Mitochondria and Muscle Health in Elderly

Completed

• Conditions: Muscle Weakness

• Registration Number: NCT03666013
• Lead Sponsor: Maastricht University

Brief Summary

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

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.

Study Timeline

• Study Start: 2017-06-27
• Study First Submitted: 2018-09-04
• Study First Submitted QC: 2018-09-07
• Study First Posted: 2018-09-11
• Primary Completion: 2019-10-01
• Status Verified: 2021-04
• Study Completion: 2021-04-09
• Last Update Submitted: 2021-04-19
• Last Update Posted: 2021-04-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 59

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of ex vivo mitochondrial State 3 respiration	Day 4	Ex vivo mitochondrial capacity, ADP-stimulated respiration expressed by O2flux in pmol/mg wet weight/second

Secondary Outcome Measures

Name	Time	Method
Insuline sensitivity	Day 1	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
Body composition	Day 3	Measured by BodPod and expressed by percentages of fat mass (%)
Muscle strength in upper-leg	Day 3	Extensor and flexor muscles of the knee joint measured by dynamometer (Biodex) expressed in peak torque 70° extension and flexion knee (Nm/kg)
Muscle metabolism in vivo (H-MRS acetylcarnitine)	Day 5	In vivo skeletal muscle acetylcarnitine concentrations in rest measured by H-MRS and expressed by mmol/kgww
Muscle volume upper-leg	Day 5	Muscle volume measured by MRI
Physical functionality, 6MWT	Day 2	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
VO2max	Day 2	Maximal oxygen uptake measured by maximal cycling test (ml\*kg-1\*min-1)
Dynamic gait stability	Day 3	Characterized by using the CAREN-system locomotion assessment and expressed by amount of steps necessary to regain normal walking pattern
Muscle oxidative capacity in vivo (PCr-MRS recovery)	Day 5	In vivo skeletal muscle PCr-recovery expressed by PCr halftime (s)
Energy expenditure in rest and during sub-maximal exercise	Day 4	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)

Trial Locations

Locations (1)

Maastricht University; 🇳🇱 Maastricht, Limburg, Netherlands