This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. NASA's Critical Path Roadmap identifies loss of skeletal muscle function as a key concern for long-term missions to the International Space Station, the Moon, and Mars. Gravitational unloading causes weakness of antigravity muscles due to loss of muscle mass (atrophy) and contractile dysfunction. In selected conditions, especially extravehicular activity (EVA), crewmember performance can also be limited by muscle fatigue. Ground-based studies suggest that oxidative stress contributes to loss of muscle function in both conditions, unloading and strenuous exercise, and that antioxidant pretreatment can protect muscle function. This experimental model is the basis for our current project. Experiments will evaluate a pharmacologic agent that has the potential to oppose oxidative stress in skeletal muscle and protect against muscle fatigue in flight crews. The experimental approach is explicitly pragmatic, designed to identify and develop countermeasures for human testing in the near-to-mid term. The efficacy of the compound tested in this project is supported by preliminary data from animal studies and human trials and is currently approved for systemic administration to humans.
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