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Aging of Skeletal Muscle Fibers
Open accessAbstract
Aging has become an important topic for scientific research because life expectancy and the number of men and women in older age groups have increased dramatically in the last century. This is true in most countries of the world including the Republic of Korea and the United States. From a rehabilitation perspective, the most important associated issue is a progressive decline in functional capacity and independence. Sarcopenia is partly responsible for this decline. Many changes underlying the loss of muscle mass and force-generating capacity of skeletal muscle can be understood at the cellular and molecular levels. Muscle size and architecture are both altered with advanced adult age. Further, changes in myofibers include impairments in several physiological domains including muscle fiber activation, excitation-contraction coupling, actin-myosin cross-bridge interaction, energy production, and repair and regeneration. A thorough understanding of these alterations can lead to the design of improved preventative and rehabilitative interventions, such as personalized exercise training programs.
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“These changes are also accompanied by a diminished regenerative capacity of the muscle due to a loss in the number and activity of satellite cells in type II “fast” fibers [14,16,17].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [17]
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“However, a direct relationship between increased intermuscular fat and age-related muscle weakness has not been established [51].”
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“These changes are also found in aged skeletal muscles, where there is a shift from fast to slow fiber types (Holloszy et al., 1991; Larsson and Ansved, 1995; Miljkovic et al., 2015; Thompson, 1994).”
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“…Nutrition, and Metabolism Draft 3 INTRODUCTION 46 47 Aging is accompanied by a progressive decline in skeletal muscle mass quantity and 48 quality, which negatively impact individuals’ body composition, muscle strength, and physical 49 function, leading to clinical problems (Miljkovic et al. 2015).”
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“Sarcopenia is characterized by the MHC shift of fast (type II)-to-slow (type I) twitchmuscle fibers as well as the CSA reduction of muscle fibers [3].”
BackgroundAge-Related Changes in Skeletal Muscle Oxygen Utilization
Salvatore, S. S., Zelenski, K. N., & Perkins, R. K. (2022) · Journal of Functional Morphology and Kinesiology · doi:10.3390/jfmk7040087 · Cited by 15
“In support, it has been suggested that there are disparities in the rate of atrophy between muscle fiber types, with type II fibers appearing to be more affected with advancing age [63,64].”
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Wang, K., Wang, X., & Wang, Y. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1509519 · Cited by 18
Low survival rate and muscle fiber-dependent aging effects in the McArdle disease mouse model
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“Aging declines muscle mass, strength, and performance [1], and these physiological changes are known as sarcopenia [2,3], which decreases QoL.”
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“These changes have relevant clinical implications, muscle strength is a strong predictor of slow gait speed, severe mobility limitation, risk of falls and hospitalization and high mortality rate [36].”
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“These data may reflect an impaired force-generating capacity in older adults, attributed to the reduced type II muscle fiber size [22, 46].”
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“It is known that aging causes changes in cellular and molecular processes, including in the satellite cell population, excitation–contraction coupling, myofilament interaction, mitochondrial function and adipocyte infiltration [46], which may explain result found between surface MDF and age.”
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The role of amino acids in skeletal muscle health and sarcopenia: A narrative review
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“53 Clinically, this leads to reduced muscle mass, strength, and power, along with increased risks of falls, hospitalization, and mortality.”
Effects of Resistance Exercise on Older Individuals with Sarcopenia: Sex Differences in Humans
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“Aging of the population is linked to an increase in the prevalence of impairment and disability and is expected to impose a tremendous strain on the healthcare system [5,6].”
BackgroundComposition of Muscle Fiber Types in Rat Rotator Cuff Muscles
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“Skeletal muscle undergoes a fast-to-slow fiber type shift and fiber type specific atrophy from early adulthood to old age (Verdijk et al., 2007; Delbono, 2011; Miljkovic et al., 2015).”
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“On the muscular level, increasing age and immobility lead to alterations in the MyHC isoform distribution, fiber type composition and fiber activation [2, 12, 34].”
BackgroundInfluentialHan, S. Y., Kim, N. H., Kim, D., Kim, Y., Park, Y. K., & Kim, S. M. (2022) · Medicina · doi:10.3390/medicina58121768 · Cited by 10
“The mechanisms of such reduced muscle strength associated with aging include changes in cellular or molecular processes such as decreased concentration or ability to regenerate, the interaction of muscle filaments, decreased mitochondrial function, and increased adipocytes in skeletal muscles [64,65].”
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“Additionally, collateral innervation occurs in MyHC I muscle fibers, leading to agerelated remodeling of motor units (Saini et al., 2013; Miljkovic et al., 2015).”
BackgroundAging exaggerates blood pressure response to ischemic rhythmic handgrip exercise in humans
Hasegawa, D., Hori, A., Okamura, Y., Baba, R., Suijo, K., Mizuno, M., Sugawara, J., Kitatsuji, K., Ogata, H., Toda, K., et al. (2021) · Physiological Reports · doi:10.14814/phy2.15125 · Cited by 10
“However, this may not be avoidable, even if the duration of IHG exercise was the same between the groups, because aging causes the skeletal muscle fibers to change to the oxidative fiber type (Miljkovic et al., 2015); thus, fewer metabolites stimulate thinfiber muscle afferents during exercise (Markel et al.”
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“In contrast, malnutrition, inflammation, and sarcopenia induce a fast-to-slow myofiber type shift [10] through the reduction of type II fibers [1]; however, several reports revealed that type I fibers are also reduced in sarcopenia, where they form MyHC-coexpressing fibers [37].”
BackgroundPathophysiology of Muscle in Pulmonary and Cardiovascular Conditions
Kasawara, K. T., Castellanos, M. M., Hanada, M., & Reid, W. D. (2018) · Cardiopulmonary Physical Therapy Journal · doi:10.1097/cpt.0000000000000096 · Cited by 9
“Furthermore, neural factors can also impair muscle force generation and power production because of reduced central nervous system drive, peripheral nerve dysfunction, and alterations in the neuromuscular junction structure/function.(93) This muscle loss not only decreases strength but also compromises the elderly’s b…”
BackgroundNg, Z. Q., Cohen, R., Misur, P., & Weber, D. (2022) · ANZ Journal of Surgery · doi:10.1111/ans.17641 · Cited by 9
“It is not influenced by the acute derangement in physiology during critical illness and thus represents premorbid physiology.(24) Additionally, diagnosis is made opportunistically using cross-sectional imaging that would otherwise usually be acquired as part of routine workup prior to EL.”
BackgroundAkkermansia muciniphila Alleviates Sarcopenia in Senescence-Accelerated Mouse-Prone 8 Mice
Park, S., Kim, H. S., Choi, P. G., Jeong, M. S., Huh, Y. H., Ahn, J., & Jung, C. H. (2025) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2507.07001 · Cited by 9
“The composition of muscle fiber type can change due to various stressors, and during aging, the composition of muscle fibers shifts with relative increase in type 1 and decrease in type 2 muscle fibers [31].”
Kelly, C. R., Mourtzakis, M., Furberg, H. F., Tandon, P., & Paris, M. T. (2021) · Academic Radiology · doi:10.1016/j.acra.2021.06.005 · Cited by 8
Long-Term Recreational Football Training and Health in Aging
Imperlini, E., Mancini, A., Orrù, S., Vitucci, D., Onofrio, V. D., Gallé, F., Valerio, G., Salvatore, G., Liguori, G., Buono, P., et al. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17062087 · Cited by 11
“In addition, a remodeling of the motor units occurs during aging, resulting in reduced force-generating capacity of skeletal muscle [8,11].”
BackgroundCheour, S., Chéour, C., Bragazzi, N. L., Zou, L., Paravlic, A. H., Slimani, M., & Chéour, F. (2021) · Life · doi:10.3390/life11020121 · Cited by 8
“Muscle size is reduced, and architecture altered in old age [6], with the number of motor units and muscle fibers being significantly decreased [7].”
BackgroundAge‐Associated Dysregulation of Postsynaptic Mitochondria Perturbs Reinnervation Kinetics
Guzman, S. D., Fraczek, P. M., Itsani, K., Furati, E., Juros, D., Kenney, G., Valdez, G., Chakkalakal, J. V., & Aguilar, C. A. (2026) · Aging Cell · doi:10.1111/acel.70355 · Cited by 10
“We also observed a loss of fast-twitch myofiber nuclei (Type IIb and Type IIx) following SNCr in young and old-aged muscles (Figure S2C), which agrees with previous work showing that fast-twitch fibers are more susceptible to denervation and atrophy (Coletti et al. 2022; Miljkovic et al. 2015).”
Gany, S. L. S., Tan, J. K., Chin, K., Hakimi, N. H., Rani, N. A., Ihsan, N., & Makpol, S. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1008908 · Cited by 7
“It has been previously reported that ageing causes the number of satellite cells to decrease (Miljkovic et al., 2015).”
BackgroundSekar, J., & Attaway, A. H. (2023) · Glycobiology · doi:10.1093/glycob/cwad081 · Cited by 10
Morphometric and Molecular Muscle Remodeling after Passive Stretching in Elderly Female Rats
Martins, H. R. F., Zotz, T. G. G., Messa, S. P., Capriglione, L. G. A., Zotz, R., de Noronha, L., de Azevedo, M. L. V., & Gomes, A. R. S. (2020) · Clinics · doi:10.6061/clinics/2020/e1769 · Cited by 7
“Fat, connective tissue infiltration, and decline in muscle mass, muscle-fiber cross-sectional area (MFCSA), and myofilament elasticity can be observed (10).”
BackgroundErkoyun, E. (2020) · Turkish Journal of Physical Medicine and Rehabilitation · doi:10.5606/tftrd.2020.3231 · Cited by 7
“The prevalence of sarcopenia ranges from 4 to 27%.[4] In the literature, low gait speed (LGS) and low grip strength (LGrS) are both good predictors of adverse health outcomes.”
BackgroundPredominant Neck Extensor Muscle Weakness: A Rare Manifestation of Idiopathic Polymyositis
Kesserwani, H. N. (2020) · Cureus · doi:10.7759/cureus.8735 · Cited by 7
“The fast twitch fibers are fatiguable and when diseased are prone to immune attack due release of DAMPs and inefficient clearing pathways such as NF-kB and TLRs [15,16].”
BackgroundACTN3 Genotypes and Their Relationship with Muscle Mass and Function of Kosovan Adults
Boshnjaku, A., Krasniqi, E., Tschan, H., & Wessner, B. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18179135 · Cited by 7
“Many changes underlying the age-associated decay of the musculoskeletal system can be understood at the cellular and molecular level [5].”
BackgroundLeite, N., Tadiotto, M. C., de Moraes-Junior, F. B., de Menezes-Junior, F. J., Corazza, P. R. P., da Silva, L. R., Lopes, W. A., de Matos, O., Radominski, R. B., & Coelho-e-Silva, M. J. (2024) · Scientific Reports · doi:10.1038/s41598-024-61805-w · Cited by 9
Zuo, X., Bai, H., Zhao, Q., Zhang, S., Zhao, X., & Feng, X. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04455-3 · Cited by 6
“This aging process also impacts muscle tissue, leading to a reduction in the number of muscle fibers and the capacity to build muscles [10, 11].”
Gittemeier, E. M., Ericson, T., Ghosh, P., Copp, S. W., Opoku‐Acheampong, A. B., & Behnke, B. J. (2017) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3541-0 · Cited by 6
Nunes, J. P., Marcori, A. J., Tomeleri, C. M., do Nascimento, M. A., Mayhew, J. L., Ribeiro, A. S., & Cyrino, E. S. (2019) · International journal of exercise science · doi:10.70252/nncj3157 · Cited by 6
Sassonker, K., Magnezi, R., & Moran, D. S. (2023) · Journal of Bodywork and Movement Therapies · doi:10.1016/j.jbmt.2023.07.014 · Cited by 6
Abnormalities in the genioglossus muscle and its neuromuscular synapse in leptin-deficient male mice
Medharametla, S., Borger, G., Gaonkar, S., & y Valenzuela, I. M.-P. (2025) · Skeletal Muscle · doi:10.1186/s13395-025-00387-1 · Cited by 5
Cogliati, M., Cudicio, A., Benedini, M., Cabral, H. V., Negro, F., Reggiani, C., & Orizio, C. (2023) · European Journal of Applied Physiology · doi:10.1007/s00421-023-05198-0 · Cited by 5
“Given the prevalence of slow fibers in aged tibialis anterior (Orizio et al. 2016; von Haehling et al. 2010; Miljkovic et al. 2015), this can explain the longer delay of mechanical decay in old vs young.”
BackgroundWhey protein and vitamin D supplementation in institutionalized older adults: A randomized trial
Colonetti, T., Grande, A. J., da Rocha, F. R., Dondossola, E. R., Tuon, L., Teles, H. G. B., Bom, B. M., Colonetti, L., & da Rosa, M. I. (2021) · Nutrition and Health · doi:10.1177/02601060211060665 · Cited by 5
“Email: tamycolonetti@hotmail.com number and response of satellite cells, whose function is to maintain skeletal muscle homeostasis and its regeneration (Miljkovic et al., 2015, Nilwik et al., 2013).”
BackgroundFormiga, M. F., Dosbaba, F., Hartman, M., Baťalík, L., Senkyr, V., Radkovcova, I., Richter, S., Brat, K., & Cahalin, L. P. (2023) · Physical Therapy · doi:10.1093/ptj/pzad051 · Cited by 6
Muscle fibre size and myonuclear positioning in trained and aged humans
Battey, E., Levy, Y., Pollock, R. D., Pugh, J. N., Close, G. L., Kalakoutis, M., Lazarus, N. R., Harridge, S. D. R., Ochala, J., & Stroud, M. J. (2024) · Experimental Physiology · doi:10.1113/ep091567 · Cited by 4
“…in skeletal muscle biology is to separate the effects of ageing from the negative effects of lifestyle factors that impact the ageing process (Distefano & Goodpaster, 2018; Lazarus & Harridge, 2017; Miljkovic et al., 2015), with one of the most documented being a lack of physical activity/exercise.”
BackgroundOlstad, O. K., Gautvik, V. T., LeBlanc, M., Kvernevik, K. J., Utheim, T. P., Runningen, A., Wiig, H., Kirkegaard, C., Raastad, T., Reppe, S., et al. (2020) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x20929443 · Cited by 5
Özçakar, L., Ata, A. M., Quittan, M., & Michail, X. (2018) · International Journal of Rehabilitation Research · doi:10.1097/mrr.0000000000000279 · Cited by 5
“Eventually, decrease in muscle size and number of type II fibers; fast to slow fiber transformation; reduction in the number of mitochondria, satellite cells, and myofilaments; excitation-contraction coupling disruption; and (infiltration or) increased amount of adipocytes are seen (Miljkovic et al., 2015).”
BackgroundImpact of Physical Activity Level on Whole-Body and Muscle-Cell Function in Older Adults
Yeo, H., & Lim, J. (2025) · Annals of Geriatric Medicine and Research · doi:10.4235/agmr.24.0141 · Cited by 4
“42) Previous studies have reported that the age-related changes in muscle function at the muscle cellular level 43,44) can be improved through exercise interventions.”
Zhang, B., Wang, S., Wang, Y., Chen, L., & Zhang, H. (2025) · Histochemistry and Cell Biology · doi:10.1007/s00418-025-02414-0 · Cited by 4
“For instance, resistance exercise is well known to promote muscle hypertrophy and strength, whereas aging leads to denervation and atrophy of muscle fibers, resulting in reduced muscle mass and function (Feng et al. 2024; Miljkovic et al. 2015).”
Association between peripheral nerve function and structure in human diabetic nerves
Borire, A. A., Issar, T., Kwai, N. C. G., & Krishnan, A. V. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2017-316074 · Cited by 4
Slo1 deficiency impaired skeletal muscle regeneration and slow‐twitch fibre formation
Xia, C., Wang, Y., Jiang, T., Hu, Y., Yang, C., Ma, X., Zhang, X., & Gao, Y. (2023) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13253 · Cited by 4
Kadota, Y., Yamanokuchi, R., Ohnishi, N., Matsuoka, M., Kawakami, T., Sato, M., & Suzuki, S. (2023) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b23-00165 · Cited by 4
Mitochondrial transfer and implications for muscle function in idiopathic inflammatory myopathies
González-Chapa, J. A., Macêdo, M. B., Naddaf, E., Saketkoo, L. A., & Lood, C. (2023) · Clinical and Experimental Rheumatology · doi:10.55563/clinexprheumatol/5lfq5x · Cited by 4
Translational Significance of the LINE-1 Jumping Gene in Skeletal Muscle
Romero, M. A., Mumford, P. W., Roberson, P. A., Osburn, S. C., Young, K. C., Sedivy, J. M., & Roberts, M. D. (2022) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000301 · Cited by 4
“Skeletal muscle aging in rodents and humans is largely conserved, and there are a number of associated phenotypes including: i) a reduction in fiber size and number of type II fibers, ii) a loss in resident satellite cell proliferative capacity and number, iii) a dysfunction in translational machinery, iv) a decrease…”
BackgroundThe Functional and Anatomical Impacts of Healthy Muscle Ageing
Charles, J. P., & Bates, K. T. (2023) · Biology · doi:10.3390/biology12101357 · Cited by 5
“These differences, while not surprising, support previous work that has shown significant intramuscular fat infiltrations [31] and overall shifts towards a higher relative abundance of slower, type I muscle fibres [32–34] associated with muscle atrophy.”
ResultHunt, N. L., Robinett, M. V., & Brown, T. N. (2024) · Clinical Biomechanics · doi:10.1016/j.clinbiomech.2024.106331 · Cited by 3
Hibernation as a model for skeletal muscle preservation
Porczak, A. E., & Feng, N. Y. (2025) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.15389 · Cited by 3
Li, Z., Huang, X., Chung, R. C. K., Leung, K. L., & Fu, S. N. (2025) · BMC Geriatrics · doi:10.1186/s12877-025-06657-3 · Cited by 3
“Aging causes a range of changes in skeletal muscles, including decreased muscle strength, reduced muscle mass, fast-to-slow fiber type shift, altered muscle architecture and metabolism, and impaired neuromuscular control [1–4].”
The role of immersive virtual reality in geriatric rehabilitation
Aldardour, A. M., & Alnammaneh, S. (2025) · Rehabilitación · doi:10.1016/j.rh.2025.100930 · Cited by 3
Denny, D., Low, D. C., & Gibson, O. R. (2025) · Experimental Physiology · doi:10.1113/ep092690 · Cited by 3
Toda, K. (2016) · Integrative Molecular Medicine · doi:10.15761/imm.1000215 · Cited by 3
He, L., Roie, E. V., Bogaerts, A., Verschueren, S., Delecluse, C., Morse, C., & Thomis, M. (2020) · Genes · doi:10.3390/genes11090968 · Cited by 2
“To some extent, the detraining period in older adults can also be regarded as an ageing process and therefore, some ageing muscle-related mechanisms, such as myofibre denervation [16], atrophy of type II myofibres [17], decreased mitochondrial enzyme activity [18] and reduced synthesis rates of myosin heavy chain [19]…”
Background
Metadata
- Authors
- Miljkovic, N., Lim, J.-Y., Miljkovic, I., & Frontera, W. R.
- Affiliations
- Vanderbilt University (US)
- Seoul National University (KR)
- University of Pittsburgh (US)
- University of Puerto Rico, Medical Sciences Campus (PR)
- Corresponding author
- Frontera, Walter R.
- Venue
- Annals of Rehabilitation Medicine
- Published
- 2015
- Volume
- 39
- Issue
- 2
- Pages
- 155
- ISSN
- 2234-0645 (ISSN-L)
- 2234-0653
- PMC
- PMC4414960
- OpenAlex
- W2049942632
- Cited by
- 309
- References
- 58
- Citations by year
- 2026: 21 · 2025: 20 · 2024: 32 · 2023: 30 · 2022: 24 · 2021: 42 · 2020: 44 · 2019: 28 · 2018: 30 · 2017: 14 · 2016: 23 · 2015: 1
- FWCI
- 2.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Rehabilitation Medicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology (medical) › Nutrition and Health in Aging
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Keywords
- skeletal muscle aging, sarcopenia, muscle fiber atrophy, muscle fiber activation, excitation-contraction coupling, actin-myosin cross-bridges, muscle energy metabolism, muscle regeneration, muscle architecture, functional capacity decline, exercise training intervention
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