Mitochondria and Muscle Health in Elderly

Study Overview
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Brief Summary
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The aim of this study is to characterize the relation between skeletal muscle mitochondrial metabolism and muscle health in elderly, physically compromised humans. To study this relation, a cross-sectional study will be performed in well-defined, distinct subject groups. Thus, to obtain insight in the relation between mitochondrial health and muscle function, not only subjects that differ in mitochondrial function (based on physical activity) will be compared but also subjects with high- versus low muscle function will be selected.

Detailed Description
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Aging is associated with a decline of mitochondrial and skeletal muscle volume, -quality and -function. If a causal link exists between the loss of mitochondrial function and muscle health is unknown, however, both appear with advancing age and are associated with the loss of functional capacity, which increases comorbidities and annual healthcare costs. The aim is to test the hypothesis that a compromised muscle function in sedentary elderly is related to an impaired mitochondrial health. A detailed characterization of mitochondrial metabolism and muscle function is performed in well-defined, (physically compromised) elderly humans, in a cross-sectional design. To obtain insight in the relation between mitochondrial health and muscle function, not only elderly subjects that differ in mitochondrial function (based on physical activity) will be compared but also elderly subjects with high versus low muscle physical function will be selected. Healthy, young (20-30 years,) individuals with normal physical activity levels will be included as absolute controls.

Official Title
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Mitochondrial Health and Muscle Function in Elderly

Conditions
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Muscle Weakness

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females Subject should be in sufficient health to participate in the experimentations, to be judged by the responsible MD based on the subject's medical history Caucasian origin (see study groups) Exclusion Criteria: Any contraindications for MRI scan: Aneurysm clips Implanted neural stimulator Implanted cardiac pacemaker of defibrillator Cochlear implant Iron- containing corpora aliena in the eye or brain Artificial (heart) valves which is contraindicated for MRS Claustrophobia Diagnosed with diabetes mellitus Poor health as judged by the responsible medical doctor Heart problems: In case of an abnormal ECG in rest, this will be discussed with both the participant and the responsible medical doctor

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 80 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 |
| --- | --- |
| Young healthy subjects<br>20-30 years old, max 1h of exercise per week | |
| Elderly with a normal physical function<br>65-80 years old, max 1h of exercise per week | |
| Elderly with a decreased physical function<br>65-80 years old, max 1h of exercise per week, SPPB under 9 or frailty score lower then 10 | |
| Active elderly<br>65-80 years old, minimal 3h of exercise per week | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of ex vivo mitochondrial State 3 respiration | Ex vivo mitochondrial capacity, ADP-stimulated respiration expressed by O2flux in pmol/mg wet weight/second | Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insuline sensitivity | Measured by 1-step hyperinsulinemic euglycemic. Insulin-stimulated glucose disposal, expressed as the rate of disappearance of the glucose (Rd glucose in μmol*kg-1*bw*min-1 | Day 1 | 
| Physical functionality, 6MWT | Measured by a standardized 6-minute walk test. Physical functionality expressed in the distance (in meters) the subject is able to walk over a total of six minutes | Day 2 | 
| VO2max | Maximal oxygen uptake measured by maximal cycling test (ml*kg-1*min-1) | Day 2 | 
| Body composition | Measured by BodPod and expressed by percentages of fat mass (%) | Day 3 | 
| Dynamic gait stability | Characterized by using the CAREN-system locomotion assessment and expressed by amount of steps necessary to regain normal walking pattern | Day 3 | 
| Muscle strength in upper-leg | Extensor and flexor muscles of the knee joint measured by dynamometer (Biodex) expressed in peak torque 70° extension and flexion knee (Nm/kg) | Day 3 | 
| Energy expenditure in rest and during sub-maximal exercise | indirect calorimetry during 45 minutes in resting state (in KJ/min) and 1-hour exercise bout at 50% of maximal power output (in KJ/min) | Day 4 | 
| Muscle oxidative capacity in vivo (PCr-MRS recovery) | In vivo skeletal muscle PCr-recovery expressed by PCr halftime (s) | Day 5 | 
| Muscle metabolism in vivo (H-MRS acetylcarnitine) | In vivo skeletal muscle acetylcarnitine concentrations in rest measured by H-MRS and expressed by mmol/kgww | Day 5 | 
| Muscle volume upper-leg | Muscle volume measured by MRI | Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitochondrial health, Muscle function, Aging