Oxidative stress and mitochondrial impairment can be separated from lipofuscin accumulation in aged human skeletal muscle
Abstract
Summary: According to the free radical theory of aging, reactive oxygen species (ROS) act as a driving force of the aging process, and it is generally believed that mitochondrial dysfunction is a major source of increased oxidative stress in tissues with high content of mitochondria, such as muscle or brain. However, recent experiments in mouse models of premature aging have questioned the role of mitochondrial ROS production in premature aging. To address the role of mitochondrial impairment and ROS production for aging in human muscles, we have analyzed mitochondrial properties in muscle fibres isolated from the vastus lateralis of young and elderly donors. Mitochondrial respiratory functions were addressed by high‐resolution respirometry, and ROS production was analyzed by in situ staining with the redox‐sensitive dye dihydroethidium. We found that aged human skeletal muscles contain fully functional mitochondria and that the level of ROS production is higher in young compared to aged muscle. Accordingly, we could not find any increase in oxidative modification of proteins in muscle from elderly donors. However, the accumulation of lipofuscin was identified as a robust marker of human muscle aging. The data support a model, where ROS‐induced molecular damage is continuously removed, preventing the accumulation of dysfunctional mitochondria despite ongoing ROS production.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Most studies of mitochondrial respiration have not considered important covariates such as participant physical activity levels, adiposity, and fiber type percentage, which could confound the relationship between mitochondrial capacity and age.
“Moreover, most studies of mitochondrial respiration have not considered important covariates such as participant physical activity levels (9), adiposity (11), and fiber type percentage, which could confound the relationship between mitochondrial capacity and age (10,12,18,19).”
From Chronological Age Does not Influence<i>Ex-vivo</i>Mitochondrial Respiration and Quality Control in Skeletal Muscle (2016) · cites this paper as [12]
Several studies found no effect of age on mitochondrial oxidative capacity.
“several studies found no effect of age on mitochondrial oxidative capacity [[345], [346], [347], [348], [349]]”
From Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR) (2025) · cites this paper as [346]
Accumulation of lipofuscin particles in aged muscles from rodents and humans suggests that autophagy-lysosomal function is defective.
“several studies have observed an accumulation of lipofuscin particles in aged muscles from rodents [47] and humans [111,112], suggesting that the autophagy-lysosomal function is defective.”
From Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging (2021) · cites this paper as [111]
These changes were not accompanied by increased levels of oxidative stress, a finding that has also been confirmed in humans.
“Interestingly, these changes were not accompanied by increased levels of oxidative stress, a finding that has also been confirmed in humans (Hutter et al., 2007).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Hutter et al., 2007
Cites
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567 · see citing works
Mitochondria, Oxidants, and Aging
Balaban, R. S., Nemoto, S., & Finkel, T. (2005) · Cell · doi:10.1016/j.cell.2005.02.001 · Cited by 4,388 · 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
Premature ageing in mice expressing defective mitochondrial DNA polymerase
Trifunovic, A., Wredenberg, A., Falkenberg, M., Spelbrink, J. N., Rovio, A. T., Bruder, C. E., Bohlooly-Y, M., Gidlöf, S., Oldfors, A., Wibom, R., et al. (2004) · Nature · doi:10.1038/nature02517 · Cited by 2,734 · see citing works
Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging
Kujoth, G. C., Hiona, A., Pugh, T. D., Someya, S., Panzer, K., Wohlgemuth, S. E., Hofer, T., Seo, A. Y., Sullivan, R., Jobling, W. A., et al. (2005) · Science · doi:10.1126/science.1112125 · Cited by 2,165 · see citing works
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107 · see citing works
Extension of murine life span by overexpression of catalase targeted to mitochondria
Schriner, S. E., Linford, N. J., Martin, G. M., Treuting, P., Ogburn, C. E., Emond, M., Coskun, P. E., Ladiges, W., Wolf, N., Van Remmen, H., et al. (2005) · Science · doi:10.1126/science.1106653 · Cited by 1,724 · 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
Age-related changes in oxidized proteins.
Oliver, C. N., Ahn, B. W., Moerman, E. J., Goldstein, S., & Stadtman, E. R. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45598-6 · Cited by 1,306 · see citing works
Brunk, U. T., & Terman, A. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00959-0 · Cited by 919 · see citing works
Mitochondrial threshold effects
Rossignol, R., Faustin, B., Rocher, C., Malgat, M., Mazat, J., & Letellier, T. (2003) · Biochemical Journal · doi:10.1042/bj20021594 · Cited by 802 · see citing works
Does oxidative damage to DNA increase with age?
Hamilton, M. L., Van Remmen, H., Drake, J. A., Yang, H., Guo, Z. M., Kewitt, K., Walter, C. A., & Richardson, A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.171202698 · Cited by 768 · see citing works
The mitochondrial‐lysosomal axis theory of aging
Brunk, U. T., & Terman, A. (2002) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2002.02869.x · Cited by 729 · see citing works
Intracellular hydrogen peroxide and superoxide anion detection in endothelial cells
Carter, W. O., Naryanan, P. K., & Robinson, J. P. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.55.2.253 · Cited by 636 · see citing works
Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production
Trifunovic, A., Hansson, A., Wredenberg, A., Rovio, A. T., Dufour, E., Khvorostov, I., Spelbrink, J. N., Wibom, R., Jacobs, H. T., & Larsson, N.-G. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508886102 · Cited by 555 · see citing works
Maillard reaction products in tissue proteins: New products and new perspectives
Thorpe, S. R., & Baynes, J. (2003) · Amino Acids · doi:10.1007/s00726-003-0017-9 · Cited by 543 · see citing works
Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle
Boushel, R., Gnaiger, E., Schjerling, P., Skovbro, M., Kraunsøe, R., & Dela, F. (2007) · Diabetologia · doi:10.1007/s00125-007-0594-3 · Cited by 519 · see citing works
Self-citationOxidative modification of proteins during aging
Levine, R. L., & Stadtman, E. R. (2001) · Experimental Gerontology · doi:10.1016/s0531-5565(01)00135-8 · Cited by 466 · see citing works
Dröge, W. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-8997-0_14 · Cited by 415 · see citing works
Oxidative Stress, Accumulation of Biological 'Garbage', and Aging
Terman, A., & Brunk, U. T. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.197 · Cited by 363 · see citing works
Pérez‐Campo, R., Lopez‐Torres, M., Cadenas, S., Rojas, C., & Barja, G. (1998) · Journal of Comparative Physiology B · doi:10.1007/s003600050131 · Cited by 356 · see citing works
Oxidative damage to mitochondrial DNA and its relationship to ageing
Richter, C. (1995) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/1357-2725(95)00025-k · Cited by 351 · see citing works
Judge, S., Jang, Y. M., SMITH, A. R. W., Hagen, T. M., & Leeuwenburgh, C. (2005) · The FASEB Journal · doi:10.1096/fj.04-2622fje · Cited by 328 · see citing works
Ploug, T., van Deurs, B., Ai, H., Cushman, S. W., & Ralston, E. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.142.6.1429 · Cited by 302 · see citing works
Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts
Hayakawa, M., Hattori, K., Sugiyama, S., & Ozawa, T. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)92300-m · Cited by 283 · see citing works
Fink, B., Laude, K. M., McCann, L. A., Doughan, A. K., Harrison, D. G., & Dikalov, S. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00028.2004 · Cited by 259 · see citing works
Barja, G. (2004) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1017/s1464793103006213 · Cited by 232 · see citing works
Loeb, L. A., Wallace, D. C., & Martin, G. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509776102 · Cited by 226 · see citing works
Age-associated accumulation of 8-hydroxydeoxyguanosine in mitochondrial DNA of human diaphragm
Hayakawa, M., Torii, K., Sugiyama, S., Tanaka, M., & Ozawa, T. (1991) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(91)91921-x · Cited by 199 · see citing works
Khrapko, K., Bodyak, N. D., Thilly, W. G., van Orsouw, N. J., Zhang, X., Coller, H. A., Perls, T. T., Upton, M. P., Vijg, J., & Wei, J. Y. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.11.2434 · Cited by 179 · see citing works
Kuznetsov, A. V., Schneeberger, S., Seiler, R., Brandacher, G., Mark, W., Steurer, W., Saks, V. A., Usson, Y., Margreiter, R., & Gnaiger, E. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00701.2003 · Cited by 168 · see citing works
Elimination of damaged proteins during differentiation of embryonic stem cells
Hernebring, M., Brolén, G., Aguilaniu, H., Semb, H., & Nyström, T. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510944103 · Cited by 146 · see citing works
Oxygen Conformance of Cellular Respiration
Gnaiger, E. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-8997-0_4 · Cited by 143 · 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
Renner, K., Amberger, A., Konwalinka, G., Kofler, R., & Gnaiger, E. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(03)00105-8 · Cited by 123 · see citing works
High-resolution respirometry–a modern tool in aging research
Hütter, E., Unterluggauer, H., Garedew, A., Jansen‐Dürr, P., & Gnaiger, E. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.09.011 · Cited by 121 · see citing works
Self-citationThe mitochondrial theory of aging: dead or alive?
Jacobs, H. T. (2003) · Aging Cell · doi:10.1046/j.1474-9728.2003.00032.x · Cited by 117 · see citing works
Myocyte aging and mitochondrial turnover
Terman, A., & Brunk, U. T. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.01.005 · Cited by 100 · see citing works
Stöckl, P., Hütter, E., Zwerschke, W., & Jansen-Dürr, P. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.04.009 · Cited by 99 · see citing works
Self-citationResistance training and insulin action in humans: effects of de-training
Andersen, J. L., Schjerling, P., Andersen, L. L., & Dela, F. (2003) · The Journal of Physiology · doi:10.1111/j.1469-7793.2003.01049.x · Cited by 86 · see citing works
Self-citationMitochondrial DNA deletion mutations and sarcopenia
AIKEN, J., BUA, E., CAO, Z., LOPEZ, M., WANAGAT, J., McKENZIE, D., & McKIERNAN, S. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02111.x · Cited by 85 · 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
Age-related changes in the skeletal muscle cells.
Beregi, E., Regius, O., Hüttl, T. P., & Göbl, Z. (1988) · PubMed · Cited by 81 · see citing works
Mechanisms of sarcopenia of aging.
Short, K. R., & Nair, K. S. (1999) · PubMed · Cited by 79 · see citing works
Cottrell, D. A., & Turnbull, D. M. (2000) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200011000-00009 · Cited by 63 · see citing works
The Mitochondrial Theory of Aging
Kowald, A. (2001) · Neurosignals · doi:10.1159/000046885 · Cited by 62 · see citing works
Cadet, J., Berger, M., Morin, B., Raoul, S., & Wagner, J. R. (1995) · Birkhäuser Basel eBooks · doi:10.1007/978-3-0348-9074-8_5 · Cited by 60 · see citing works
Distribution of satellite cells in the human vastus lateralis muscle during aging
Renault, V., Rolland, E., Thornell, L.-E., Mouly, V., & Butler-Browne, G. (2002) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00095-5 · Cited by 56 · see citing works
Frenzei, H., & Feimann, J. (1984) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(84)90080-0 · Cited by 51 · see citing works
Rasmussen, U. F., Krustrup, P., Bangsbo, J., & Rasmussen, H. (2001) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s004240100689 · Cited by 41 · see citing works
Miller, R. A. (2005) · Science · doi:10.1126/science.310.5747.441 · Cited by 28 · see citing works
Tolar, M. (1980) · PubMed · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Newsholme, P., Haber, E. P., Hirabara, S. M., Rebelato, E. L. O., Procopio, J., Morgan, D., Oliveira‐Emilio, H. C., Carpinelli, A. R., & Curi, R. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.135871 · Cited by 684 · see citing works
New insights into the role of mitochondria in aging: mitochondrial dynamics and more
Seo, A. Y., Joseph, A.-M., Dutta, D., Hwang, J. C. Y., Aris, J. P., & Leeuwenburgh, C. (2010) · Journal of Cell Science · doi:10.1242/jcs.070490 · Cited by 522 · see citing works
Effects of Exercise and Aging on Skeletal MusclePreprint
Distéfano, G., & Goodpaster, B. H. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029785 · Cited by 493 · see citing works
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
Capacity of oxidative phosphorylation in human skeletal muscle
Gnaiger, E. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.03.013 · Cited by 446 · see citing works
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., et al. (2013) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gls196 · Cited by 323 · see citing works
Skeletal Muscle Mitochondria and Aging: A Review
Peterson, C. M., Johannsen, D. L., & Ravussin, É. (2012) · Journal of Aging Research · doi:10.1155/2012/194821 · Cited by 318 · see citing works
Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology
Settembre, C., & Perera, R. M. (2023) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-023-00676-x · Cited by 296 · see citing works
Barja, G. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5148 · Cited by 290 · see citing works
Izquierdo, M., de Souto Barreto, P., Arai, H., Bischoff-Ferrari, H. A., Cadore, E. L., Cesari, M., Chen, L.-K., Coen, P. M., Courneya, K. S., Duque, G., et al. (2025) · The Journal of nutrition, health and aging · doi:10.1016/j.jnha.2024.100401 · Cited by 273 · see citing works
Mitochondrial Dynamics and Mitophagy in Skeletal Muscle Health and Aging
Leduc-Gaudet, J.-P., Hussain, S. N. A., Barreiro, E., & Gouspillou, G. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158179 · Cited by 268 · see citing works
“In line with this view, several studies have observed an accumulation of lipofuscin particles in aged muscles from rodents [47] and humans [111,112], suggesting that the autophagy-lysosomal function is defective.”
ResultHIONA, A. (2008) · Experimental Gerontology · doi:10.1016/j.exger.2007.10.001 · Cited by 247 · 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
Mechanisms of skeletal muscle aging: insights from <i>Drosophila</i> and mammalian models
Demontis, F., Piccirillo, R., Goldberg, A. L., & Perrimon, N. (2013) · Disease Models & Mechanisms · doi:10.1242/dmm.012559 · 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
Lanza, I. R., Zabielski, P., Klaus, K. A., Morse, D. M., Heppelmann, C. J., Bergen, H. R., Dasari, S., Walrand, S., Short, K. R., Johnson, M. L., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.11.003 · Cited by 227 · 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
Mitochondria, Muscle Health, and Exercise with Advancing Age
Carter, H. N., Chen, C. C. W., & Hood, D. A. (2015) · Physiology · doi:10.1152/physiol.00039.2014 · Cited by 191 · see citing works
Joseph, A., Adhihetty, P. J., & Leeuwenburgh, C. (2016) · The Journal of Physiology · doi:10.1113/jp270659 · Cited by 186 · see citing works
Skeletal muscle autophagy and its role in sarcopenia and organismal aging
Jiao, J., & Demontis, F. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.03.009 · Cited by 184 · see citing works
Angulo, J., Assar, M. E., & Rodríguez‐Mañas, L. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.06.001 · Cited by 185 · see citing works
Distéfano, G., Standley, R. A., Zhang, X., Carnero, E. Á., Yi, F., Cornnell, H. H., & Coen, P. M. (2018) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12272 · Cited by 176 · see citing works
Skeletal Muscle Mitochondria in the Elderly: Effects of Physical Fitness and Exercise Training
Broskey, N. T., Greggio, C., Boss, A., Boutant, M., Dwyer, A., Schlueter, L., Hans, D., Gremion, G., Kreis, R., Boesch, C., et al. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3983 · Cited by 157 · see citing works
Mitochondria as a Target for Mitigating Sarcopenia
Coen, P. M., Musci, R., Hinkley, J., & Miller, B. F. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2018.01883 · Cited by 140 · see citing works
Mitochondrial Involvement and Impact in Aging Skeletal Muscle
Hepple, R. T. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00211 · Cited by 155 · see citing works
Picard, M. A., Ritchie, D., Thomas, M. M., Wright, K. J., & Hepple, R. T. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00745.x · Cited by 145 · see citing works
Mitochondrial respiratory capacity and coupling control decline with age in human skeletal muscle
Porter, C., Hurren, N. M., Cotter, M. V., Bhattarai, N., Reidy, P. T., Dillon, E. L., Durham, W. J., Tuvdendorj, D., Sheffield-Moore, M., Volpi, E., et al. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00125.2015 · Cited by 134 · see citing works
Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4
Kozieł, R., Pircher, H., Kratochwil, M., Lener, B., Hermann, M., Dencher, N. A., & Jansen‐Dürr, P. (2013) · Biochemical Journal · doi:10.1042/bj20121778 · Cited by 135 · see citing works
Self-citationMechanism of Oxidative DNA Damage in Diabetes
Simone, S., Gorin, Y. C., Velagapudi, C., Abboud, H. E., & Habib, S. L. (2008) · Diabetes · doi:10.2337/db07-1579 · Cited by 129 · see citing works
Evidence of mitochondrial dysfunction and impaired ROS detoxifying machinery in Fanconi Anemia cells
Kumari, U., Jun, W. Y., Bay, B., & Lyakhovich, A. (2013) · Oncogene · doi:10.1038/onc.2012.583 · Cited by 123 · see citing works
Relationship between Human Aging Muscle and Oxidative System Pathway
Doria, E., Buonocore, D., Focarelli, A., & Marzatico, F. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/830257 · Cited by 117 · see citing works
Update on mitochondria and muscle aging: All wrong roads lead to sarcopenia
Picca, A., Calvani, R., Bossola, M., Allocca, E., Menghi, A., Pesce, V., Lezza, A. M. S., Bernabei, R., Landi, F., & Marzetti, E. (2018) · Biological Chemistry · doi:10.1515/hsz-2017-0331 · Cited by 116 · see citing works
Granic, A., Suetterlin, K., Shavlakadze, T., Grounds, M. D., & Sayer, A. A. (2023) · Clinical Science · doi:10.1042/cs20230319 · Cited by 118 · see citing works
Sex differences in mitochondrial respiratory function in human skeletal muscle
Miotto, P. M., McGlory, C., Holloway, T. M., Phillips, S. M., & Holloway, G. P. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00025.2018 · Cited by 109 · see citing works
Lipofuscin: Detection and Quantification by Microscopic Techniques
Jung, T., Höhn, A., & Grune, T. (2009) · Methods in molecular biology · doi:10.1007/978-1-60761-411-1_13 · Cited by 108 · see citing works
Lanza, I. R., Bhagra, S., Nair, K. S., & Port, J. D. (2011) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.22733 · Cited by 103 · see citing works
β-cell autophagy: Mechanism and role in β-cell dysfunction
Lee, Y., Kim, J., Park, K., & Lee, M. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.014 · Cited by 102 · see citing works
Oxidative stress-a key emerging impact factor in health, ageing, lifestyle and aesthetics
Kandola, K., Bowman, A., & Birch‐Machin, M. A. (2015) · International Journal of Cosmetic Science · doi:10.1111/ics.12287 · Cited by 103 · see citing works
Denervation drives mitochondrial dysfunction in skeletal muscle of octogenarians
Spendiff, S., Vuda, M., Gouspillou, G., Aare, S., Pérez, A., Morais, J. A., Jagoe, R. T., Filion, M., Glicksman, R., Kapchinsky, S., et al. (2016) · The Journal of Physiology · doi:10.1113/jp272487 · Cited by 100 · see citing works
Mitochondria and Aging—The Role of Exercise as a Countermeasure
Nilsson, M. I., & Tarnopolsky, M. A. (2019) · Biology · doi:10.3390/biology8020040 · Cited by 92 · see citing works
Mitochondria and Diabetes. An Intriguing Pathogenetic Role
Newsholme, P., Gaudel, C., & Krause, M. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2869-1_10 · Cited by 90 · 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
Gram, M., Vigelsø, A., Yokota, T., Helge, J. W., Dela, F., & Hey‐Mogensen, M. (2015) · The Journal of Physiology · doi:10.1113/jp270211 · Cited by 86 · see citing works
Self-citationRegulation of skeletal muscle mitochondrial function: genes to proteins
Lanza, I. R., & Sreekumaran Nair, K. (2010) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02124.x · Cited by 83 · see citing works
Age-related differences in oxidative protein-damage in young and senescent fibroblasts
Jung, T., Höhn, A., Catalgol, B., & Grune, T. (2008) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2008.12.007 · Cited by 81 · see citing works
The Pleiotropic Effect of Physical Exercise on Mitochondrial Dynamics in Aging Skeletal Muscle
Barbieri, E., Agostini, D., Polidori, E., Potenza, L., Guescini, M., Lucertini, F., Annibalini, G., Stocchi, L., Santi, M. D., & Stocchi, V. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/917085 · Cited by 79 · see citing works
Distefano, G., Standley, R. A., Dubé, J. J., Carnero, E. A., Ritov, V. B., Stefanovic-Racic, M., Toledo, F. G. S., Piva, S. R., Goodpaster, B. H., & Coen, P. M. (2016) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/glw102 · Cited by 76 · see citing works
Gram, M., Vigelsø, A., Yokota, T., HANSEN, C. N., Helge, J. W., Hey‐Mogensen, M., & Dela, F. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.08.013 · Cited by 77 · see citing works
Self-citationTriolo, M., Oliveira, A. N., Kumari, R., & Hood, D. A. (2022) · Skeletal Muscle · doi:10.1186/s13395-022-00296-7 · Cited by 75 · see citing works
“For example, in muscle from aged rodents and humans, the presence of non-digestible lysosomal content, termed lipofuscin, is apparent [23, 57].”
BackgroundFeeney, E. J., Austin, S. L., Chien, Y., Mandel, H., Schoser, B. G. H., Prater, S. N., Hwu, W., Ralston, E., Kishnani, P. S., & Raben, N. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-2 · Cited by 71 · see citing works
Age-related Attenuation of Isoflurane Preconditioning in Human Atrial Cardiomyocytes
Mio, Y., Bienengraeber, M. W., Marinović, J., Gutterman, D. D., Rakić, M., Bosnjak, Z. J., & Stadnicka, A. (2008) · Anesthesiology · doi:10.1097/aln.0b013e318167af2d · Cited by 71 · see citing works
Impact of aging on mitochondrial function in cardiac and skeletal muscle
Hepple, R. T. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.03.017 · Cited by 68 · see citing works
Johnson, M. L., Lalia, A. Z., Dasari, S., Pallauf, M., Fitch, M., Hellerstein, M. K., & Lanza, I. R. (2015) · Aging Cell · doi:10.1111/acel.12352 · Cited by 66 · see citing works
Brzeszczyńska, J., Meyer, A. S., McGregor, R. A., Schilb, A., Degen, S., Tadini, V., Johns, N., LANGEN, R. C. J., Schols, A. M. W. J., Glass, D. J., et al. (2017) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.12252 · Cited by 65 · see citing works
Functional Interplay between Mitochondrial and Proteasome Activity in Skin Aging
Kozieł, R., Greussing, R., Maier, A. B., Declercq, L., & Jansen‐Dürr, P. (2010) · Journal of Investigative Dermatology · doi:10.1038/jid.2010.383 · Cited by 65 · see citing works
Self-citationHuang, J. H., & Hood, D. A. (2009) · IUBMB Life · doi:10.1002/iub.164 · Cited by 66 · see citing works
The influence of age and aerobic fitness: effects on mitochondrial respiration in skeletal muscle
Larsen, S., Hey‐Mogensen, M., Rabøl, R., Stride, N., Helge, J. W., & Dela, F. (2012) · Acta Physiologica · doi:10.1111/j.1748-1716.2012.02408.x · Cited by 63 · see citing works
Self-citationRole of autophagy in muscle disease
Franco‐Romero, A., & Sandri, M. (2021) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2021.101041 · Cited by 61 · see citing works
Manifestations of Age on Autophagy, Mitophagy and Lysosomes in Skeletal Muscle
Triolo, M., & Hood, D. A. (2021) · Cells · doi:10.3390/cells10051054 · Cited by 57 · see citing works
Targeting organ-specific mitochondrial dysfunction to improve biological aging
Madreiter‐Sokolowski, C. T., Hiden, U., Krstić, J., Panzitt, K., Wagner, M., Enzinger, C., Khalil, M., Abdellatif, M., Malle, E., Madl, T., et al. (2024) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2024.108710 · Cited by 54 · see citing works
Ralston, E., Swaim, B., Czapiga, M., Hwu, W., Chien, Y., Pittis, M. G., Bembi, B., Schwartz, O., Plötz, P. H., & Raben, N. (2008) · Journal of Structural Biology · doi:10.1016/j.jsb.2008.03.010 · Cited by 51 · see citing works
Altered mitochondrial regulation in quadriceps muscles of patients with COPD
Naimi, A. I., Bourbeau, J., Perrault, H., Baril, J., Wright‐Paradis, C., Rossi, A. M., Taivassalo, T., Sheel, A. W., Rabøl, R., Dela, F., et al. (2010) · Clinical Physiology and Functional Imaging · doi:10.1111/j.1475-097x.2010.00988.x · Cited by 51 · see citing works
Self-citationNyberg, M., Mortensen, S. P., Cabo, H., Gómez‐Cabrera, M. C., Viña, J., & Hellsten, Y. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.05.008 · Cited by 50 · see citing works
Strifler, G., Tuboly, E., Szél, E., Kaszonyi, E., Cao, C., Kaszaki, J., Mészáros, A., Boros, M., & Hartmann, P. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146363 · Cited by 46 · see citing works
Muscle aging and sarcopenia: The pathology, etiology, and most promising therapeutic targets
Grima-Terrén, M., Campanario, S., Ramírez‐Pardo, I., Cisneros, A., Hong, X., Perdiguero, E., Serrano, A. L., Isern, J., & Muñoz‐Cánoves, P. (2024) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2024.101319 · Cited by 49 · see citing works
Skeletal muscle as an experimental model of choice to study tissue aging and rejuvenation
Etienne, J., Liu, C., Skinner, C. M., Conboy, M. J., & Conboy, I. (2020) · Skeletal Muscle · doi:10.1186/s13395-020-0222-1 · Cited by 43 · see citing works
Blier, P. U., Abele, D., Munro, D., Dégletagne, C., Rodríguez, E., & Hagen, T. M. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.07.046 · Cited by 41 · see citing works
Miura, S., Saitoh, S., Kokubun, T., Owada, T., Yamauchi, H., Machii, H., & Takeishi, Y. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091897 · Cited by 41 · see citing works
de Oliveira, N. R. C., Marques, S. D. O., Luciano, T. F., Pauli, J. R., de Moura, L. P., Caperuto, É. C., Pieri, B. L. D. S., Engelmann, J., Scaini, G., STRECK, E. L., et al. (2014) · Mediators of Inflammation · doi:10.1155/2014/987017 · Cited by 39 · see citing works
RetractedFitzgerald, L. F., Christie, A. D., & Kent, J. A. (2016) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2016-0195 · Cited by 39 · see citing works
Mitochondria as Nutritional Targets to Maintain Muscle Health and Physical Function During Ageing
Broome, S. C., Whitfield, J., Karagounis, L. G., & Hawley, J. A. (2024) · Sports Medicine · doi:10.1007/s40279-024-02072-7 · Cited by 39 · see citing works
Layec, G., Gifford, J. R., Trinity, J. D., Hart, C. R., Garten, R. S., Park, S., Fur, Y. L., Jeong, E. K., & Richardson, R. S. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00028.2016 · Cited by 34 · see citing works
Sonjak, V., Jacob, K. J., Spendiff, S., Vuda, M., Pérez, A., Míguez, K., Minozzo, F. C., Spake, C. S. L., Morais, J. A., & Hepple, R. T. (2019) · The Journals of Gerontology Series A · doi:10.1093/gerona/glz066 · Cited by 34 · see citing works
Mitochondrial Dysfunction in Aging and Longevity: A Causal or Protective Role?
Pulliam, D. A., Bhattacharya, A., & Remmen, H. V. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4950 · Cited by 33 · see citing works
Modulation of vascular endothelial cell senescence by integrin β4
Sun, C., Liu, X., Qi, L., Xu, J., Zhao, J., Zhang, Y., Zhang, S., & Miao, J. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22262 · Cited by 31 · see citing works
Piyanova, A., Albayram, Ö., Rossi, C. A., Farwanah, H., Michel, K., Nicotera, P., Sandhoff, K., & Bilkei‐Gorzó, A. (2013) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2013.08.001 · Cited by 31 · see citing works
Picca, A., Lozanoska‐Ochser, B., Calvani, R., Coelho‐Júnior, H. J., Leewenburgh, C., & Marzetti, E. (2023) · Experimental Gerontology · doi:10.1016/j.exger.2023.112204 · Cited by 30 · see citing works
Zhang, X., Kunz, H., Gries, K. J., Hart, C. R., Polley, E. C., & Lanza, I. R. (2021) · The Journal of Physiology · doi:10.1113/jp281691 · Cited by 30 · see citing works
Cefis, M., Dargegen, M., Marcangeli, V., Taherkhani, S., Dulac, M., Leduc‐Gaudet, J., Mayaki, D., Hussain, S. N. A., & Gouspillou, G. (2024) · Acta Physiologica · doi:10.1111/apha.14119 · Cited by 28 · see citing works
Oxaloacetate decarboxylase FAHD1 – a new regulator of mitochondrial function and senescence
Etemad, S., Petit, M., Weiss, A. K. H., Schrattenholz, A. S., Baraldo, G., & Jansen‐Dürr, P. (2018) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2018.07.007 · Cited by 26 · see citing works
Self-citationCefis, M., Marcangeli, V., Hammad, R., Granet, J., Leduc‐Gaudet, J., Gaudreau, P., Trumpff, C., Huang, Q., Picard, M. A., Aubertin‐Leheudre, M., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.101968 · Cited by 26 · see citing works
Mitochondrial function in peripheral blood cells across the human lifespan
Ehinger, J. K., Westerlund, E., Frostner, E. Å., Karlsson, M., Paul, G., Sjövall, F., & Elmér, E. (2024) · npj Aging · doi:10.1038/s41514-023-00130-4 · Cited by 22 · see citing works
Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases
Park, K., & Lee, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.811701 · Cited by 24 · see citing works
Picca, A., Triolo, M., Wohlgemuth, S. E., Martenson, M. S., Mankowski, R. T., Anton, S. D., Marzetti, E., Leeuwenburgh, C., & Hood, D. A. (2023) · Cells · doi:10.3390/cells12010183 · Cited by 23 · see citing works
Skeletal muscle bioenergetics in aging and heart failure
Liu, S. Z., & Marcinek, D. J. (2016) · Heart Failure Reviews · doi:10.1007/s10741-016-9586-z · Cited by 23 · see citing works
Bioenergetics of the aging heart and skeletal muscles: Modern concepts and controversies
Tepp, K., Timohhina, N., Puurand, M., Klepinin, A., Chekulayev, V., Shevchuk, I., & Kaambre, T. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.04.001 · Cited by 21 · see citing works
Pharaoh, G. A., Brown, J. L., Ranjit, R., Ungvari, Z. I., & Remmen, H. V. (2020) · JCSM Rapid Communications · doi:10.1002/rco2.29 · Cited by 21 · see citing works
Muscle Pathology in Free-Ranging Stranded Cetaceans
Sierra, E., Monteros, A. E. D. L., Fernández, A., Díaz‐Delgado, J., Suárez‐Santana, C. M., Arbelo, M., Sierra, M. A., & Herraez, P. (2016) · Veterinary Pathology · doi:10.1177/0300985816660747 · Cited by 21 · see citing works
Effect of age on in vivo oxidative capacity in two locomotory muscles of the leg
Tevald, M. A., Foulis, S. A., & Kent, J. A. (2014) · AGE · doi:10.1007/s11357-014-9713-5 · Cited by 21 · see citing works
Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice
Guachalla, L. M., Ju, Z., Koziel, R., von Figura, G., Song, Z., Fusser, M., Epe, B., Jansen-Dűrr, P., & Rudolph, K. L. (2009) · Aging · doi:10.18632/aging.100030 · Cited by 21 · see citing works
Self-citationDysfonctions mitochondriales et vieillissement musculaire
Faitg, J., Reynaud, O., Leduc‐Gaudet, J., & Gouspillou, G. (2017) · médecine/sciences · doi:10.1051/medsci/20173311012 · Cited by 20 · see citing works
Muscular senescence in cetaceans: adaptation towards a slow muscle fibre phenotype
Sierra, E., Fernández, A., Monteros, A. E. D. L., Arbelo, M., de Quirós, Y. B., & Herraez, P. (2013) · Scientific Reports · doi:10.1038/srep01795 · Cited by 20 · see citing works
Oh, S. J., & Lee, M. (2022) · Journal of Korean Medical Science · doi:10.3346/jkms.2022.37.e276 · Cited by 18 · see citing works
Семенов, А. Н., Maksimov, E. G., Moysenovich, A. M., Yakovleva, M. A., Tsoraev, G. V., Ramonova, A. A., Shirshin, E. A., Sluchanko, N. N., Feldman, T. B., Rubin, A., et al. (2023) · Antioxidants · doi:10.3390/antiox12020413 · Cited by 18 · see citing works
Muscle characteristics in patients with chronic systemic inflammation
Beenakker, K. G. M., Duijnisveld, B. J., van der Linden, H. M. J., Visser, C. P. J., Westendorp, R. G. J., Butler-Browne, G. S., Nelissen, R. G. H. H., & Maier, A. B. (2012) · Muscle & Nerve · doi:10.1002/mus.23291 · Cited by 18 · see citing works
Gorgey, A. S., Lai, R. E., Khalil, R. E., Rivers, J. F., Cardozo, C. P., Chen, Q., & Lesnefsky, E. J. (2021) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01029.2020 · Cited by 19 · see citing works
Paradis, S., Charles, A., Georg, I., Goupilleau, F., Meyer, A., Kindo, M. J., LAVERNY, G., METZGER, D., & Gény, B. (2019) · Antioxidants · doi:10.3390/antiox8060168 · Cited by 17 · see citing works
Accumulation of lipofuscin in broiler chicken with wooden breast
Hasegawa, Y., Kawasaki, T., Maeda, N., YAMADA, M., Takahashi, N., Watanabe, T., & Iwasaki, T. (2021) · Animal Science Journal · doi:10.1111/asj.13517 · Cited by 16 · see citing works
Do UCP2 and mild uncoupling improve longevity?
Dikov, D., Aulbach, A., Muster, B., Dröse, S., Jendrach, M., & Bereiter‐Hahn, J. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.03.011 · Cited by 16 · see citing works
Low in vivo brain glucose consumption and high oxidative stress in accelerated aging
Borrás, C., Stvolinsky, S. L., López-Grueso, R., Федорова, Т. Н., Gambini, J., Болдырев, А. А., & Viña, J. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.06.019 · Cited by 16 · see citing works
- Authors
- Hütter, E., Skovbro, M., Lener, B., Prats, C., Rabøl, R., Dela, F., & Jansen‐Dürr, P.
- Affiliations
- Austrian Academy of Sciences (AT)
- University of Copenhagen (DK)
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2007-02-05
- Volume
- 6
- Issue
- 2
- Pages
- 245-256
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- OpenAlex
- W2007891985
- Cited by
- 149
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 13 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 10 · 2016: 13 · 2015: 11 · 2014: 10 · 2013: 8 · 2012: 10
- FWCI
- 3.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- muscle aging, oxidative stress, reactive oxygen species, mitochondrial dysfunction, lipofuscin accumulation, skeletal muscle, mitochondrial respiration, protein oxidative modification, free radical theory of aging, vastus lateralis, mitochondrial quality control
- MeSH terms
- Adult, Aged, Aging, Biopsy, Female, Humans, Lipofuscin, Male, Mitochondria, Oxygen Consumption, Reactive Oxygen Species, Oxidative Stress, Muscle, Skeletal, Cell Respiration
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
