Researchers found a key regulator of the oxidative stress response that affects muscle formation during space flight

Muscle atrophy or weakness is a common feature of disease and aging. It can also occur after long periods of inactivity, such as during space flight, when astronauts don’t need to use their muscles as much as they do on Earth to support weight or move. When muscles atrophy in space, they not only decrease in size, but also tend to lose a type of fiber called a “slow twitch” and gain more fiber called a “fast twitch.” “This switch from slow to fast muscle fibers is closely associated with increased oxidative stress,” explains Professor Satoru Takahashi, senior author of the study. “Thus, we speculated that removing factors that protect against oxidative stress would accelerate muscle atrophy under microgravity conditions.”

To explore this, the researchers removed the gene encoding NRF2, which helps control the body’s response to oxidative stress, in mice. Then the mice were sent to stay on the International Space Station for a month. When the mice returned, the researchers compared their calf muscles to those of mice that had spent the same month on the ground. Given this newly discovered role of NFR2, finding treatments that target this protein may be useful to help prevent muscle changes in astronauts during space flight. Targeting NFR2 could also be a promising way to combat muscle wasting in diseases such as cancer or during the aging process.

“Our findings suggest that NFR2 alters skeletal muscle composition during space flight by regulating oxidative and metabolic responses,” said Professor Takahashi. The article, “Factor 2 deficiency associated with nuclear factor E2 (NRF2) accelerates rapid fiber-type transmission in the soleus muscle during space flight,” was published in the Journal of Communications Biology.

In addition to these changes in muscle composition, there are also important changes in the way muscle tissue uses energy and nutrients. This shift in energy metabolism is a common feature of fiber type transmission. “We were surprised to find that the Nrf2 mice did not lose more muscle mass than the control mice in the microgravity environment,” said Professor Takahashi. “However, they did show a significantly accelerated rate of transition from slow to fast fiber types.”

Story Source: This work was supported by a Japan Aerospace Exploration Agency grant (14YPTK-005512; ST), and a scientific research assistance grant in innovative fields from MEXT (18H04965; ST). The authors declare no conflict of interest.

Materials provided by Tsukuba University. Note: Content can be modified according to style and length.

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