Rapid changes in transcriptomic profile and mitochondrial function in human soleus muscle after 3-day dry immersion

Area of Science:

• Exercise Physiology
• Molecular Biology
• Muscle Biology

Background:

• Physical unloading, such as dry immersion, models microgravity effects on skeletal muscle.
• The soleus muscle, with its slow-twitch fibers, is crucial for posture and susceptible to unloading-induced deconditioning.
• Understanding molecular changes during short-term unloading is vital for developing countermeasures.

Purpose of the Study:

• To investigate the impact of 3-day dry immersion on mitochondrial function, transcriptomic, and proteomic profiles in the human soleus muscle.
• To identify molecular targets for preventing muscle deconditioning during physical inactivity.

Main Methods:

• Dry immersion model in six healthy females.
• Assessment of mitochondrial respiration in permeabilized muscle fibers.
• Mass spectrometry-based quantitative proteomics to analyze protein content.
• RNA-sequencing (RNA-seq) to analyze transcriptomic profiles.

Main Results:

• ADP-stimulated respiration in soleus muscle fibers decreased by 25-34% without a reduction in mitochondrial enzyme content, indicating regulatory disruption.
• Dry immersion induced widespread changes in the transcriptomic profile, with downregulated mRNAs linked to mitochondrial function, lipid metabolism, and insulin signaling.
• No significant changes were observed in the content of highly abundant muscle proteins, likely due to their long half-lives.

Conclusions:

• Short-term dry immersion causes significant transcriptomic alterations in the soleus muscle, affecting pathways crucial for energy metabolism and cellular function.
• The reduction in mitochondrial respiration is regulatory rather than due to protein loss.
• Identified downregulated mRNAs may serve as targets for interventions against muscle disuse atrophy.