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New Pharmacological Interventions For Space And Disuse Atrophy

  • 5/14/2018 8:30:00 AM
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New Pharmacological Interventions For Space And Disuse Atrophy

Patrick Ryan, M.S.

Physical inactivity, whether due to sedentary lifestyle or bedrest while recovering from injury or illness, is a significant detriment to overall health. In the short term, reducing activity results in muscle atrophy: the loss of both muscle size and strength. This problem not only applies to athletes who may be forced to reduce activity due to an orthopedic injury, or adults living a sedentary lifestyle, but is also a huge concern in regards to manned spaceflight.

In low Earth orbit and beyond, the force of gravity is severely reduced, putting less demand upon the muscle. This condition is known as microgravity: due to the reduced gravitational force, muscles need to contract less forcefully to perform similar tasks. However, since muscle is a highly dynamic tissue, capable of responding to changes in loading and nutrition, this reduced demand can be quite harmful to the astronaut. Because the muscles do not need to contract as forcefully in microgravity, the body responds by reducing the overall amount of muscle tissue. This occurs because muscle tissue is very metabolically expensive; simply put, keeping muscles requires lots of energy. As the body wants to conserve energy as much as possible, it gets rid of any perceived excess expensive muscle. (2)

Whether when returning to Earth, taking new steps on the lunar surface, or making the first manned Martian expedition, crew members will need strength and durability to complete their mission. Thus, the reductions in muscle strength due to atrophy are significant barriers to manned space exploration. While much research has been conducted in the field, there is not yet a satisfactory answer as to how to prevent microgravity induced muscular atrophy, as current exercise and dietary interventions have fallen short. The Redox Biology and Cell Signaling Lab at Texas A&M University investigates the problem of muscle atrophy on the cellular level, using animal models and advanced analytical techniques to understand the molecular basis of skeletal muscle loss. Among others, we have identified the production of reactive oxygen species (ROS) as a culprit in muscle atrophy and have shown that reducing the presence of these molecules results in protection of the muscle. (1) Specifically, we have investigated the role of a cell membrane bound enzyme, the NADPH Oxidase 2 (NOX2) in atrophic signaling pathways.

Utilizing an animal model of spaceflight, we have gathered data that suggests inhibiting the NOX2 enzyme reduces muscle atrophy, while also preventing several other key cellular events that occur during atrophic signaling in an animal model of muscle disuse. By using advanced microscopic imaging techniques, we can not only measure the size of the muscle fibers but can actually visualize the location of specific molecules involved in atrophy. Our research suggests that NOX2 inhibition with a drug known as gp91ds-tat is protective against atrophy, possibly providing a target for reducing muscle wasting in microgravity, as well as a technique to help terrestrial patients who are bed-ridden or otherwise incapable of physical activity. 



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