Signatures of muscle disuse in spaceflight and bed rest revealed by single muscle fiber proteomics

Astronauts experience dramatic loss of muscle mass, decreased strength, and insulin resistance, despite performing daily intense physical exercise that would lead to muscle growth on Earth. Partially mimicking spaceflight, prolonged bed rest causes muscle atrophy, loss of force, and glucose intolerance. To unravel the underlying mechanisms, we employed highly sensitive single fiber proteomics to detail the molecular remodeling caused by unloading and inactivity during bed rest and changes of the muscle proteome of astronauts before and after a mission on the International Space Station. Muscle focal adhesions, involved in fiber-matrix interaction and insulin receptor stabilization, are prominently downregulated in both bed rest and spaceflight and restored upon reloading. Pathways of antioxidant response increased strongly in slow but not in fast muscle fibers. Unloading alone upregulated markers of neuromuscular damage and the pathway controlling EIF5A hypusination. These proteomic signatures of mechanical unloading in muscle fiber subtypes contribute to disentangle the effect of microgravity from the pleiotropic challenges of spaceflight.

Automated summary

Astronauts experience muscle loss, decreased strength, and insulin resistance in space, as well as during prolonged bed rest. By using proteomics, the study reveals molecular remodeling and changes in muscle proteins during bed rest and spaceflight, shedding light on the effects of microgravity and inactivity. Muscle focal adhesions and antioxidant response pathways are downregulated during unloading and restored upon reloading. Additionally, markers of neuromuscular damage are upregulated during unloading.