Mitochondria and Muscle Health in Elderly (ELMIH)

Mitochondrial Health and Muscle Function in Elderly

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.

Study Overview

• Status: Completed
• Conditions: Muscle Weakness

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 Type: Observational
• Enrollment (Actual): 59

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6200 MD
      • Maastricht University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 80 years (Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers between 20 and 30 years old and 65 and 80 years old

Description

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 Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Young healthy subjects; 20-30 years old, max 1h of exercise per week
Elderly with a normal physical function; 65-80 years old, max 1h of exercise per week
Elderly with a decreased physical function; 65-80 years old, max 1h of exercise per week, SPPB under 9 or frailty score lower then 10
Active elderly; 65-80 years old, minimal 3h of exercise per week

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University
• Collaborators: Top Institute Food and Nutrition; Netherlands Organisation for Scientific Research
• Investigators: Principal Investigator: Patrick Schrauwen, Prof . dr., Maastricht University

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2017
• Primary Completion (Actual): October 1, 2019
• Study Completion (Actual): April 9, 2021

Study Registration Dates

• First Submitted: September 4, 2018
• First Submitted That Met QC Criteria: September 7, 2018
• First Posted (Actual): September 11, 2018

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Aging; Muscle function; Mitochondrial health
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Weakness
• Other Study ID Numbers: Mitohealth

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No