Comparative Analysis of Muscle Atrophy During Spaceflight, Nutritional Deficiency and Disuse in the Nematode Caenorhabditis elegans

Author:

Kim Ban-seok1ORCID,Alcantara Alfredo V.1ORCID,Moon Je-Hyun1,Higashitani Atsushi2ORCID,Higashitani Nahoko2,Etheridge Timothy3,Szewczyk Nathaniel J.4ORCID,Deane Colleen S.35ORCID,Gaffney Christopher J.6ORCID,Higashibata Akira7,Hashizume Toko8,Yoon Kyoung-hye9ORCID,Lee Jin I.1ORCID

Affiliation:

1. Division of Biological Science and Technology, College of Science and Technology, Yonsei University, Wonju 26493, Republic of Korea

2. Graduate School of Life Sciences, Tohoku University, Sendai 980-8577, Japan

3. Department of Sport and Health Sciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX1 2LU, UK

4. Ohio Musculoskeletal and Neurological Institute, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH 45701, USA

5. Human Development & Health Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK

6. Lancaster Medical School, Health Innovation One, Sir John Fisher Drive, Lancaster University, Lancaster LA1 4AT, UK

7. Human Spaceflight Technology Directorate, Japan Aerospace Exploration Agency, Tsukuba 305-0047, Japan

8. Advanced Engineering Services Co., Ltd., Tsukuba 305-0032, Japan

9. Department of Physiology, Mitohormesis Research Center, Yonsei University Wonju College of Medicine, Wonju 26426, Republic of Korea

Abstract

While spaceflight is becoming more common than before, the hazards spaceflight and space microgravity pose to the human body remain relatively unexplored. Astronauts experience muscle atrophy after spaceflight, but the exact reasons for this and solutions are unknown. Here, we take advantage of the nematode C. elegans to understand the effects of space microgravity on worm body wall muscle. We found that space microgravity induces muscle atrophy in C. elegans from two independent spaceflight missions. As a comparison to spaceflight-induced muscle atrophy, we assessed the effects of acute nutritional deprivation and muscle disuse on C. elegans muscle cells. We found that these two factors also induce muscle atrophy in the nematode. Finally, we identified clp-4, which encodes a calpain protease that promotes muscle atrophy. Mutants of clp-4 suppress starvation-induced muscle atrophy. Such comparative analyses of different factors causing muscle atrophy in C. elegans could provide a way to identify novel genetic factors regulating space microgravity-induced muscle atrophy.

Funder

National Research Foundation of Korea

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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