Skeletal Muscle in Health, Exercise and Aging

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 5779

Special Issue Editor


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Guest Editor
Department of Sports Medicine, University Medicine Tübingen, Tübingen, Germany
Interests: skeletal muscle plasticity; molecular mechanisms of exercise adaptation; cachexia and sarcopenia

Special Issue Information

Dear Colleagues,

Skeletal muscle is a highly dynamic tissue that permanently adapts to external stimuli, such as exercise. Neuronal, mechanical, hormonal and metabolic signals induce characteristic changes in muscle morphology and physiology, such as hypertrophy or changes in fiber type distribution.

In recent years, data have suggested that physical activity might also induce long-term epigenetic changes in skeletal muscle, which is called “epigenetic memory”. Thus, prior exercise experience might determine how a person reacts to training, even after a long period of inactivity.

On the other hand, aging and chronic diseases, which are often associated with ongoing, low-grade inflammation, lead to muscle decay, resulting in syndromes such as sarcopenia and cachexia. Decreased skeletal muscle mass is associated with immobility, which, in turn, causes skeletal muscle decay—a vicious circle, Remarkably, regular exercise can slow down the rate of decay, even in chronically ill and elderly subjects, and alternative methods, such as electro-myo-stimulation (EMS), have been developed and are evaluated for those who cannot efficiently exercise.

This Special Issue will focus on multiple mechanisms involved in regulating skeletal muscle plasticity in health and disease.

Research areas may include, but are not limited to, the following topics:

  • Molecular mechanisms of skeletal muscle adaptation to exercise;
  • Different exercise regimens and skeletal muscle plasticity;
  • Exercise and skeletal muscle epigenetic memory;
  • Molecular mechanisms of skeletal muscle decay in cachexia and sarcopenia;
  • Molecular effects of EMS.

Both original and review articles are welcome.

Dr. Barbara Munz
Guest Editor

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Keywords

  • skeletal muscle
  • molecular mechanisms of exercise adaptation
  • aging
  • cachexia
  • sarcopenia

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Published Papers (3 papers)

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Research

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24 pages, 3307 KiB  
Article
A Deficiency in Glutamine-Fructose-6-Phosphate Transaminase 1 (Gfpt1) in Skeletal Muscle Results in Reduced Glycosylation of the Delta Subunit of the Nicotinic Acetylcholine Receptor (AChRδ)
by Stephen Henry Holland, Ricardo Carmona-Martinez, Kaela O’Connor, Daniel O’Neil, Andreas Roos, Sally Spendiff and Hanns Lochmüller
Biomolecules 2024, 14(10), 1252; https://doi.org/10.3390/biom14101252 - 3 Oct 2024
Viewed by 1610
Abstract
The neuromuscular junction (NMJ) is the site where the motor neuron innervates skeletal muscle, enabling muscular contraction. Congenital myasthenic syndromes (CMS) arise when mutations in any of the approximately 35 known causative genes cause impaired neuromuscular transmission at the NMJ, resulting in fatigable [...] Read more.
The neuromuscular junction (NMJ) is the site where the motor neuron innervates skeletal muscle, enabling muscular contraction. Congenital myasthenic syndromes (CMS) arise when mutations in any of the approximately 35 known causative genes cause impaired neuromuscular transmission at the NMJ, resulting in fatigable muscle weakness. A subset of five of these CMS-causative genes are associated with protein glycosylation. Glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) is the rate-limiting enzyme within the hexosamine biosynthetic pathway (HBP), a metabolic pathway that produces the precursors for glycosylation. We hypothesized that deficiency in Gfpt1 expression results in aberrant or reduced glycosylation, impairing the proper assembly and stability of key NMJ-associated proteins. Using both in vitro and in vivo Gfpt1-deficient models, we determined that the acetylcholine receptor delta subunit (AChRδ) has reduced expression and is hypo-glycosylated. Using laser capture microdissection, NMJs were harvested from Gfpt1 knockout mouse muscle. A lower-molecular-weight species of AChRδ was identified at the NMJ that was not detected in controls. Furthermore, Gfpt1-deficient muscle lysates showed impairment in protein O-GlcNAcylation and sialylation, suggesting that multiple glycan chains are impacted. Other key NMJ-associated proteins, in addition to AChRδ, may also be differentially glycosylated in Gfpt1-deficient muscle. Full article
(This article belongs to the Special Issue Skeletal Muscle in Health, Exercise and Aging)
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11 pages, 1160 KiB  
Article
Unmodulated 40 Hz Stimulation as a Therapeutic Strategy for Aging: Improvements in Metabolism, Frailty, and Cognitive Function in Senescence-Accelerated Prone 10 Mice
by Tatsunori Shimizu, Hidetaka Ota, Ayuto Kodama, Yasuhiro Suzuki, Takako Ohnuma, Rieko Suzuki, Kaoru Sugawara, Yasushi Sato and Hiroyuki Kodama
Biomolecules 2024, 14(9), 1079; https://doi.org/10.3390/biom14091079 - 28 Aug 2024
Cited by 1 | Viewed by 2558
Abstract
With aging populations in many countries, including Japan, efforts to mitigate the aging-related decline in physical function have gained importance not only for improving individual quality of life but also for mitigating the effects of this loss of function on society. Impaired glucose [...] Read more.
With aging populations in many countries, including Japan, efforts to mitigate the aging-related decline in physical function have gained importance not only for improving individual quality of life but also for mitigating the effects of this loss of function on society. Impaired glucose tolerance, muscle weakness, and cognitive decline are well-known effects of aging. These interrelated factors can create a vicious cycle because impaired glucose tolerance can accelerate muscle weakness and cognitive decline. Unmodulated 40 Hz (u40Hz) stimulation is imperceptible to the human ear and has been reported to improve cognitive function in humans and mice. However, research on the effects of u40Hz stimulation is still limited. This study aimed to report the effects of u40Hz stimulation on glucose tolerance and muscle strength in senescence-accelerated prone (SAMP)-10 mice, a model of accelerated aging. SAMP-10 mice underwent five weeks of u40Hz stimulation followed by glucose-tolerance tests, cognitive and behavioral assessments, and frailty evaluations. In comparison with the control group, the u40Hz-stimulation group showed mitigation of age-related decline in glucose tolerance, a better frailty index (FI), and notably preserved muscle strength. Microarray analysis of stimulated muscle tissue revealed significant upregulation of β-oxidation genes and genes functioning downstream of peroxisome proliferator-activated receptor gamma, and significant downregulation of clock genes. These findings indicate the beneficial effects of u40Hz stimulation on glucose tolerance, muscle strength, and cognitive function, warranting further research in this area. Full article
(This article belongs to the Special Issue Skeletal Muscle in Health, Exercise and Aging)
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Review

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21 pages, 1582 KiB  
Review
Evolutionary Insights into Irisin/FNDC5: Roles in Aging and Disease from Drosophila to Mammals
by Kiwon Lee and Myungjin Kim
Biomolecules 2025, 15(2), 261; https://doi.org/10.3390/biom15020261 - 11 Feb 2025
Viewed by 926
Abstract
The Irisin/FNDC5 protein family has emerged as a pivotal link between exercise and the prevention of age-associated diseases. Irisin is highly expressed during exercise from skeletal and cardiac muscle cells, playing a critical role in mediating systemic health benefits through its actions on [...] Read more.
The Irisin/FNDC5 protein family has emerged as a pivotal link between exercise and the prevention of age-associated diseases. Irisin is highly expressed during exercise from skeletal and cardiac muscle cells, playing a critical role in mediating systemic health benefits through its actions on various tissues. However, Irisin levels decline with age, correlating with a heightened incidence of diseases such as muscle weakness, cardiovascular disorders, and neurodegeneration. Notably, the administration of Irisin has shown significant potential in both preventing and treating these conditions. Recently, an Irisin/FNDC5 homolog was identified in an invertebrate Drosophila model, providing valuable insights into its conserved role in exercise physiology. Importantly, Irisin/FNDC5 has been demonstrated to regulate autophagy—a process essential for clearing excessive nutrients, toxic aggregates, and dysfunctional organelles—in both flies and mammals. Dysregulated autophagy is often implicated in age-related diseases, highlighting its relevance to Irisin/FNDC5’s functions. These findings deepen our understanding of Irisin/FNDC5’s roles and its potential as a therapeutic target for mitigating aging-related health decline. Further studies are needed to elucidate the precise mechanisms by which Irisin regulates autophagy and its broader impact on physiological aging and related diseases. Full article
(This article belongs to the Special Issue Skeletal Muscle in Health, Exercise and Aging)
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