Skeletal muscle mitochondrial energetics are associated with maximal aerobic capacity and walking speed in older adults
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BACKGROUND: Lower ambulatory performance with aging may be related to a reduced oxidative capacity within skeletal muscle. This study examined the associations between skeletal muscle mitochondrial capacity and efficiency with walking performance in a group of older adults. METHODS: Thirty-seven older adults (mean age 78 years; 21 men and 16 women) completed an aerobic capacity (VO2 peak) test and measurement of preferred walking speed over 400 m. Maximal coupled (State 3; St3) mitochondrial respiration was determined by high-resolution respirometry in saponin-permeabilized myofibers obtained from percutanous biopsies of vastus lateralis (n = 22). Maximal phosphorylation capacity (ATPmax) of vastus lateralis was determined in vivo by (31)P magnetic resonance spectroscopy (n = 30). Quadriceps contractile volume was determined by magnetic resonance imaging. Mitochondrial efficiency (max ATP production/max O2 consumption) was characterized using ATPmax per St3 respiration (ATPmax/St3). RESULTS: In vitro St3 respiration was significantly correlated with in vivo ATPmax (r (2) = .47, p = .004). Total oxidative capacity of the quadriceps (St3*quadriceps contractile volume) was a determinant of VO2 peak (r (2) = .33, p = .006). ATPmax (r (2) = .158, p = .03) and VO2 peak (r (2) = .475, p < .0001) were correlated with preferred walking speed. Inclusion of both ATPmax/St3 and VO2 peak in a multiple linear regression model improved the prediction of preferred walking speed (r (2) = .647, p < .0001), suggesting that mitochondrial efficiency is an important determinant for preferred walking speed. CONCLUSIONS: Lower mitochondrial capacity and efficiency were both associated with slower walking speed within a group of older participants with a wide range of function. In addition to aerobic capacity, lower mitochondrial capacity and efficiency likely play roles in slowing gait speed with age.
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Age-related skeletal muscle deficits contribute to reductions in cardiorespiratory fitness, exercise tolerance, and overall physical function.
“Collectively, these age-related skeletal muscle deficits contribute to reductions in cardiorespiratory fitness (peak oxygen uptake [Vo2 peak]), exercise tolerance, and overall physical function (9, 10).”
From Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age (2015) · cites this paper as [10]
Loss of mitochondrial energetics in sub-optimal aging contributes to slower walking speed, fatigability, multimorbidity, frailty and sarcopenia.
“recent studies have shown that loss of mitochondrial energetics in sub-optimal aging contributes to slower walking speed [[355], [356], [357], [358]], fatigability [359], multimorbidity [360], frailty [361] and sarcopenia [345,362].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [356]
Walking reduces the risk of dementia in a dose-dependent manner, with walking less than 0.25 miles per day compared to walking >2 miles per day, controlling for other risk factors.
“For instance, in a prospective cohort study, walking reduced the risk of dementia in a dose-dependent manner, with walking less than 0.25 miles per day compared to walking > 2 miles per day, controlling for other risk factors [356].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [356]
In a prospective cohort study, walking reduced risk of dementia in a dose-dependent manner, with walking less than 0.25 miles per day compared to walking >2 miles per day, controlling for other risk factors.
“For instance, in a prospective cohort study, walking reduced the risk of dementia in a dose-dependent manner, with walking less than 0.25 miles per day compared to walking > 2 miles per day, controlling for other risk factors [356].”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [356]
Evidence to date strongly implicates mitochondria as having a pivotal role in the pathogenesis of age-related functional decline, and reductions in autophagy appear to be a critical biological mechanism affecting the collective function of the mitochondrial pool.
“Thus, evidence to date strongly implicates the mitochondria as having a pivotal role in the pathogenesis of age-related functional decline,(Coen, Jubrias, Distefano, Amati, Mackey, Glynn, Manini, Wohlgemuth, Leeuwenburgh, Cummings, Newman, Ferrucci, Toledo, Shankland, Conley, and Goodpaster 2013) and reductions in autophagy appear to be a critical biological mechanism affecting the collective”
From Successful aging: Advancing the science of physical independence in older adults (2015) · cites this paper as Coen et al. 2013
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The Depressed Frail Phenotype: The Clinical Manifestation of Increased Biological Aging
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Combined Training Enhances Skeletal Muscle Mitochondrial Oxidative Capacity Independent of Age
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Self-citationMitochondria to motion: optimizing oxidative phosphorylation to improve exercise performance
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Targeting metabolism in cellular senescence, a role for intervention
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Optimizing Skeletal Muscle Anabolic Response to Resistance Training in Aging
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Biological Aging and the Future of Geriatric Psychiatry
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Regulation of Exercise-Induced Autophagy in Skeletal Muscle
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Platelet bioenergetics correlate with muscle energetics and are altered in older adults
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Self-citationWalking Exercise Therapy Effects on Lower Extremity Skeletal Muscle in Peripheral Artery Disease
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Mitochondrial and skeletal muscle health with advancing age
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Clinical Trials Targeting Aging
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- Authors
- Coen, P. M., Jubrias, S. A., Distefano, G., Amati, F., Mackey, D. C., Glynn, N. W., Manini, T. M., Wohlgemuth, S. E., Leeuwenburgh, C., Cummings, S. R., Newman, A. B., Ferrucci, L., Toledo, F. G. S., Shankland, E., Conley, K. E., & Goodpaster, B. H.
- Affiliations
- University of Pittsburgh (US)
- University of Washington Medical Center (US)
- California Pacific Medical Center (US)
- University of Florida (US)
- National Institute on Aging (US)
- ORCID
- Venue
- The Journals of Gerontology: Series A
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-09
- Volume
- 68
- Issue
- 4
- Pages
- 447-455
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC3593613
- OpenAlex
- W2115546051
- Cited by
- 323
- References
- 42
- Citations by year
- 2026: 19 · 2025: 19 · 2024: 40 · 2023: 30 · 2022: 20 · 2021: 43 · 2020: 26 · 2019: 20 · 2018: 14 · 2017: 19 · 2016: 34 · 2015: 16 · 2014: 14 · 2013: 8 · 2012: 1
- FWCI
- 30.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (acceptedVersion, other-oa)
- IRIS (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- University of Pittsburgh (P30-AG024827, UL1RR024153, RR024153)
- National Institutes of Health (UL1TR000005)
- National Institute on Aging (RC2AG036594, RC2AG036606, P30AG024827, P30AG028740)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR 41928, R01AR041928)
- National Center for Research Resources (RR-024153, UL1RR024153)
- National Center for Advancing Translational Sciences
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- skeletal muscle mitochondria, mitochondrial respiration, maximal aerobic capacity, peak oxygen uptake, walking speed, older adults, mitochondrial efficiency, oxidative capacity, vastus lateralis, aging
- MeSH terms
- Age Factors, Aged, Biopsy, Energy Metabolism, Postural Balance, Female, Humans, Male, Mitochondria, Muscle, Muscle Contraction, Oxygen Consumption, Physical Endurance, Physical Fitness, Walking, Muscle, Skeletal, Quadriceps Muscle
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