Proteome-wide Adaptations of Mouse Skeletal Muscles during a Full Month in Space

The
safety of space flight is challenged by a severe loss of skeletal
muscle mass, strength, and endurance that may compromise the health
and performance of astronauts. The molecular mechanisms underpinning
muscle atrophy and decreased performance have been studied mostly
after short duration flights and are still not fully elucidated. By
deciphering the muscle proteome changes elicited in mice after a full
month aboard the BION-M1 biosatellite, we observed that the antigravity
soleus incurred the greatest changes compared with locomotor muscles.
Proteomics data notably suggested mitochondrial dysfunction, metabolic
and fiber type switching toward glycolytic type II fibers, structural
alterations, and calcium signaling-related defects to be the main
causes for decreased muscle performance in flown mice. Alterations
of the protein balance, mTOR pathway, myogenesis, and apoptosis were
expected to contribute to muscle atrophy. Moreover, several signs
reflecting alteration of telomere maintenance, oxidative stress, and
insulin resistance were found as possible additional deleterious effects.
Finally, 8 days of recovery post flight were not sufficient to restore
completely flight-induced changes. Thus in-depth proteomics analysis
unraveled the complex and multifactorial remodeling of skeletal muscle
structure and function during long-term space flight, which should
help define combined sets of countermeasures before, during, and after
the flight.