Endurance training and detraining in mitochondrial myopathies due to single large-scale mtDNA deletions
Open accessAbstract
At present there are limited therapeutic interventions for patients with mitochondrial myopathies. Exercise training has been suggested as an approach to improve physical capacity and quality of life but it is uncertain whether it offers a safe and effective treatment for patients with heteroplasmic mitochondrial DNA (mtDNA) mutations. The objectives of this study were to assess the effects of exercise training and detraining in eight patients with single, large-scale mtDNA deletions to determine: (i) the efficacy and safety of endurance training (14 weeks) in this patient population; (ii) to determine the effect of more prolonged (total of 28 weeks) exercise training upon muscle and cardiovascular function and (iii) to evaluate the effect of discontinued training (14 weeks) upon muscle and cardiovascular function. Our results show that: (i) 14 weeks of exercise training significantly improved tolerance of submaximal exercise and peak capacity for work, oxygen utilization and skeletal muscle oxygen extraction with no change in the level of deleted mtDNA; (ii) continued training for an additional 14 weeks maintained these beneficial adaptations; (iii) the cessation of training (detraining) resulted in loss of physiological adaptation to baseline capacity with no overall change in mutation load. Patients' self assessment of quality of life as measured by the SF-36 questionnaire improved with training and declined with detraining. Whilst our findings of beneficial effects of training on physiological outcome and quality of life without increases in the percentage of deleted mtDNA are encouraging, we did not observe changes in mtDNA copy number. Therefore there remains a need for longer term studies to confirm that endurance exercise is a safe and effective treatment for patients with mitochondrial myopathies. The effects of detraining clearly implicate physical inactivity as an important mechanism in reducing exercise capacity and quality of life in patients with mitochondrial myopathy.
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Although oxidative capacity is improved by exercise, there are no changes in the mtDNA mutation load.
“However, others have reported that although oxidative capacity is improved, there are no changes in the mtDNA mutation load (Jeppesen et al., 2009; Taivassalo et al., 2006).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Taivassalo et al., 2006
Endurance training for up to 14 weeks improves OXPHOS function, but does not shift mutated mtDNA levels in muscle, and cessation causes loss of physiological adaptations.
“Well tolerated and safe, endurance training for up to 14 weeks has been found to improve OXPHOS function, although no concomitant shift in mutated mtDNA levels in muscle has been observed and cessation in training does cause a loss of the physiological adaptations [228][229][230].”
From Mitochondrial DNA mutations and human disease (2010) · cites this paper as [230]
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- Authors
- Taivassalo, T., Gardner, J. L., Taylor, R. W., Schaefer, A. M., Newman, J., Barron, M. J., Haller, R. G., & Turnbull, D. M.
- Affiliations
- McGill University (CA)
- Newcastle University (GB)
- Texas Health Dallas (US)
- Corresponding author
- Taivassalo, T.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-06-09
- Volume
- 129
- Issue
- 12
- Pages
- 3391-3401
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2130183664
- Cited by
- 220
- References
- 23
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 11 · 2023: 5 · 2022: 12 · 2021: 14 · 2020: 11 · 2019: 12 · 2018: 6 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 13 · 2013: 16 · 2012: 15
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Brain (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Muscular Dystrophy Association
- United Mitochondrial Disease Foundation
- Wellcome Trust (074454/Z/04/Z)
- Muscular Dystrophy UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- mitochondrial myopathy, mitochondrial DNA deletions, endurance training, detraining, exercise training, exercise capacity, oxygen utilization, cardiovascular function, quality of life, physical inactivity, exercise therapy
- MeSH terms
- Adaptation, Physiological, Adult, Electron Transport Complex IV, DNA, Mitochondrial, Exercise Test, Exercise Therapy, Physical Exertion, Female, Heart Rate, Humans, Lactates, Male, Middle Aged, Oxygen, Patient Compliance, Physical Endurance, Quality of Life, Polymerase Chain Reaction, Treatment Outcome, Mitochondrial Myopathies, Gene Deletion, Muscle, Skeletal, Muscle Fibers, Skeletal
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