About this trial
The goal of this observational study is to learn how exercise training affects molecular processes in skeletal muscle in adults with mitochondrial myopathy, compared with healthy adults.
The main questions it aims to answer are:
* How does exercise training affect mitochondrial activity and energy production pathways in skeletal muscle in people with mitochondrial myopathy? * How does exercise training affect molecular signals related to muscle growth, stress responses, and muscle-nerve communication in people with mitochondrial myopathy?
Researchers will compare the trained leg to the untrained leg within the same participant, and also compare responses between participants with mitochondrial myopathy and healthy control participants, to see how molecular responses to exercise differ between groups.
The participants will:
* Complete a 3-4-week supervised exercise training program using one leg. * Undergo muscle biopsies from both the trained and untrained leg. * Complete basic muscle strength and physical function tests.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Known mtDNA or nuclear (nDNA) mutations
Age above or equal to 18 years
Disqualifiers
Medical conditions which deem the MM patient unfit to complete the study
Current use of medications known to interact with outcome measures. (see below)
Pregnancy
The participant is for any other reason unlikely to complete the study
Trial design
Parallel
Treatments tested in this trial
Unilateral high-intensity interval training (HIIT)
BehavioralParticipants will undergo ten sessions of HIIT of the leg randomized to the intervention while the inactive leg serves as the control leg
Treatment groups
Trial outcomes
Primary outcomes
Muscle mitochondrial respiration
Mitochondrial O2 flux is measured by high-resolution respirometry in permeabilized fibers from muscle biopsy samples after either exercise or ususal physical activity
Muscle mitochondrial reactive oxygen species (ROS) production
Mitochondrial H2O2 emission rates are measured by high-resolution fluorometry in permeabilized fibers from muscle biopsy samples after either exercise or ususal physical activity
Secondary outcomes
Muscle strength and endurance
Measured by an incremental one-legged test.
Muscle structure and neuromuscular junction morphology
Measured by histology and TEM from muscle biopsy specimens taken from both trained and untrained leg
Muscle integrated stress responses, growth and metabolic signaling
Measured by immunoblotting and Real-Time PCR in muscle biopsies from trained and untrained leg
Body and leg composition
as measured by whole-body DXA scanning
Other outcomes
Global unbiased exploratory metabolomic, lipidomic, proteomic, and microRNA profiling
From trained and untrained muscle biopsy samples from individuals with MM and matched healthy control subjects
Sponsors and contacts
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University of Copenhagen
Lead sponsor
Rigshospitalet, Denmark
Collaborator