Targeting myostatin/activin A protects against skeletal muscle and bone loss during spaceflight

Authors: Se‐Jin Lee, Adam Lehar, Jessica U. Meir, Christina Koch, Andrew Morgan, L. E. Warren, Renata Rydzik, Daniel W. Youngstrom, Harshpreet Chandok, Joshy George, Joseph Gogain, Michael Michaud, Thomas A. Stoklasek, Yewei Liu, Emily L. Germain‐Lee - Proceedings of the National Academy of Sciences, PNAS 2020 cited by 115

mice, were largely maintained during spaceflight. 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. Exposure to microgravity and treatment with the soluble receptor each led to alterations in numerous signaling pathways, which were reflected in changes in levels of key signaling components in the blood as well as their RNA expression levels in muscle and bone. These findings have implications for therapeutic strategies to combat the concomitant muscle and bone loss occurring in people afflicted with disuse atrophy on Earth as well as in astronauts in space, especially during prolonged missions.