Mitochondrial energetics is impaired in vivo in aged skeletal muscle
Open accessAbstract
Summary: With aging, most skeletal muscles undergo a progressive loss of mass and strength, a process termed sarcopenia. Aging‐related defects in mitochondrial energetics have been proposed to be causally involved in sarcopenia. However, changes in muscle mitochondrial oxidative phosphorylation with aging remain a highly controversial issue, creating a pressing need for integrative approaches to determine whether mitochondrial bioenergetics are impaired in aged skeletal muscle. To address this issue, mitochondrial bioenergetics was first investigated in vivo in the gastrocnemius muscle of adult (6 months) and aged (21 months) male W istar rats by combining a modular control analysis approach with 31 P magnetic resonance spectroscopy measurements of energetic metabolites. Using this innovative approach, we revealed that the in vivo responsiveness (‘elasticity’) of mitochondrial oxidative phosphorylation to contraction‐induced increase in ATP demand is significantly reduced in aged skeletal muscle, a reduction especially pronounced under low contractile activities. In line with this in vivo aging‐related defect in mitochondrial energetics, we found that the mitochondrial affinity for ADP is significantly decreased in mitochondria isolated from aged skeletal muscle. Collectively, the results of this study demonstrate that mitochondrial bioenergetics are effectively altered in vivo in aged skeletal muscle and provide a novel cellular basis for this phenomenon.
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Mechanisms for the reduction in systemic arteriovenous oxygen difference likely involve less efficient distribution of blood flow to exercising muscle and impaired mitochondrial function within the muscles.
“Mechanisms for the reduction in ∆AV˙o2 likely involve both less efficient distribution of blood flow to exercising muscle and impaired mitochondrial function within the muscles.13”
Changes in mitochondrial function alter the bioenergetic capacity of the heart, leading to diminished ability to meet energy demands with reduced ATP generation.
“Changes in mitochondrial function alter the bioenergetic capacity of the heart, leading to diminished ability to meet energy demands with reduced ATP generation.13,27”
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Cites
Sarcopenia: origins and clinical relevance
Rosenberg, I. H. (1997) · The Journal of Nutrition · doi:10.1093/jn/127.5.990s · Cited by 2,399 · see citing works
Visser, M., Goodpaster, B. H., Kritchevsky, S. B., Newman, A. B., Nevitt, M., Rubin, S. M., Simonsick, E. M., Harris, T. B., & Study, F. T. H. A. (2005) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/60.3.324 · Cited by 1,403 · see citing works
Decline in skeletal muscle mitochondrial function with aging in humans
Short, K. R., Bigelow, M. L., Kahl, J., Singh, R., Coenen-Schimke, J., Raghavakaimal, S., & Nair, K. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501559102 · Cited by 1,333 · see citing works
The AMP-activated protein kinase pathway – new players upstream and downstream
Hardie, D. G. (2004) · Journal of Cell Science · doi:10.1242/jcs.01540 · Cited by 1,136 · see citing works
Sarcopenia: origins and clinical relevance
Rosenberg, I. H. (2011) · Clinics in Geriatric Medicine · doi:10.1016/j.cger.2011.03.003 · Cited by 786 · see citing works
Oxidative capacity and ageing in human muscle
Conley, K. E., Jubrias, S. A., & Esselman, P. C. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00203.x · Cited by 651 · see citing works
Mitochondrial function and apoptotic susceptibility in aging skeletal muscle
Chabi, B., Ljubicic, V., Menzies, K. J., Huang, J. H., Saleem, A., & Hood, D. A. (2008) · Aging Cell · doi:10.1111/j.1474-9726.2007.00347.x · Cited by 437 · see citing works
Mitochondrial adenine nucleotide translocase is modified oxidatively during aging
Yan, L.-J., & Sohal, R. S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.12896 · Cited by 414 · see citing works
Drew, B., Phaneuf, S., Dirks, A. J., Selman, C., Gredilla, R., Lezza, A. M. S., Barja, G., & Leeuwenburgh, C. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00455.2002 · Cited by 287 · see citing works
Mitochondrial energy metabolism and ageing
Bratic, I., & Trifunović, A. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2010.01.004 · Cited by 268 · see citing works
Mammalian fuel utilization during sustained exercise
Brooks, G. A. (1998) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/s0305-0491(98)00025-x · Cited by 253 · see citing works
Picard, M., Ritchie, D., Wright, K. J., Romestaing, C., Thomas, M. M., Rowan, S. L., Taivassalo, T., & Hepple, R. T. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00628.x · Cited by 238 · see citing works
Skeletal muscle aging and the mitochondrion
Johnson, M. L., Robinson, M. M., & Nair, K. S. (2013) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2012.12.003 · Cited by 233 · see citing works
Mansouri, A., Muller, F. L., Liu, Y., Ng, R., Faulkner, J., Hamilton, M., Richardson, A., Huang, T.-T., Epstein, C. J., & Van Remmen, H. (2006) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2005.11.004 · Cited by 227 · see citing works
Skeletal muscle oxidative capacity in young and older women and men
Kent‐Braun, J. A., & Ng, A. V. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.3.1072 · Cited by 186 · see citing works
Marzetti, E., Wohlgemuth, S. E., Lees, H. A., Chung, H.-Y., Giovannini, S., & Leeuwenburgh, C. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.05.005 · Cited by 172 · see citing works
Mitochondrial DNA mutations, energy metabolism and apoptosis in aging muscle
Dirks, A. J., Hofer, T., Marzetti, E., Pahor, M., & Leeuwenburgh, C. (2006) · Ageing Research Reviews · doi:10.1016/j.arr.2006.03.002 · Cited by 169 · see citing works
Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans
Tonkonogi, M., Fernström, M., Walsh, B., Ji, L. L., Rooyackers, O., Hammarqvist, F., Wernerman, J., & Sahlin, K. (2003) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1044-9 · Cited by 159 · see citing works
Altered regional blood flow responses to submaximal exercise in older rats
Musch, T. I., Eklund, K. E., Hageman, K. S., & Poole, D. C. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00729.2003 · Cited by 140 · see citing works
Rasmussen, U. F., Krustrup, P., Kjær, M., & Rasmussen, H. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00092-5 · Cited by 132 · see citing works
Reduced mitochondrial coupling in vivo alters cellular energetics in aged mouse skeletal muscle
Marcinek, D. J., Schenkman, K. A., Ciesielski, W. A., Lee, D., & Conley, K. E. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.097782 · Cited by 123 · see citing works
Top Down Metabolic Control Analysis
Brand, M. D. (1996) · Journal of Theoretical Biology · doi:10.1006/jtbi.1996.0174 · Cited by 118 · see citing works
Lanza, I. R., Larsen, R. G., & Kent‐Braun, J. A. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.138362 · Cited by 111 · see citing works
Capel, F., Rimbert, V., Lioger, D., Diot, A., Rousset, P., Mirand, P. P., Boirie, Y., Morio, B., & Mosoni, L. (2005) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2004.11.001 · Cited by 108 · see citing works
Aging skeletal muscle mitochondria in the rat: decreased uncoupling protein-3 content
Kerner, J., Turkaly, P. J., Minkler, P. E., & Hoppel, C. L. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.5.e1054 · Cited by 106 · see citing works
Mitochondrial DNA alterations and reduced mitochondrial function in aging
Hebert, S. L., Lanza, I. R., & Nair, K. S. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2010.03.007 · Cited by 90 · see citing works
Lombardi, A., Silvestri, E., Cioffi, F., Senese, R., Lanni, A., Goglia, F., de Lange, P., & Moreno, M. (2009) · Journal of Proteomics · doi:10.1016/j.jprot.2009.02.007 · Cited by 82 · see citing works
Feng, J., Xie, H., Meany, D. L., Thompson, L. V., Arriaga, E. A., & Griffin, T. J. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.11.1137 · Cited by 78 · see citing works
Gouspillou, G., Bourdel-Marchasson, I., Rouland, R., Calmettes, G., Franconi, J.-M., Deschodt-Arsac, V., & Diolez, P. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.09.004 · Cited by 62 · see citing works
Self-citationChilibeck, P. D., McCreary, C. R., Marsh, G. D., Paterson, D. H., Noble, E. G., Taylor, A. W., & Thompson, R. T. (1998) · European Journal of Applied Physiology · doi:10.1007/s004210050446 · Cited by 56 · see citing works
Kumaran, S., Panneerselvam, K. S., Shila, S., Sivarajan, K., & Panneerselvam, C. (2005) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-005-8234-z · Cited by 49 · see citing works
Wray, D. W., Nishiyama, S. K., Monnet, A., Wary, C., Duteil, S., Carlier, P. G., & Richardson, R. S. (2009) · The Journals of Gerontology Series A · doi:10.1093/gerona/glp044 · Cited by 47 · see citing works
Hepple, R. T., & Vogell, J. E. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01309.2003 · Cited by 46 · see citing works
Does AMP-Activated Protein Kinase Negatively Mediate Aged Fast-Twitch Skeletal Muscle Mass?
Gordon, S. E., Lake, J. A., Westerkamp, C. M., & Thomson, D. M. (2008) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e3181877e13 · Cited by 41 · see citing works
Accurate Determination of the Oxidative Phosphorylation Affinity for ADP in Isolated Mitochondria
Gouspillou, G., Rouland, R., Calmettes, G., Deschodt‐Arsac, V., Franconi, J., Bourdel‐Marchasson, I., & Diolez, P. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020709 · Cited by 33 · see citing works
Self-citationSimplifying metabolic complexity
Martin, D. B., & Curtis, R. K. (2002) · Biochemical Society Transactions · doi:10.1042/bst0300025 · Cited by 29 · see citing works
Diolez, P., Deschodt‐Arsac, V., Raffard, G., Simon, C., Santos, P. D. D., Thiaudière, E., Arsac, L. M., & Franconi, J. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00189.2006 · Cited by 28 · see citing works
Self-citationCalmettes, G., Deschodt‐Arsac, V., Gouspillou, G., Miraux, S., Müller, B., Franconi, J., Thiaudière, E., & Diolez, P. (2010) · PLoS ONE · doi:10.1371/journal.pone.0009306 · Cited by 24 · see citing works
Self-citationMetabolite Changes in Aged Muscle During Stimulation
Dudley, G. A., & Fleck, S. J. (1984) · Journal of Gerontology · doi:10.1093/geronj/39.2.183 · Cited by 18 · see citing works
Decreased restitution of creatine phosphate in white and red skeletal muscles during aging
Ermini, M., & F.Verzár, F. (1968) · Cellular and Molecular Life Sciences · doi:10.1007/bf02138640 · Cited by 15 · see citing works
Phosphagens and glycogen content in skeletal muscle after treadmill training in young and old rats
Bastien, C., & S�nchez, J. (1984) · European Journal of Applied Physiology · doi:10.1007/bf01015212 · Cited by 14 · see citing works
In vivo modular control analysis of energy metabolism in contracting skeletal muscle
Arsac, L. M., Beuste, C., Miraux, S., Deschodt‐Arsac, V., Thiaudière, E., Franconi, J., & Diolez, P. (2008) · Biochemical Journal · doi:10.1042/bj20080280 · Cited by 11 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Exercise Promotes Healthy Aging of Skeletal Muscle
Cartee, G. D., Hepple, R. T., Bamman, M. M., & Zierath, J. R. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.007 · Cited by 483 · see citing works
Shields, H. J., Traa, A., & Van Raamsdonk, J. M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.628157 · Cited by 478 · see citing works
Mitochondrial quality control and muscle mass maintenance.
Romanello, V., & Sandri, M. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2015.00422 · Cited by 434 · see citing works
Forman, D. E., Arena, R., Boxer, R., Dolansky, M. A., Eng, J. J., Fleg, J. L., Haykowsky, M., Jahangir, A., Kaminsky, L. A., Kitzman, D. W., et al. (2017) · Circulation · doi:10.1161/cir.0000000000000483 · Cited by 319 · see citing works
Skeletal muscle aging: influence of oxidative stress and physical exercise
Gomes, M. J., Martinez, P. F., Pagan, L. U., Damatto, R. L., Mariano Cezar, M. D., Ruiz Lima, A. R., Okoshi, K., & Okoshi, M. P. (2017) · Oncotarget · doi:10.18632/oncotarget.14670 · Cited by 285 · see citing works
Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice
Leduc-Gaudet, J.-P., Picard, M., Pelletier, F. S.-J., Sgarioto, N., Auger, M.-J., Vallée, J., Robitaille, R., St-Pierre, D. H., & Gouspillou, G. (2015) · Oncotarget · doi:10.18632/oncotarget.4235 · Cited by 273 · see citing works
Self-citationAdvances in muscle health and nutrition: A toolkit for healthcare professionals
Prado, C. M., Landi, F., Chew, S. T. H., Atherton, P. J., Molinger, J., Ruck, T., & Gonzalez, M. C. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.07.041 · Cited by 237 · see citing works
Gouspillou, G., Sgarioto, N., Kapchinsky, S., Purves‐Smith, F., Norris, B., Pion, C. H., Barbat‐Artigas, S., Lemieux, F., Taivassalo, T., Morais, J. A., et al. (2014) · The FASEB Journal · doi:10.1096/fj.13-242750 · Cited by 217 · see citing works
Self-citationSt‐Jean‐Pelletier, F., Pion, C. H., Leduc‐Gaudet, J., Sgarioto, N., Zovilé, I., Barbat‐Artigas, S., Reynaud, O., Alkaterji, F., Lemieux, F. C., Grenon, A., et al. (2017) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12139 · Cited by 156 · see citing works
Self-citationPicca, A., Lezza, A. M. S., Leeuwenburgh, C., Pesce, V., Calvani, R., Bossola, M., Manes-Gravina, E., Landi, F., Bernabei, R., & Marzetti, E. (2018) · Rejuvenation Research · doi:10.1089/rej.2017.1989 · Cited by 144 · see citing works
Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy
Sakellariou, G. K., Pearson, T., Lightfoot, A. P., Nye, G. A., Wells, N., Giakoumaki, I. I., Vasilaki, A., Griffiths, R. D., Jackson, M. J., & McArdle, A. (2016) · Scientific Reports · doi:10.1038/srep33944 · Cited by 133 · see citing works
Parkin overexpression protects from ageing‐related loss of muscle mass and strength
Leduc‐Gaudet, J., Reynaud, O., Hussain, S. N., & Gouspillou, G. (2019) · The Journal of Physiology · doi:10.1113/jp277157 · Cited by 119 · see citing works
Self-citationProtective role of Parkin in skeletal muscle contractile and mitochondrial function
Gouspillou, G., Godin, R., Piquereau, J., Picard, M., Mofarrahi, M., Mathew, J., Purves‐Smith, F. M., Sgarioto, N., Hepple, R. T., Burelle, Y., et al. (2018) · The Journal of Physiology · doi:10.1113/jp275604 · Cited by 115 · see citing works
Self-citationSgarbi, G., Matarrese, P., Pinti, M., Lanzarini, C., Ascione, B., Gibellini, L., Dika, E., Patrizi, A., Tommasino, C., Capri, M., et al. (2014) · Aging · doi:10.18632/aging.100654 · Cited by 90 · see citing works
Faitg, J., Leduc-Gaudet, J.-P., Reynaud, O., Ferland, G., Gaudreau, P., & Gouspillou, G. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00420 · Cited by 72 · see citing works
“Eight-micron thick serial cross-sections were cut in a cryostat at −18°C and mounted on lysine coated slides (Superfrost) to determine fiber type and mitochondrial content as previously described (Gouspillou et al., 2014).”
BackgroundMethodInfluentialSelf-citationExercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension
Musci, R., Hamilton, K., & Linden, M. (2019) · Sports · doi:10.3390/sports7070170 · Cited by 73 · see citing works
Regulation of muscle and mitochondrial health by the mitochondrial fission protein Drp1 in aged mice
Dulac, M., Leduc‐Gaudet, J., Cefis, M., Ayoub, M., Reynaud, O., Shams, A., Moamer, A., Nery Ferreira, M. F., Hussain, S. N., & Gouspillou, G. (2021) · The Journal of Physiology · doi:10.1113/jp281752 · Cited by 51 · see citing works
Self-citationOrganotypic cultures as aging associated disease models
Sanchez, M. M., Bagdasarian, I. A., Darch, W., & Morgan, J. T. (2022) · Aging · doi:10.18632/aging.204361 · Cited by 12 · see citing works
Li, M., Chen, F., Wang, H., Wu, W., Zhang, X., Tian, C., Yu, H., Liu, R., Zhu, B., Zhang, B., et al. (2016) · PeerJ · doi:10.7717/peerj.2259 · Cited by 8 · see citing works
- Authors
- Gouspillou, G., Bourdel‐Marchasson, I., Rouland, R., Calmettes, G., Biran, M., Deschodt‐Arsac, V., Miraux, S., Thiaudiere, E., Pasdois, P., Detaille, D., Franconi, J., Babot, M., Trézéguet, V., Arsac, L., & Diolez, P.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Université de Bordeaux (FR)
- Résonance Magnétique des Systèmes Biologiques UMR 5536 CNRS ‐ Bordeaux Segalen University Bordeaux France
- INSERM U1045 – Cardio‐Thoracic Research Centre – and Rhythmology and Heart Modeling Institute (LIRYC) Bordeaux University Bordeaux France
- Corresponding author
- Gouspillou, Gilles
- ORCID
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2013-09-19
- Volume
- 13
- Issue
- 1
- Pages
- 39-48
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC4326861
- OpenAlex
- W2093524310
- Cited by
- 147
- References
- 42
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 18 · 2023: 12 · 2022: 6 · 2021: 13 · 2020: 15 · 2019: 11 · 2018: 6 · 2017: 13 · 2016: 14 · 2015: 15 · 2014: 7 · 2013: 2
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- McGill University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- mitochondrial bioenergetics, skeletal muscle aging, sarcopenia, mitochondrial oxidative phosphorylation, ATP demand, ADP affinity, gastrocnemius, 31P NMR, contractile activity, Wistar rats
- MeSH terms
- Adenosine Diphosphate, Adenosine Triphosphate, Aging, Animals, Energy Metabolism, Hydrogen-Ion Concentration, Male, Mitochondria, Muscle Contraction, Oxidation-Reduction, Oxidative Phosphorylation, Phosphates, Phosphocreatine, Rats, Wistar, Muscle, Skeletal, Adenine Nucleotide Translocator 1, Rats
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