Exercise training decreases DNA damage and increases DNA repair and resistance against oxidative stress of proteins in aged rat skeletal muscle
Abstract
Regular physical exercise retards a number of age-associated disorders, in spite of the paradox that free radical generation is significantly enhanced with exercise. Eight weeks of treadmill running resulted in nearly a 40% increase in maximal oxygen uptake in both middle-aged (20-month-old) and aged (30-month-old) rats. The age-associated increase in 8-hydroxy-2'-deoxyguanosine (8-OHdG) content was significantly attenuated in gastrocnemius muscle by exercise. The 8-OHdG repair, as measured by the excision of 32P-labeled damaged oligonucleotide, increased in muscle of exercising animals. The reactive carbonyl derivatives (RCD) of proteins did not increase with aging. However, when the muscle homogenate was exposed to a mixture of 1 mM iron sulfate and 50 mM ascorbic acid, the muscle of old control animals accumulated more RCD than that of the trained or adult groups. The chymotrypsin-like activity of proteasome complex increased in muscle of old trained rats. We suggest that regular exercise-induced adaptation attenuates the age-associated increase in 8-OHdG levels, and increases the activity of DNA repair and resistance against oxidative stress in proteins.
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Exercise is an efficient strategy for delaying aging through mechanisms such as DNA damage and oxidative stress.
“Exercise is an efficient strategy for delaying aging330 through various mechanisms, such as DNA damage331 and oxidative stress.332”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [331]
Eight weeks of treadmill running attenuated the age-associated increase in DNA damage (8-OHdG content) within skeletal muscle of 30-month-old rats.
“Impressively, 8 wk of treadmill running attenuated the age-associated increase in DNA damage (8-OHdG content) within skeletal muscle of 30-month-old rats (14).”
From Exercise Counters the Age-Related Accumulation of Senescent Cells (2022) · cites this paper as [14]
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
The Free Radical Theory of Aging Matures
BECKMAN, K. B., & AMES, B. N. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.547 · Cited by 3,879 · see citing works
Protein Oxidation in Aging, Disease, and Oxidative Stress
Berlett, B. S., & Stadtman, E. R. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.33.20313 · Cited by 3,339 · see citing works
Oxidative Stress, Caloric Restriction, and Aging
Sohal, R. S., & Weindruch, R. H. (1996) · Science · doi:10.1126/science.273.5271.59 · Cited by 3,133 · see citing works
Stadtman, E. R. (1992) · Science · doi:10.1126/science.1355616 · Cited by 2,701 · see citing works
Gene expression profile of aging and its retardation by caloric restriction
Lee, C.-K., Klopp, R. G., Weindruch, R., & Prolla, T. A. (1999) · Science · doi:10.1126/science.285.5432.1390 · Cited by 1,473 · see citing works
Degradation of oxidized proteins in mammalian cells
Grune, T., Reinheckel, T., & Davies, K. J. A. (1997) · The FASEB Journal · doi:10.1096/fasebj.11.7.9212076 · Cited by 835 · see citing works
Mutagenesis by 8-oxoguanine: an enemy within
Grollman, A. P., & Moriya, M. (1993) · Trends in Genetics · doi:10.1016/0168-9525(93)90089-z · Cited by 807 · see citing works
The role of 8-hydroxyguanine in carcinogenesis
Floyd, R. A. (1990) · Carcinogenesis · doi:10.1093/carcin/11.9.1447 · Cited by 721 · see citing works
Genetic analysis of ageing: role of oxidative damage and environmental stresses
Martin, G. M., Austad, S. N., & Johnson, T. E. (1996) · Nature Genetics · doi:10.1038/ng0596-25 · Cited by 641 · see citing works
Purification of two high molecular weight proteases from rabbit reticulocyte lysate.
Hough, R., Pratt, G., & Rechsteiner, M. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47564-3 · Cited by 545 · see citing works
Cloning and characterization of a mammalian 8-oxoguanine DNA glycosylase
Rosenquist, T. A., Zharkov, D. O., & Grollman, A. P. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.14.7429 · Cited by 485 · see citing works
Anstey, K., & Christensen, H. (2000) · Gerontology · doi:10.1159/000022153 · Cited by 377 · see citing works
Adaptation to exercise-induced oxidative stress: from muscle to brain.
Radak, Z. O., Taylor, A. W., Ohno, H., & Goto, S. (2001) · PubMed · Cited by 292 · see citing works
Self-citationRadak, Z. O., Kaneko, T., Tahara, S., Nakamoto, H., Ohno, H., Sasvári, M., Nyakas, C. J., & Goto, S. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00038-6 · Cited by 273 · see citing works
Self-citationNakamura, A., & Goto, S. (1996) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a021306 · Cited by 160 · see citing works
Self-citationExercise and its role in the prevention and rehabilitation of cardiovascular disease
Miller, T. D., Balady, G. J., & Fletcher, G. F. (1997) · Annals of Behavioral Medicine · doi:10.1007/bf02892287 · Cited by 153 · see citing works
DNA damage, repair, and antioxidant systems in brain regions: a correlative study
Cardozo‐Pelaez, F., Brooks, P. J., Stedeford, T. J., Song, S., & Sanchez‐Ramos, J. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00172-6 · Cited by 131 · see citing works
Self-citationAge-related changes in the 20S and 26S proteasome activities in the liver of male F344 rats.
Hayashi, T., & Goto, S. (1998) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(98)00011-6 · Cited by 125 · see citing works
Self-citationKaneko, T., Tahara, S., & Matsuo, M. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00622-3 · Cited by 108 · see citing works
Self-citationCellular and molecular mechanisms of aging
Dice, J. F. (1993) · Physiological Reviews · doi:10.1152/physrev.1993.73.1.149 · Cited by 103 · see citing works
Christensen, H. M., & Mackinnon, A. J. (1993) · Age and Ageing · doi:10.1093/ageing/22.3.175 · Cited by 100 · see citing works
Radak, Z. O., Asano, K., Lee, K.-C., Ohno, H., Nakamura, A., Nakamoto, H., & Goto, S. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00350-4 · Cited by 88 · see citing works
Self-citationImplications of Protein Degradation in Aging
Goto, S., Takahashi, R., Kumiyama, A., Radak, Z. O., Hayashi, T., Takenouchi, M., & Abe, R. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb05635.x · Cited by 83 · see citing works
Self-citationAge-associated, oxidatively modified proteins: A critical evaluation
Goto, S., & Nakamura, A. (1997) · AGE · doi:10.1007/s11357-997-0008-y · Cited by 48 · see citing works
Self-citationCardozo, C. P., Vinitsky, A., Michaud, C., et al. (1994) · Biochemistry · doi:10.1021/bi00187a014 · Cited by 46 · see citing works
Reduction of 8-hydroxyguanine in human leukocyte DNA by physical exercise
Asami, S., Hirano, T., Yamaguchi, R., & Itoh, H. (1998) · Free Radical Research · doi:10.1080/10715769800300621 · Cited by 43 · see citing works
Takahashi, R., & Goto, S. (1987) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(87)90559-5 · Cited by 33 · see citing works
Self-citationBiological Implications of Protein Oxidation
Goto, S., Radak, Z. O., & Takahashi, R. (2002) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789812775733_0020 · Cited by 11 · see citing works
Self-citation
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Cited by
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Li, X., Li, C., Zhang, W., Wang, Y., Qian, P., & Huang, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01502-8 · Cited by 1,443 · see citing works
The mitochondrial energy transduction system and the aging process
Navarro, A., & Boveris, A. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00213.2006 · Cited by 646 · see citing works
Exercise, oxidative stress and hormesis
Radak, Z., Chung, H. Y., Koltai, E., Taylor, A. W., & Goto, S. (2008) · Ageing Research Reviews · doi:10.1016/j.arr.2007.04.004 · Cited by 638 · see citing works
Self-citationSystemic adaptation to oxidative challenge induced by regular exercise
Radak, Z., Chung, H. Y., & Goto, S. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.01.029 · Cited by 623 · see citing works
Self-citationVaynman, S., & Gomez-Pinilla, F. (2005) · Neurorehabilitation and Neural Repair · doi:10.1177/1545968305280753 · Cited by 420 · see citing works
Exercise Attenuates the Major Hallmarks of Aging
Garatachea, N., Pareja-Galeano, H., Sanchis-Gomar, F., Santos-Lozano, A., Fiuza-Luces, C., Morán, M., Emanuele, E., Joyner, M. J., & Lucia, A. (2015) · Rejuvenation Research · doi:10.1089/rej.2014.1623 · Cited by 413 · see citing works
Exercise modulates oxidative stress and inflammation in aging and cardiovascular diseases
Sallam, N., & Laher, I. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7239639 · Cited by 334 · see citing works
Exercise alters SIRT1, SIRT6, NAD and NAMPT levels in skeletal muscle of aged rats
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
Self-citationExercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue
Schafer, M. J., White, T. A., Evans, G., Tonne, J. M., Verzosa, G. C., Stout, M. B., Mazula, D. L., Palmer, A. K., Baker, D. J., Jensen, M. D., et al. (2016) · Diabetes · doi:10.2337/db15-0291 · Cited by 267 · see citing works
Exercise sustains the hallmarks of health
Qiu, Y., Fernández-García, B., Lehmann, H. I., Li, G., Kroemer, G., López-Otín, C., & Xiao, J. (2023) · Journal of Sport and Health Science · doi:10.1016/j.jshs.2022.10.003 · Cited by 270 · see citing works
Altered proteasome structure, function, and oxidation in aged muscle.
Ferrington, D. A., Husom, A. D., & Thompson, L. V. (2005) · The FASEB Journal · doi:10.1096/fj.04-2578fje · Cited by 259 · see citing works
Aging Hallmarks: The Benefits of Physical Exercise
Rebelo-Marques, A., De Sousa Lages, A., Andrade, R., Ribeiro, C. F., Mota-Pinto, A., Carrilho, F., & Espregueira-Mendes, J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00258 · Cited by 246 · see citing works
Hood, D. A. (2009) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/h09-045 · Cited by 242 · see citing works
Age-related differences in apoptosis with disuse atrophy in soleus muscle
Leeuwenburgh, C., Gurley, C. M., Strotman, B. A., & Dupont-Versteegden, E. E. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00576.2004 · Cited by 231 · 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
The effects of dietary restriction on oxidative stress in rodents
Walsh, M. E., Shi, Y., & Van Remmen, H. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.037 · Cited by 181 · see citing works
Physical Activity and Cancer Prevention: Pathways and Targets for Intervention
Rogers, C. J., Colbert, L. H., Greiner, J. W., Perkins, S. N., & Hursting, S. D. (2008) · Sports Medicine · doi:10.2165/00007256-200838040-00002 · Cited by 170 · see citing works
Koltai, E., Hart, N., Taylor, A. W., Goto, S., Ngo, J. K., Davies, K. J. A., & Radak, Z. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00337.2011 · Cited by 152 · see citing works
Mahoney, D. J., Rodriguez, C., Devries, M., Yasuda, N., & Tarnopolsky, M. A. (2004) · Muscle & Nerve · doi:10.1002/mus.20004 · Cited by 140 · see citing works
Muscle wasting and aging: Experimental models, fatty infiltrations, and prevention
Brioche, T., Pagano, A. F., Py, G., & Chopard, A. (2016) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2016.04.006 · Cited by 129 · see citing works
Does exercise reduce brain oxidative stress? A systematic review
Camiletti‐Moirón, D., Aparicio, V. A., Aranda, P., & Radak, Z. (2013) · Scandinavian Journal of Medicine & Science in Sports · doi:10.1111/sms.12065 · Cited by 104 · see citing works
Self-citationEffects of exercise on cellular and tissue aging
Carapeto, P. V., & Aguayo-Mazzucato, C. (2021) · Aging · doi:10.18632/aging.203051 · Cited by 107 · see citing works
Englund, D. A., Zhang, X., Aversa, Z., & LeBrasseur, N. K. (2021) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2021.111595 · Cited by 94 · see citing works
Inactivity‐induced oxidative stress: A central role in age‐related sarcopenia?
Derbré, F., Gratas‐Delamarche, A., Gómez‐Cabrera, M. C., & Viña, J. (2014) · European Journal of Sport Science · doi:10.1080/17461391.2011.654268 · Cited by 89 · see citing works
Is exercise a senolytic medicine? A systematic review
Chen, X., Yi, Z., Wong, G. T., Hasan, K. M. M., Kwan, J. S., Ma, A. C., & Chang, R. C. (2021) · Aging Cell · doi:10.1111/acel.13294 · Cited by 88 · see citing works
Shefer, G., Rauner, G., Stuelsatz, P., Benayahu, D., & Yablonka‐Reuveni, Z. (2013) · The FEBS Journal · doi:10.1111/febs.12228 · Cited by 72 · see citing works
Ziaaldini, M. M., Koltai, E., Csende, Z., Goto, S., Boldogh, I., Taylor, A. W., & Radak, Z. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.04.008 · Cited by 72 · see citing works
Stigger, F. S., Zago Marcolino, M. A., Portela, K. M., & Plentz, R. D. M. (2019) · The Journals of Gerontology: Series A · doi:10.1093/gerona/gly173 · Cited by 68 · see citing works
Exercise Counters the Age-Related Accumulation of Senescent Cells
Zhang, X., Englund, D. A., Aversa, Z., Jachim, S. K., White, T. A., & LeBrasseur, N. K. (2022) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000302 · Cited by 63 · see citing works
Recent physical activity in relation to DNA damage and repair using the comet assay
Cash, S. W., Beresford, S. A. A., Vaughan, T. L., Heagerty, P. J., Bernstein, L., White, E., & Neuhouser, M. L. (2014) · Journal of Physical Activity and Health · doi:10.1123/jpah.2012-0278 · Cited by 46 · see citing works
Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence
Carapeto, P., Iwasaki, K., Hela, F., Kahng, J., Alves-Wagner, A. B., Middelbeek, R. J. W., Hirshman, M. F., Rutter, G. A., Goodyear, L. J., & Aguayo-Mazzucato, C. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01130-8 · Cited by 35 · see citing works
- Authors
- Radák, Z., Naito, H., Kaneko, T., Tahara, S., Nakamoto, H., Takahashi, R., Cardozo-Pelaez, F., & Goto, S.
- Affiliations
- Tokyo Metropolitan Institute of Gerontology (JP)
- Toho University (JP)
- ORCID
- Takahashi, Ryoya
- Venue
- Pfl�gers Archiv European Journal of Physiology
- Published
- 2002-11-01
- Volume
- 445
- Issue
- 2
- Pages
- 273-278
- ISSN
- 0031-6768 (ISSN-L)
- OpenAlex
- W2162808674
- Cited by
- 269
- References
- 29
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 9 · 2023: 4 · 2022: 8 · 2021: 12 · 2020: 7 · 2019: 9 · 2018: 22 · 2017: 12 · 2016: 12 · 2015: 19 · 2014: 8 · 2013: 12 · 2012: 9
- FWCI
- 11.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Pflügers Archiv - European Journal of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- 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
- exercise training, aging, skeletal muscle, DNA damage, DNA repair, oxidative stress, 8-hydroxy-2'-deoxyguanosine, protein carbonylation, proteasome activity, treadmill running, gastrocnemius, VO2max
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Aging, Animals, Body Weight, Deoxyguanosine, DNA Damage, DNA Repair, Male, Muscle Proteins, Oxygen Consumption, Physical Conditioning, Animal, Rats, Inbred F344, Oxidative Stress, Muscle, Skeletal, Rats
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