Targeting Myostatin/Activin A Protects Against Skeletal Muscle And Bone Loss During Spaceflight (Astronomy)

Among the major health challenges for astronauts during prolonged space travel are loss of muscle mass and loss of bone mass. One signaling pathway that plays an important role in maintaining muscle and bone homeostasis is that regulated by the secreted signaling proteins, myostatin (MSTN) and activin A. In the recent study, Emily Lee and colleagues investigated the effects of targeting the signaling pathway mediated by the secreted signaling molecules, myostatin and activin A, in mice sent to the International Space Station.

Mice without the gene for myostatin, a protein that limits muscle growth, retained more bone and muscle mass during spaceflight than normal mice that do carry the gene. The larger of the two mice pictured here has been genetically modified to lack myostatin and, as a result, has larger muscles. (Image: © Se-Jin Lee)

They found that 24 of the 40 mice were normal, eight of them were missing the myostatin gene and eight others were treated with a molecule that suppressed both myostatin and a protein known as activin A, which has similar effects on muscle as myostatin.

Normal mice — those that carried the myostatin gene and received no protein-inhibiting treatments — lost significant muscle and bone mass during the 33 days spent in microgravity. In contrast, mice that were missing the myostatin gene and had a muscle mass about twice that of a regular mouse, largely retained their muscles during spaceflight. 

This graphic shows how effective the treatments were at mitigating the bone loss that mice experience in microgravity, with micro-computed tomography (micro-CT) images of femurs and vertebrae of mice that received or did not receive the treatment, both on Earth and at the International Space Station.  (Image credit: Se-Jin Lee)

Also, systemic inhibition of MSTN/activin A signaling using a soluble form of the activin type IIB receptor (ACVR2B), which can bind each of these ligands, led to dramatic increases in both muscle and bone mass, with effects being comparable in ground and flight mice.

They concluded that targeting this signaling pathway (MSTN/activin A) has significant beneficial effects in protecting against both muscle and bone loss in microgravity, suggesting that this strategy may be effective in preventing or treating muscle and bone loss not only in astronauts on prolonged missions but also in people with disuse atrophy on Earth, such as in older adults or in individuals who are bedridden or wheelchair-bound from illness.

References: Se-Jin Lee, Adam Lehar, Jessica U. Meir, Christina Koch, Andrew Morgan, Lara E. Warren, Renata Rydzik,  Daniel W. Youngstrom, Harshpreet Chandok, Joshy George, Joseph Gogain, Michael Michaud, Thomas A. Stoklasek, Yewei Liu, and  Emily L. Germain-Lee, “Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight”, PNAS, 2020, doi: https://doi.org/10.1073/pnas.2014716117

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