Muscle fiber Force | Within three weeks of the intervention and biopsies. | Ex vivo assessment of Force (mN) will be performed on muscle fibers and bundles isolated from fatigued and non-fatigued muscle biopsies. |
| Muscle fiber Tension | Within three weeks of the intervention and biopsies. | Ex vivo assessment of Tension (kPa) will be performed on muscle fibers and bundles isolated from fatigued and non-fatigued muscle biopsies. |
| Muscle fiber Velocity | Within three weeks of the intervention and biopsies. | Ex vivo assessment of Velocity (Lo/s) will be performed on muscle fibers and bundles isolated from fatigued and non-fatigued muscle biopsies. |
| Muscle fiber Power | Within three weeks of the intervention and biopsies. | Ex vivo assessment of Power (w/L) will be performed on muscle fibers and bundles isolated from fatigued and non-fatigued muscle biopsies. |
Countries
United States
Contacts
CONTACTDamien M Callahan, Ph.D.
CONTACTKaren Wiedenfeld Needham, BS
PRINCIPAL_INVESTIGATORDamien M Callahan, Ph.D.
University of Oregon
Outcome results
None listed