Aging impairs skeletal muscle mitochondrial bioenergetic function
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This study investigated the influence of age on the functional status of mitochondria isolated from skeletal muscle of C57BL/6 mice aged 3 and 18 months. We hypothesized that skeletal muscle mitochondria isolated from aged animals will exhibit a decreased respiratory function. Mitochondrial respiratory functional measures (ie, State 3 and 4 respiration, respiratory control ratio and number of nanomoles of ADP phosphorylated by nanomoles of O(2) consumed per mitochondrion) and biochemical markers of oxidative damage (aconitase activity, protein carbonyl derivatives, sulfhydryl groups, and malondialdehyde) were measured in isolated mitochondrial suspensions. Along with traditional tests of mitochondrial function, an in vitro repetitive ADP-stimulation test was used to evaluate the mitochondrial capacity to reestablish the homeostatic balance between successive ADP stimulations. The number of mitochondria per mitochondrial suspension, calculated by transmission electron microscopy, was used to normalize functional and biochemical data. Our results confirm the existence of an age-associated decline in mitochondrial function of mixed skeletal muscle, which is significantly correlated with higher levels of mitochondrial oxidative damage.
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There is substantial evidence of increased ROS production and oxidative stress-induced damage to mtDNA and ETC complexes in aged rodents and non-human primates, as well as in human vastus lateralis muscle.
“there is substantial evidence showing increased ROS production and associated oxidative stress-induced damage to mitochondrial DNA (mtDNA) and ETC complexes in aged rodents and non-human primates (Figueiredo, Powers, Ferreira, Appell, and Duarte 2009;Lee, Choi, Birkenfeld, Alves, Jornayvaz, Jurczak, Zhang, Woo, Shadel, and Ladiges 2010;Lee, Wang, and Fanburg 1998;WANAGAT, CAO, PATHARE, and AIKEN 2”
From Successful aging: Advancing the science of physical independence in older adults (2015) · cites this paper as Figueiredo et al. 2009
Cites
[30] Microsomal lipid peroxidation
Buege, J. A., & Aust, S. D. (1978) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(78)52032-6 · Cited by 13,437 · see citing works
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · see citing works
Mitochondrial free radical generation, oxidative stress, and aging
Cadenas, E., & Davies, K. J. A. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00317-8 · Cited by 3,010 · see citing works
Stadtman, E. R. (1992) · Science · doi:10.1126/science.1355616 · Cited by 2,701 · see citing works
What is the cause of the ageing atrophy?
Lexell, J. E., Taylor, C. C., & Sjöstróm, M. (1988) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(88)90132-3 · Cited by 2,080 · see citing works
Oxidative damage and mitochondrial decay in aging.
Shigenaga, M. K., Hagen, T. M., & Ames, B. N. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.23.10771 · Cited by 2,055 · see citing works
THE MITOCHONDRIAL DEATH/LIFE REGULATOR IN APOPTOSIS AND NECROSIS
Kroemer, G., Dallaporta, B., & Resche-Rigon, M. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.619 · Cited by 1,971 · see citing works
[7] Mitochondrial respiratory control and the polarographic measurement of ADP : O ratios
Estabrook, R. W. (1967) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(67)10010-4 · Cited by 1,782 · see citing works
Regulation of Contraction in Striated Muscle
Gordon, A. M., Homsher, E. E., & Regnier, M. (2000) · Physiological Reviews · doi:10.1152/physrev.2000.80.2.853 · Cited by 1,740 · 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
[41] Measurement of protein thiol groups and glutathione in plasma
Hu, M. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(94)33044-1 · Cited by 962 · see citing works
Exercise and Sport Sciences Reviews
Barnhill, J. E. (1986) · Military Medicine · doi:10.1093/milmed/151.6.a15a · Cited by 705 · see citing works
Oxidative damage during aging targets mitochondrial aconitase
Yan, L., Levine, R. L., & Sohal, R. S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11168 · Cited by 620 · see citing works
Duchen, M. R. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.001aa.x · Cited by 610 · see citing works
Aging of human muscle: structure, function and adaptability
Porter, M. M., Vandervoort, A. A., & Lexell, J. E. (1995) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.1995.tb00026.x · Cited by 555 · see citing works
Sohal, R. S. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00856-0 · Cited by 477 · 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
Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones
Coore, H. G., Denton, R. M., Martin, B. R., & Randle, P. J. (1971) · Biochemical Journal · doi:10.1042/bj1250115 · Cited by 395 · see citing works
Apoptosis in skeletal muscle with aging
Dirks, A., & Leeuwenburgh, C. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00458.2001 · Cited by 377 · see citing works
Paradies, G., Petrosillo, G., Pistolese, M., & Ruggiero, F. M. (2002) · Gene · doi:10.1016/s0378-1119(01)00814-9 · Cited by 372 · see citing works
The Relation of Muscle Biochemistry to Muscle Physiology
Eisenberg, E., & Greene, L. E. (1980) · Annual Review of Physiology · doi:10.1146/annurev.ph.42.030180.001453 · Cited by 296 · 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
López-Torres, M., Gredilla, R., Sanz, A., & Barja, G. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00773-6 · Cited by 277 · see citing works
Kwong, L. K., & Sohal, R. S. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1495 · Cited by 273 · see citing works
Glutathione contents of tissues in the aging mouse
Hazelton, G. A., & Lang, C. A. (1980) · Biochemical Journal · doi:10.1042/bj1880025 · Cited by 268 · see citing works
Aging Selectively Decreases Oxidative Capacity in Rat Heart Interfibrillar Mitochondria
Fannin, S. W., Lesnefsky, E. J., Slabe, T. J., Hassan, M. O., & Hoppel, C. L. (1999) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1508 · Cited by 262 · see citing works
Mitochondrial function and dysfunction in the cell: its relevance to aging and aging-related disease
Nicholls, D. G. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00077-8 · Cited by 246 · see citing works
Apoptosis and Aging: Role of the Mitochondria
Pollack, M., & Leeuwenburgh, C. (2001) · The Journals of Gerontology Series A · doi:10.1093/gerona/56.11.b475 · Cited by 241 · see citing works
Oxidative damage to mitochondria and aging
Remmen, H. V. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00093-6 · 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
Lipid peroxidation in aging and age-dependent diseases
Spiteller, G. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00131-0 · Cited by 218 · see citing works
Magalhães, J., Ascensão, A. A. M. R., Soares, J. M. C., Ferreira, R. M., Neuparth, M. J., Marques, F., & Duarte, J. A. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01324.2004 · Cited by 190 · see citing works
Self-citationTONKONOGI, M., & SAHLIN, K. (1997) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1997.00222.x · Cited by 184 · see citing works
Ion transport ATPases as targets for free radical damage
Rohn, T. T., Hinds, T. R., & Vincenzi, F. F. (1993) · Biochemical Pharmacology · doi:10.1016/0006-2952(93)90530-a · Cited by 176 · see citing works
Cytochromecrelease from mitochondria in the aging heart: a possible mechanism for apoptosis with age
Phaneuf, S., & Leeuwenburgh, C. (2002) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00296.2001 · Cited by 174 · see citing works
Tonkonogi, M., Walsh, B. J., Svensson, M., & Sahlin, K. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00379.x · Cited by 161 · 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
Principles of Animal Use for Gerontological Research
Miller, R. A., & Nadon, N. L. (2000) · The Journals of Gerontology Series A · doi:10.1093/gerona/55.3.b117 · Cited by 153 · see citing works
Wibom, R., Hagenfeldt, L., & von Döbeln, U. (2002) · Analytical Biochemistry · doi:10.1016/s0003-2697(02)00424-4 · Cited by 148 · see citing works
Stadtman, E. R. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00904-8 · Cited by 133 · 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
Mitochondrial Dysfunction in the Senescence Accelerated Mouse (SAM)
Nakahara, H., Kanno, T., Inai, Y., Utsumi, K., Hiramatsu, M., Mori, A., & Packer, L. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00164-0 · Cited by 120 · see citing works
Energetic Aspects of Skeletal Muscle Contraction
Rail, J. A. (1985) · Exercise and Sport Sciences Reviews · doi:10.1249/00003677-198500130-00004 · Cited by 112 · see citing works
Desai, V. G., Weindruch, R. H., Hart, R. W., & Feuers, R. J. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0375 · Cited by 109 · see citing works
The role of mitochondria in aging of skeletal muscle
Figueiredo, P. A., Mota, M. P., Appell, H. J., & Duarte, J. A. (2008) · Biogerontology · doi:10.1007/s10522-007-9121-7 · Cited by 109 · see citing works
Self-citationOxidative biochemical markers; clues to understanding aging in long-lived species
Floyd, R. A., West, M., & Hensley, K. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00231-x · Cited by 106 · 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
Mitochondria, aging and longevity – a new perspective
Salvioli, S., Bonafè, M., Capri, M., Monti, D., & Franceschi, C. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02199-8 · Cited by 100 · see citing works
Sugiyama, S., Takasawa, M., Hayakawa, M., & Ozawa, T. (1993) · PubMed · Cited by 99 · see citing works
Dependence of excitotoxic neurodegeneration on mitochondrial aconitase inactivation
Li, Q., Pedersen, C., Day, B. J., & Patel, M. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00457.x · Cited by 96 · see citing works
Barrientos, A., Casademont, J., Rötig, A., Miró, Ò., Urbano-Márquez, Á., Rustin, P., & Cardellach, F. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1839 · Cited by 95 · see citing works
Rasmussen, U. F., Krustrup, P., Kjær, M., & Rasmussen, H. (2003) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-003-1022-2 · Cited by 82 · see citing works
Figueiredo, P., Ferreira, R. M., Appell, H.-J., & Duarte, J. A. (2008) · The Journals of Gerontology Series A · doi:10.1093/gerona/63.4.350 · Cited by 65 · see citing works
Self-citationThe conversion of citrate into cis-aconitate and isocitrate in the presence of aconitase
Krebs, H. A., & Holzach, O. (1952) · Biochemical Journal · doi:10.1042/bj0520527 · Cited by 61 · see citing works
Beyer, R. E., Starnes, J. W., Edington, D. W., Lipton, R. J., Compton, R. T., & Kwasman, M. A. (1984) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(84)90116-7 · Cited by 51 · see citing works
Regulation of Skeletal Muscle Mitochondrial Content During Aging
Lyons, C. N., Mathieu-Costello, O. A., & Moyes, C. D. (2006) · The Journals of Gerontology Series A · doi:10.1093/gerona/61.1.3 · Cited by 43 · see citing works
Ansved, T., & Edström, L. (1991) · Europe PMC (PubMed Central) · Cited by 36 · see citing works
Faist, V., Koenig, J., Hoeger, H., et al. (1998) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240050764 · Cited by 25 · see citing works
Effect of contractile activity on protein turnover in skeletal muscle mitochondrial subfractions
Connor, M. K., Si, B., Escobar, C., & Hood, D. A. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.5.1601 · Cited by 25 · see citing works
Figueiredo, P., Mota, M. P., Appell, H.-J., & Duarte, J. A. (2006) · European Review of Aging and Physical Activity · doi:10.1007/s11556-006-0011-9 · Cited by 15 · see citing works
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Price, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.003 · Cited by 1,602 · see citing works
Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials
Marzetti, E., Calvani, R., Cesari, M., Buford, T. W., Lorenzi, M., Behnke, B. J., & Leeuwenburgh, C. (2013) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2013.06.024 · Cited by 627 · see citing works
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Successful aging: Advancing the science of physical independence in older adults
Anton, S. D., Woods, A. J., Ashizawa, T., Barb, D., Buford, T. W., Carter, C. S., Clark, D. J., Cohen, R. A., Corbett, D. B., Cruz-Almeida, Y., et al. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.09.005 · Cited by 292 · see citing works
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Koltai, E., Szabo, Z., Atalay, M., Boldogh, I., Naito, H., Goto, S., Nyakas, C., & Radak, Z. (2010) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2009.11.002 · Cited by 283 · see citing works
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Pugh, T. D., Conklin, M. W., Evans, T. D., Polewski, M. A., Barbian, H. J., Pass, R., Anderson, B. D., Colman, R. J., Eliceiri, K. W., Keely, P. J., et al. (2013) · Aging Cell · doi:10.1111/acel.12091 · Cited by 81 · see citing works
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- Authors
- Figueiredo, P. A., Powers, S. K., Ferreira, R. M., Appell, H. J., & Duarte, J. A.
- Affiliations
- Universidade do Porto (PT)
- University of Florida (US)
- German Sport University Cologne (DE)
- Venue
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-01-01
- Volume
- 64A
- Issue
- 1
- Pages
- 21-33
- ISSN
- 1079-5006 (ISSN-L)
- 1758-535X
- PMC
- PMC2691197
- OpenAlex
- W2144365152
- Cited by
- 102
- References
- 60
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 8 · 2014: 7 · 2013: 10 · 2012: 7
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journals of Gerontology Series A (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- 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
- aging, skeletal muscle, mitochondrial function, mitochondrial bioenergetics, oxidative damage, respiratory control ratio, ADP phosphorylation, aconitase activity, protein carbonylation, malondialdehyde, sulfhydryl groups, mitochondrial homeostasis, C57BL/6 mice
- MeSH terms
- Aging, Animals, Citrate (si)-Synthase, Electrophoresis, Polyacrylamide Gel, Energy Metabolism, Male, Mice, Inbred C57BL, Mitochondria, Muscle, Muscle Proteins, Lipid Peroxidation, Oxidative Stress, Muscle, Skeletal, Cytochromes c, Microscopy, Electron, Transmission, Mice
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