Astronauts experience a drastic loss of muscle mass, decreased strength, and insulin resistance despite performing daily high-intensity physical exercise that, on Earth, would normally induce muscle growth. Partially mimicking spaceflight, prolonged bed rest causes muscle atrophy, strength loss, and glucose intolerance. To uncover the underlying mechanisms, we employed high-sensitivity single-fiber proteomics to characterize the molecular remodeling induced by disuse and inactivity during bed rest, as well as the changes in the muscle proteome of astronauts before and after a mission aboard the International Space Station.
Muscle focal adhesions—structures involved in fiber–matrix interactions and insulin receptor stabilization—were found to be strongly downregulated both during bed rest and spaceflight, and were restored upon reloading. Antioxidant response pathways were significantly upregulated in slow-twitch muscle fibers but not in fast-twitch ones. Disuse alone led to an increase in markers of neuromuscular damage and in the pathway controlling EIF5A hypusination.
These proteomic signatures of mechanical disuse in different muscle fiber subtypes help distinguish the effects of microgravity from the pleiotropic challenges of spaceflight.
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