Whole-body and muscle responses to aerobic exercise training and withdrawal in ageing and COPD
Open accessAbstract
Background: Chronic obstructive pulmonary disease (COPD) patients exhibit lower peak oxygen uptake (V′O 2peak), altered muscle metabolism and impaired exercise tolerance compared with age-matched controls. Whether these traits reflect muscle-level deconditioning (impacted by ventilatory constraints) and/or dysfunction in mitochondrial ATP production capacity is debated. By studying aerobic exercise training (AET) at a matched relative intensity and subsequent exercise withdrawal period we aimed to elucidate the whole-body and muscle mitochondrial responsiveness of healthy young (HY), healthy older (HO) and COPD volunteers to whole-body exercise. Methods: HY (n=10), HO (n=10) and COPD (n=20) volunteers were studied before and after 8 weeks of AET (65%V′O 2peak) and after 4 weeks of exercise withdrawal.V′O 2peak, muscle maximal mitochondrial ATP production rate (MAPR), mitochondrial content, mitochondrial DNA (mtDNA) copy number and abundance of 59 targeted fuel metabolism mRNAs were determined at all time-points. Results: Muscle MAPR (normalised for mitochondrial content) was not different for any substrate combination in HO, HY and COPD at baseline, but mtDNA copy number relative to a nuclear-encoded housekeeping gene (mean±sd) was greater in HY (804±67) than in HO (631±69; p=0.041). AET increased V′O 2peak in HO (17%; p=0.002) and HY (21%; p<0.001), but not COPD (p=0.603). Muscle MAPR for palmitate increased with training in HO (57%; p=0.041) and HY (56%; p=0.003), and decreased with exercise withdrawal in HO (−45%; p=0.036) and HY (−30%; p=0.016), but was unchanged in COPD (p=0.594). mtDNA copy number increased with AET in HY (66%; p=0.001), but not HO (p=0.081) or COPD (p=0.132). The observed changes in muscle mRNA abundance were similar in all groups after AET and exercise withdrawal. Conclusions: Intrinsic mitochondrial function was not impaired by ageing or COPD in the untrained state. Whole-body and muscle mitochondrial responses to AET were robust in HY, evident in HO, but deficient in COPD. All groups showed robust muscle mRNA responses. Higher relative exercise intensities during whole-body training may be needed to maximise whole-body and muscle mitochondrial adaptation in COPD.
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Whether the effects of exercise are the same in aged individuals as opposed to adults with obesity remains equivocal and is likely influenced by long-term diet and physical activity patterns.
“Whether these effects of exercise are the same in aged individuals, as opposed to adults with obesity remains equivocal [110–112] and is likely influenced by long-term diet and physical activity patterns.”
From Targeting Intramyocellular Lipids to Improve Aging Muscle Function (2025) · cites this paper as [112]
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Targeting Intramyocellular Lipids to Improve Aging Muscle Function
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“Whether these effects of exercise are the same in aged individuals, as opposed to adults with obesity remains equivocal [110–112] and is likely influenced by long-term diet and physical activity patterns.”
- Authors
- Latimer, L. E., Constantin-Teodosiu, D., Popat, B., Constantin, D., Houchen-Wolloff, L., Bolton, C. E., Steiner, M. C., & Greenhaff, P. L.
- Affiliations
- University of Leicester (GB)
- Nottingham University Hospitals NHS Trust (GB)
- Corresponding author
- Greenhaff, Paul L.
- Venue
- European Respiratory Journal
- Publisher
- European Respiratory Society (ERS)
- Published
- 2021-09-29
- Volume
- 59
- Issue
- 5
- Pages
- 2101507
- ISSN
- 0903-1936 (ISSN-L)
- 1399-3003
- PMC
- PMC9095946
- OpenAlex
- W3204117377
- Cited by
- 14
- References
- 40
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 1 · 2022: 3
- FWCI
- 1.69
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- European Respiratory Journal (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Funders
- Medical Research Council (MRC)-Versus Arthritis Centre for Musculoskeletal Ageing Research (MR/K00414X/1)
- NIHR Nottingham Biomedical Research Centre
- COPDMAP: The COPD MRC/ABPI Partnership
- Arthritis Research UK (19891)
- NIHR Leicester Biomedical Research Centre
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- chronic obstructive pulmonary disease, aerobic exercise training, exercise withdrawal, aging, mitochondrial ATP production, mitochondrial DNA copy number, peak oxygen uptake, exercise tolerance, muscle deconditioning, palmitate oxidation, mitochondrial content, older adults, ventilatory constraints
- MeSH terms
- Adenosine Triphosphate, Aging, DNA, Mitochondrial, Exercise Test, Humans, Muscles, Oxygen Consumption, RNA, Messenger, Exercise, Exercise Tolerance, Pulmonary Disease, Chronic Obstructive
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