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Molecular insights into human soleus muscle atrophy development: long-term dry immersion effects on the
Roman O Bokov1, Kristina A Sharlo1, Natalia A Vilchinskaya1
1Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia.
Abstract:
Muscle disuse results in complex signaling alterations followed by structural and functional changes, such as atrophy, force decrease, and slow-to-fast fiber-type shift. Little is known about human skeletal muscle signaling alterations under long-term muscle disuse. In this study, we describe the effects of 21-day dry immersion on human postural soleus muscle. We performed both transcriptomic analysis and Western blots to describe the states of the key signaling pathways regulating soleus muscle fiber size, fiber type, and metabolism. Twenty-one-day dry immersion resulted in both slow-type and fast-type myofibers atrophy, downregulation of rRNA content, and mTOR signaling. Twenty-one-day dry immersion also leads to slow-to-fast fiber-type and gene expression shift, upregulation of p-eEF2, p-CaMKII, p-ACC content and downregulation of NFATc1 nuclear content. It also caused massive gene expression alterations associated with calcium signaling, cytoskeletal parameters, and downregulated mitochondrial signaling (including fusion, fission, and marker of mitochondrial density).NEW & NOTEWORTHY The main findings of our study are as follows: 1) The soleus slow fibers atrophy after 21-day dry immersion (DI) does not exceed that after 7-day DI; 2) The soleus ubiquitin ligases expression after 21-day DI returns to its initial level; 3) The soleus slow fibers atrophy after 21-day DI is accompanied by a mitochondrial apparatus structural markers decrease; 4) The soleus fibers signaling pathways restructuring process during 21-day DI is carried out in a complex manner.
Insights
Long-term muscle disuse via dry immersion causes slow and fast soleus muscle fiber atrophy and alters key signaling pathways. Mitochondrial signaling is downregulated, while calcium signaling and fiber-type shifts occur.
Area of Science:
- Human physiology
- Skeletal muscle biology
- Molecular signaling
Background:
- Muscle disuse leads to atrophy and functional decline.
- Long-term effects on human skeletal muscle signaling are poorly understood.
- Dry immersion is a model for microgravity-induced muscle unloading.
Purpose of the Study:
- To investigate signaling alterations in human soleus muscle after 21-day dry immersion.
- To analyze changes in fiber size, type, and metabolism.
- To identify key molecular pathways affected by prolonged unloading.
Main Methods:
- Transcriptomic analysis of soleus muscle.
- Western blot analysis of signaling proteins.
- Assessment of muscle fiber characteristics.
Main Results:
- 21-day dry immersion caused atrophy in both slow and fast soleus myofibers.
- Downregulation of rRNA content and mTOR signaling observed.
- Shift in gene expression towards slow-to-fast fiber type and altered calcium and mitochondrial signaling.
- Ubiquitin ligase expression returned to baseline levels by 21 days.
Conclusions:
- Prolonged dry immersion induces complex signaling adaptations in human soleus muscle.
- Atrophy of slow fibers plateaus after 7 days but is accompanied by mitochondrial structural changes.
- Significant restructuring of signaling pathways occurs, impacting muscle metabolism and fiber type.
