Hormonal
Mechanical unloading (disuse) induces skeletal muscle atrophy primarily through a dual mechanism: suppression of the IGF-1-Akt-mTOR protein synthesis pathway and upregulation of the ubiquitin-proteasome system (specifically MuRF1/MAFbx E3 ligases) driven by FOXO transcription factors.
If you are experiencing forced inactivity (like casting or bed rest), your muscles will shrink due to suppressed growth signals (mTOR) and increased breakdown signals (FOXO/MuRF1). While you cannot fully stop this, engaging in any available resistance exercise (even isometric) or ensuring adequate protein intake may help mitigate the rate of loss by keeping these pathways partially active.
It is commonly believed that a disproportion in the rate of protein synthesis and protein degradation is the main cause of muscle loss... decreased activation of the Akt-mTOR pathway is involved in the mechanisms of the attenuated protein synthesis under disuse conditions... the ubiquitin proteasome system is often considered as the most important proteolytic system during disuse conditions that promotes muscle wasting... FOXO transcription factors... have been stated as the major transcription factors regulating both the MuRF1 and MAFbx expressions.
Why this rating
Based on a comprehensive review of multiple human and animal studies, though human molecular data is noted as inconsistent in some areas.
Source
Muscle Atrophy Induced by Mechanical Unloading: Mechanisms and Potential Countermeasures
Yunfang Gao et al. · Frontiers in Physiology · 2018
DOI 10.3389/fphys.2018.00235
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