Findings from recent studies by the Japan Aerospace Exploration Agency examining musculoskeletal atrophy in space and on Earth

Abstract

The musculoskeletal system provides the body with correct posture, support, stability, and mobility. It is composed of the bones, muscles, cartilage, tendons, ligaments, joints, and other connective tissues. Without effective countermeasures, prolonged spaceflight under microgravity results in marked muscle and bone atrophy. The molecular and physiological mechanisms of this atrophy under unloaded conditions are gradually being revealed through spaceflight experiments conducted by the Japan Aerospace Exploration Agency using a variety of model organisms, including both aquatic and terrestrial animals, and terrestrial experiments conducted under the Living in Space project of the Japan Ministry of Education, Culture, Sports, Science, and Technology. Increasing our knowledge in this field will lead not only to an understanding of how to prevent muscle and bone atrophy in humans undergoing long-term space voyages but also to an understanding of countermeasures against age-related locomotive syndrome in the elderly.

Fig. 1. Recent JAXA space missions in Kibo of ISS.

a Cell culture system used in the Myo Lab project. L6 rat myoblasts at 100% confluence in a disposable cultivation chamber (DCC) were fused by changing the medium to a differentiation medium (i.e., Dulbecco’s modified Eagle’s medium containing 0.5% fetal bovine serum). (Photo by Nikawa, T) b C. elegans culture system used in the CERISE project^–. Upon reaching microgravity at KIBO, flight crews activated the experiments by removing the U-pin. Holder was set into Meas Exp Unit A and transferred into the Cell Biology Experiment Facility (CBEF) with or without 1-g  rotation for either 4 or 8 days. (Photo by Higashitani, A). c Appearance of medaka reared during spaceflight. Medaka was filmed for abnormal behavior to examine physiological changes under microgravity. The recordings showed that the fish became accustomed to life under microgravity but displayed unique behavior such as swimming upside-down (red arrow). Scale bar, 10 mm. d Medaka chamber for live imaging used on the ISS. Twelve larvae at stage 39 can be kept in each “Medaka Chamber”, in which the larvae are placed in Mebiol Gel (Mebiol Inc., Kanagawa, Japan) and then covered with a gas-permeable membrane. The chamber shown was carried aboard Soyuz flight progress M-22M (54 P) (Roscosmos, Russia) in 2014. After arrival at the Japanese Experiment Module of the ISS, the chambers were set under a fluorescence microscope for live imaging for 8 days. The red dotted area indicates an enlarged view (inset) showing three larvae. Scale bar, 10 mm.

Fig. 2. Mice in space.

a A still image captured from a video recording of a C57BL/6J male mouse in microgravity in the ISS. b A still image captured from a video recording of a C57BL/6J male mouse under artificial 1 g conditions generated by a short-arm centrifuge in the ISS. These mice were housed in the mouse habitat cage unit for 35 days and these images were taken on day 5.

Fig. 3. Japanese astronaut Satoshi Furukawa exercising on the T2 treadmill, the Cycle Ergometer with Vibration Isolation and Stabilization System (CEVIS), and the Advanced Resistive Exercise Device (ARED) in the ISS.

Astronauts have daily exercise sessions, which are part of operational tasks onboard the ISS, to minimize muscle atrophy and bone loss risks. The first author and an astronaut S.F. agreed and gave written consent to use these photographs. a T2 treadmill, (b) CEVIS, and (c) ARED.

Fig. 4. Musculoskeletal atrophy and its countermeasures in space.

Key pathways to prevent bone and muscle deterioration in the space environment are represented. Yellow arrows indicate the molecules whose expression changes have been studied in space experiments. Asterisks indicate ground-based experiments and candidates for future space experiments. Question marks indicate candidates for future ground and space research.