Age-Associated Changes in Skeletal Muscle Regeneration: Effect of Exercise


Aim of the present short review is to provide a comprehensive update on age-associated skeletal muscle damage, regeneration, and effect of endurance and resistance type of exercise training on muscle regeneration. Decrease in muscle quantity and quality leads to disability in the aging population. The degradation rate of muscle proteins during aging increased about two times, and muscle strength and motor activity decreased at the same time. Aging induced sarcopenia is a result of decreased synthesis and increased degradation of muscle proteins, which leads to the slower turnover rate of these proteins, especially contractile proteins, and this, in turn, leads to the decrease in muscle strength. Muscle damage is mainly caused by excessive strain in contracting fibre and aging muscle is particularly sensitive to it. The decreased synthesis and increased degradation rate of contractile proteins are in accordance with the increase destructive processes in muscle and lead to the decrease in the regeneration capacity and development of sarcopenia in the elderly. Exercise training increases muscle mass, oxidative capacity, contracile quality, regeneration capacity and via this, physiological functioning of skeletal muscle is improved in the elderly.

Share and Cite:

Seene, T. and Kaasik, P. (2015) Age-Associated Changes in Skeletal Muscle Regeneration: Effect of Exercise. Advances in Aging Research, 4, 230-241. doi: 10.4236/aar.2015.46025.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Degenes, H. and Alway, S.E. (2006) Control of Muscle Size during Disuse, Disease, and Aging. International Journal of Sports Medicine, 27, 94-99.
[2] Kadi, F. and Ponsot, E. (2010) The Biology of Satellite Cells and Telomeres in Human Skeletal Muscle: Effects of Aging and Physical Activity. Scandinavian Journal of Medicine and Science in Sports, 20, 39-48.
[3] Roberts, M.D., Kerksick, C.M., Dalbo, V.J., Hassell, S.E., Tucker, P.S. and Brown, R. (2010) Molecular Attributes of Human Skeletal Muscle at Rest and after Unaccustomed Exercise: An Age Comparison. Journal of Strength and Conditioning Research, 24, 1161-1168.
[4] Bassaglia, Y. and Gautron, J. (1995) Fast and Slow Rat Muscles Degenerate and Regenerate Differentlya after Cruch Injury. Journal of Muscle Research and Cell Motility, 16, 420-429.
[5] Shultz, E. and Darr, K. (1990) The Role of Satellite Cells in Adaptive or Induced Fiber Transformations. In: Pette, D., Ed., The Dynamic State of Muscle Fibers, W. de Gruyter, Berlin, 667-681.
[6] Kaasik, P., Aru, M., Alev, K. and Seene, T. (2012) Aging and Regenerative Capacity of Skeletal Muscle in Rats. Current Aging Science, 5, 126-130.
[7] Verney, J., Kadi, F., Charifi, N., Feasson, L., Saafi, M.A., Castells, J., Piehl-Aulin, K. and Denis, C. (2008) Effects of Combined Lower Body Endurance and Upper Body Resistance Training on the Satellite Cell Pool in Elderly Subjects. Muscle & Nerve, 38, 1147-1154.
[8] Malatesta, M., Perdoni, F., Muller, S., Pellicciari, C. and Zancanaro, C. (2010) Pre-mRNA Processing Is Partially Impaired in Satellite Cell Nuclei from Aged Muscles. Journal of Biomedicine & Biotehnology, 2010, Article ID: 410405.
[9] Ono, Y., Boldrin, L., Knopp, P., Morgan, J.E. and Zammit, P.S. (2010) Muscle Satellite Cells Are a Functionally Heterogeneous Population in Both Somite-Derived and Branchiomeric Muscles. Development Biology, 337, 29-41.
[10] Tatsumi, R. (2010) Mechano-Biology of Skeletal Muscle Hypertrophy and Regeneration: Possible Mechanism of Stretch-Induced Activation of Resident Myogenic Stem Cells. Animal Science Journal, 81, 11-20.
[11] Carlson, B.M., Dedkov, E.I., Borisov, A.B. and Faulkner, J.A. (2001) Skeletal Muscle Regeneration in Very Old Rats. The Journal of Gerontology. Series A, Biological Sciences and Medical Sciences, 56, B224-B233.
[12] Conboy, I.M., Conboy, M.J., Wagers, A.J., Girma, E.R., Weissman, I.L. and Rando, T.A. (2005) Rejuvenation of Aged Progenitor Cells by Exposure to a Young Systemic Environment. Nature, 433, 760-764.
[13] Rader, E.P. and Faulkner, J.A. (2006) Recovery from Contraction-Induced Injury Is Impaired in Weight-Bearing Muscles of Old Male Mice. Journal of Applied Physiology, 100, 656-661.
[14] Kaasik, P., Umnova, M., Pehme, A., Alev, K., Aru, M., Selart, A. and Seene, T. (2007) Ageing and Dexamethasone Associated Sarcopenia: Peculiarities of Regeneration. The Journal of Steroid Biochemistry and Molecular Biology, 105, 85-90.
[15] Evans, W.J. (2010) Skeletal Muscle Loss: Cachexia, Sarcopenia, and Inactivity. The American Journal of Clincal Nutrition, 91, 1123S-1127S.
[16] Evans, W.J., Paolisso, G., Abbatecola, A.M., Corsonello, A., Bustacchini, S., Strollo, F. and Lattanzio, F. (2010) Frailty and Muscle Metabolism Dysregulation in the Elderly. Biogerontology, 11, 527-536.
[17] Seene, T. and Kaasik, P. (2012) Muscle Weakness in the Elderly: Role of Sarcopenia, Dynapenia, and Possibilities for Rehabilitation. European Review of Aging and Physical Activity, 9, 109-117.
[18] Mechling, H. and Netz, Y. (2009) Aging and Inactivity-Capitalizing on the Protective Effect of Planned Physical Activity in Old Age. European Review of Aging and Physical Activity, 6, 89-97.
[19] Lauretani, F., Russo, C.R., Bandinelli, S., Bartali, B., Cavazzini, C., Di Iorio, A., Corsi, A.M., Rantanen, T., Guralnik, J.M. and Ferrucci, L. (2003) Age-Associated Changes in Skeletal Muscles and Their Effect on Mobility: An Operational Diagnosis of Sarcopenia. Journal of Applied Physiology, 9, 1851-1860.
[20] Clark, B.C. and Manini, T.M. (2010) Functional Concequences of Sacropenia and Dynapenia in the Elderly. Current Opinion in Clinical Nutrition and Metabolic Care, 13, 271-276.
[21] Seene, T., Kaasik, P. and Riso, E.M. (2012) Review on Aging, Unloading and Reloading: Changes in Skeletal Muscle Quantity and Quality. Archives of Gerontology and Geriatrics, 54, 374-380.
[22] Haus, J.M., Carrithers, J.A., Trappe, S.W. and Trappe, T.A. (2007) Collagen, Cross-Linking, and Advanced Glycation End Products in Aging Human Skeletal Muscle. Journal of Applied Physiology, 103, 2068-2076.
[23] Trappe, T. (2009) Influence of Aging and Long-Term Unloading on the Structure and Function of Human Skeletal Muscle. Applied Physiology, Nutrition, and Metabolism, 34, 459-464.
[24] Pasiakos, S.M., Vislocky, L.M., Carbone, J.W., Altieri, N., Konopelski, K., Freake, H.C., Anderson, J.M., Ferrando, A.A., Wolfe, R.R. and Rodriguez, N.R. (2010) Acute Energy Deprivation Affects Skeletal Muscle Protein Synthesis Associated Intracellular Signaling Proteins in Physically Active Adults. The Journal of Nutrition, 140, 745-751.
[25] Siu, P.M., Pistilli, E.E. and Alway, S.E. (2008) Age-Dependent Increase in Oxidative Stress in Gastrocnemius Muscle with Unloading. Journal of Applied Physiology, 105, 1695-1705.
[26] Leeuwenburgh, C., Gurley, C.M., Strotman, B.A. and Dupont-Versteegden, E.E. (2005) Age-Related Differences in Apoptosis with Disuse Atrophy in Soleus Muscle. American Journal of Physiology. Regulatory Integrative and Comparative Physiology, 288, R1288-R1296.
[27] Ogata, T., Machida, S., Oishi, Y., Higuchi, M. and Muraoka, I. (2009) Differential Cell Death Regulation between Adult-Unloaded and Aged Rat Soleus Muscle. Mechanisms of Ageing and Development, 130, 328-336.
[28] Buford, T.W., Anton, S.D., Judge, A.R., Marzetti, E., Wohlgemuth, S.E., Carter, C.S., Leeuwenburgh, C., Pahor, M. and Manini, T.M. (2010) Models of Accelerated Sarcopenia: Critical Pieces for Solving the Puzzle of Age-Related Muscle Atrophy. Ageing Research Reviews, 9, 369-383.
[29] Clark, B.C. and Manini, T.M. (2008) Sarcopenia ≠ Dynapenia. The Journal of Gerontology. Series A, Biological Sciences and Medical Sciences, 63, 829-834.
[30] Gonzales, E., Messi, M.L. and Delbono, O. (2000) The Specific Force of Single Intact Extensor Digitorum Longus and Soleus Mouse Muscle Fibers Declines with Aging. The Journal of Membrane Biology, 178, 175-183.
[31] Stackhouse, S.K., Stevens, J.E., Lee, S.C., Pearce, K.M., Snyder-Mackler, L. and Binder-Macleod, S.A. (2001) Maximum Voluntary Activation in Nonfatigued and Fatigued Muscle of Young and Elderly Individuals. Physical Therapy, 81, 1102-1109.
[32] Weisleder, N., Brotto, M., Komazaki, S., Pan, Z., Zhao, X., Nosek, T., Parness, J., Takeshima, H. and Ma, J. (2006) Muscle Aging Is Associated with Compramised Ca2+ Spark Signaling and Segregated Intracellular Ca2+ Release. The Journal of Cell Biology, 174, 639-645.
[33] Manini, T.M. and Clark, B.C. (2012) Dynapenia and Aging: An Update. The Journal of Gerontology. Series A, Biological Sciences and Medical Sciences, 67, 28-40.
[34] Gandevia, S.C. (2001) Spinal and Supraspinal Factors in Human Muscle Fatigue. Physiological Reviews, 81, 1725-1789.
[35] Perrey, S. and Rupp, T. (2009) Altitude-Induced Changes in Muscle Contractile Properies. High Altitude Medicine & Biology, 10, 175-182.
[36] Gibala, M. (2009) Molecular Responses to High-Intensity Interval Exercise. Applied Physiology, Nutrition, and Metabolism, 34, 428-432.
[37] Seene, T., Umnova, M., Kaasik, P., Alev, K. and Pehme, A. (2008) Overtraining Injuries in Athletic Population. In: Tiidus, P.M., Ed., Skeletal Muscle Damage and Repair, Human Kinetics, Champaign, 173-184.
[38] Duguez, S., Féasson, L., Denis, C. and Freyssenet, D. (2002) Mitochondrial Biogenesis during Skeletal Muscle Regeneration. American Journal of Physiology. Endocrinology and Metabolism, 282, E802-E809.
[39] Lowery, L. and Forsythe, C.E. (2006) Protien and Overtraining: Potential Applications for Free-Living Athletes. Journal of the International Society of Sports Nutrition, 3, 42-50.
[40] Ament, W. and Verkere, G.J. (2009) Exercise and Fatigue. Sports Medicine, 39, 389-422.
[41] Neto, J.C.R., Lira, F.S., Oyama, L.M., Zanchi, N.E., Yamashita, A.S., Batista Jr., M.L., Oller do Nascimento, C.M. and Seelaender, M. (2009) Exhaustive Exercise Causes an Anti-Inflammatory Effect in Skeletal Muscle and a Pro-Inflammatory Effect in Adipose Tissue in Rats. European Journal of Applied Physiology, 106, 697-704.
[42] Liu, Y. and Steinacker, J.M. (2001) Changes in Skeletal Muscle Heat Shock Proteins: Pathological Significance. Frontiers in Bioscience, 6, D12-D25.
[43] Steinacker, J.M. and Liu, Y. (2002) Stress Proteins and Applied Exercise Physiology. In: Locke, M. and Noble, E.G., Eds., Exercise and Stress Response: The Role of Stress Proteins, CRC Press, Boca Raton, 197-216.
[44] Kurek, J.B., Bower, J.J., Romanella, M., Koentgen, F., Murphy, M. and Austin, L. (1997) The Role of Leukemia Inhibitory Factor in Skeletal Muscle Regeneration. Muscle & Nerve, 20, 815-822.<815::AID-MUS5>3.0.CO;2-A
[45] Holloszy, J.O. and Booth, F.W. (1976) Biochemical Adaptations to Endurance Exercise in Muscle. Annual Review of Physiology, 38, 273-291.
[46] Baldwin, K.M. and Haddad, F. (2002) Skeletal Muscle Plasticity: Cellular and Molecular Responses to Altered Physical Activity Paradigms. American Journal of Physical Meicine & Rehabilitation, 81, S40-S51.
[47] Magaudda, L., Di Mauro, D., Trimarchi, F. and Anastasi, G. (2004) Effects of Physical Exercise on Skeletal Muscle Fiber: Ultrastructural and Molecular Aspects. Basic and Applied Myology, 14, 17-21.
[48] Seene, T., Kaasik, P. and Alev, K. (2011) Muscle Protein Turnover in Endurance Training: A Review. International Journal of Sports Medicine, 32, 905-911.
[49] Seene, T., Kaasik, P. and Umnova, M. (2009) Structural Rearrangements in Contractile Apparatus and Resulting Skeletal Muscle Remodelling: Effect of Exercise Training. Journal of Sports Medicine and Physical Fitness, 49, 410-423.
[50] Ljubicic, V., Joseph, A.M., Saleem, A., Uguccioni, G., Collu-Marchese, M., Lai, R.Y., Nguyen, L.M. and Hood, D.A. (2010) Transcriptional and Post-Transcriptional Regulation of Mitochondrial Biogenesis in Skeletal Muscle: Effects of Exercise and Aging. Biochimica et Biophysica Acta, 1800, 223-234.
[51] Sagiv, M., Goldhammer, E., Ben-Sira, D. and Amir, R. (2010) Factors Defining Oxygen Uptake at Peak Exercie in Aged People. European Review of Aging and Physical Activity, 7, 1-2.
[52] Seppet, E.K., Eimre, M., Anmann, T., Seppet, E., Peet, N., Käämbre, T., Paju, K., Piirsoo, A., Kuznetsov, A.V., Vendelin, M., Gellerich, F.N., Zierz, S. and Saks, V.A. (2005) Intracellular Energetic Units in Healthy and Diseased Hearts. Experimental and Clinical Cardiology, 10, 173-183.
[53] Seene, T. and Kaasik, P. (2013) Muscle Damage and Regeneration: Response to Exercise Training. Health, 5, 136-145.
[54] Seene, T., Kaasik, P., Alev, K., Pehme, A. and Riso, E.M. (2004) Composition and Turnover of Contractile Proteins in Volume-Overtrained Skeletal Muscle. International Journal of Sports Medicine, 25, 438-445.
[55] Folland, J.P. and Williams, A.G. (2007) The Adaptations to Strength Training: Morphological and Neurological Contributions to Increased Strength. Sports Medicine, 37, 145-168.
[56] Sjöström, M., Johansson, C. and Lorentzon, R. (1988) Muscle Pathomorphology in M. Quadericeps of Marathon Runners. Early Signs of Strain Disease or Functional Adaptation? Acta Physiologica Scandinavica, 132, 537-541.
[57] Moore, D.R., Atherton, P.J., Rennie, M.J., Tarnopolsky, M.A. and Phillips, S.M. (2011) Resistance Exercise Enhances mTOR and MAPK Signalling in Human Muscle Over That Seen at Rest after Bolus Protein Ingestion. Acta Physiologica, 201, 365-372.
[58] Schoenfeld, B.J. (2012) Does Exercise-Induced Muscle Damage Play a Role in Skeletal Muscle Hypertrophy? Journal of Strength and Conditioning Research, 26, 1441-1453.
[59] Mauro, A. (1961) Satellite Cell of Skeletal Muscle Fibres. The Journal of Biophysical and Biochemical Cytology, 9, 493-495.
[60] Charge, S.B. and Rudnicki, M.A. (2004) Cellular and Molecular Regulation of Muscle Regeneration. Physiological Review, 84, 209-238.
[61] Umnova, M. and Seene, T. (1991) The Effect of Increased Functional Load on the Activation of Satellite Cells in the Skeletal Muscle of Adult Rats. International Journal of Sports Medicine, 12, 501-504.
[62] Grounds, M.D. (1999) Muscle Regeneration: Molecular Aspects and Therapeutic Implications. Current Opinion in Neurology, 12, 535-543.
[63] Broholm, C. and Pedersen, B.K. (2010) Leukaemia Inhibitory Factor—An Exercise Induced Myokine. Exercise Immunology Review, 16, 77-85.
[64] Angione, A.R., Jiang, C., Pan, D., Wang, Y.X. and Kuang, S. (2011) PPARδ Regulates Satellite Cell Proliferation and Skeletal Muscle Regeneration. Skeletal Muscle, 1, 33.
[65] Zeng, L., Akasaki, Y., Sato, K., Ouchi, N., Izumiya, Y. and Walsh, K. (2010) Insulin-Like 6 Is Induced by Muscle Injury and Functions as a Regenerative Factor. The Journal of Biological Chemistry, 285, 36060-36069.
[66] Martins, K.J., Gordon, T., Pette, D., Dixon, W.T., Foxcroft, G.R., Maclean, I.M. and Putman, C.T. (2006) Effect of Satellite Cell Ablation on Low-Frequency-Stimulated Fast-to-Slow Fibre-Type Transitions in Rat Skeletal Muscle. The Journal of Physiology, 572, 281-294.
[67] Gibson, M.C. and Schultz, E. (1982) The Distribution of Satellite Cells and Their Relationship to Specific Fiber Types in Soleus and Extensor Digitorum Longus Muscles. The Anatomical Record, 202, 329-337.
[68] Mackrell, J.G. and Cartee, G.D. (2012) A Novel Method to Measure Glucose Uptake and Myosin Heavy Chain Isoform Expression of Single Fibers from Rat Skeletal Muscle. Diabetes, 61, 995-1003.
[69] Gibson, M.C. and Schultz, E. (1983) Age-Related Differences in Absolute Numbers of Skeletal Muscle Satellite Cells. Muscle & Nerve, 6, 574-580.
[70] Putman, C.T., Düsterhöft, S. and Pette, D. (2001) Satellite Cell Proliferation in Low Frequency-Stimulated Fast Muscle of Hypothyroid Rat. American Journal of Physiology. Cell Physiology, 279, C682-C690.
[71] Putman, C.T., Sultan, K.R., Wassmer, T., Bamford, J.A., Skorjanc, D. and Pette, D. (2001) Fiber-Type Transitions and Satellite Cell Activation in Low-Frequency-Stimulated Muscles of Young and Aging Rats. The Journal of Gerontology. Series A, Biological Sciences and Medical Sciences, 56, B510-B519.
[72] Apell, H.J., Forsberg, S. and Hollmann, W. (1988) Satellite Cell Activation in Human Skeletal Muscle after Training: Evidence for Muscle Fiber Neoformation. International Journal of Sports Medicine, 9, 297-299.
[73] Winder, W.W. and Hardie, D.G. (1996) Inactivation of Acetyl-CoA Carboxylase and Activation of AMP-Activated Protein Kinase in Muscle during Exercise. The American Journal of Physiology, 270, E299-304.
[74] Hardie, D.G. and Sakamoto, K. (2006) AMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle. Physiology, 21, 48-60.
[75] McGee, S.L., Kristy, J., Mustard, D., Hardie, D.G. and Baar, K. (2008) Normal Hypertrophy Accompanied by Phosphoryation and Activation of AMP-Activated Protein Kinase α1 Following Overload in LKB1 Knockout Mice. The Journal of Physiology, 586, 1731-1741.
[76] van Wessel, T., de Haan, A., van der Laarse, W.J. and Jaspers, R.T. (2010) The Muscle Fiber Type-Fiber Size Paradox: Hypertrophy or Oxidative Metabolism? European Journal of Applied Physiology, 110, 665-694.
[77] Bodine, S.C., Stitt, T.N., Gonzalez, M., Kline, W.O., Stover, G.L., Bauerlein, R., Zlotchenko, E., Scrimgeour, A., Lawrence, J.C., Glass, D.J. and Yancopoulos, G.D. (2001) Akt/mTOR Pathway Is a Crucial Regulator of Skeletal Muscle Hypertrophy and Can Prevent Muscle Atrophy in Vivo. Nature Cell Biology, 3, 1014-1019.
[78] Stitt, T.N., Drujan, D., Clarke, B.A., Panaro, F., Timofeyva, Y., Kline, W.O., Gonzalez, M., Yancopoulos, G.D. and Glass, D.J. (2004) The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription Factors. Molecular Cell, 14, 395-403.
[79] van der Vusse, G.J., Glatz, J.F., Stam, H.C. and Reneman, R.S. (1992) Fatty Acid Homeostasis in The Normoxic and Ischemic Heart. Physiological Reviews, 72, 881-940.
[80] Seene, T.L. and Umnova, M. (1992) Relations between the Changes in the Turnover Rate of Contractile Proteins, Activation of Satellite Cells and Ultra-Structural Response of Neuromuscular Junctions in the Fast-Oxidative-Glucolytic Muscle Fibres in Endurance Trained Rats. Basic and Applied Myology, 2, 39-46.
[81] Alev, K., Kaasik, P., Pehme, A., Aru, M., Parring, A.-M., Selart, A. and Seene, T. (2009) Physiological Role of Myosin Light and Heavy Chain Isoforms in Fast- and Slow-Twitch Muscles: Effect of Exercise. Biology of Sport, 26, 215-234.
[82] Pette, D. (2001) Historical Perspectives: Plasticity of Mammalian Skeletal Muscle. Journal of Applied Physiology, 90, 1119-1124.
[83] Hernandez, J.M., Fedele, M.J. and Farrell, P.A. (2000) Time Course Evaluation of Protein Synthesis and Glucose Uptake after Acute Resistance Exercise in Rats. Journal of Applied Physiology, 88, 1142-1149.
[84] Allen, D.L., Roy, R.R. and Edgerton, V.R. (1999) Myonuclear Domains in Muscle Adaptation and Disease. Muscle & Nerve, 22, 1350-1360.<1350::AID-MUS3>3.0.CO;2-8
[85] Seene, T., Pehme, A., Alev, K., Kaasik, P., Umnova, M. and Aru, M. (2010) Effects of Resistance Training on Fast- and Slow-Twitch Muscles in Rats. Biology of Sport, 27, 221-229.
[86] Fell, J.W. and Williams, A.D. (2008) The Effect of Aging on Skeletal-Muscle Recovery from Exercise: Possible Implications for the Aging Athlete. Journal of Aging and Physical Activity, 16, 97-115.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.