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The principal cause of the limited effectiveness of existing exercise countermeasures is the difficulty in achieving full loading forces in space. The implementation of countermeasures which require small devices and simulate Earth\u2010like loading forces to maintain muscle mass, strength and endurance is therefore highly desirable. At present, the cellular mechanisms that induce muscle atrophy in weightlessness are not yet fully known; a better understanding of how skeletal muscle cells adapt to microgravity will help in designing more effective countermeasures to sustain the health and operational capacity of the crew during long\u2010 and short\u2010duration missions. The 6\u00b0 head\u2010down\u2010tilt bed rest is a powerful ground\u2010based analogue platform to simulate and study the physiological effects of spaceflight on the human body, and test the effectiveness of countermeasures before they are potentially applied in space. The aims of this narrative review are therefore to provide an overview of (i) the main mechanisms underlining muscle atrophy learnt from space and bed rest studies, (ii) the currently available countermeasures, and (iii) potential suitable countermeasures \u2013 such as neuromuscular electrical stimulation that is delivered with light and small portable units \u2013 to attenuate muscle wasting in astronauts during spaceflight.<\/jats:p>","DOI":"10.1113\/ep092345","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T01:39:23Z","timestamp":1742261963000},"page":"4179-4194","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Microgravity\u2010induced changes in skeletal muscle and possible countermeasures: What we can learn from bed rest and human space studies"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8651-818X","authenticated-orcid":false,"given":"Alessandra","family":"Bosutti","sequence":"first","affiliation":[{"name":"Department of Life Sciences University of Trieste  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bergita","family":"Ganse","sequence":"additional","affiliation":[{"name":"Departments and Institutes of Surgery Saarland University  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5670-286X","authenticated-orcid":false,"given":"Nicola A.","family":"Maffiuletti","sequence":"additional","affiliation":[{"name":"Human Performance Lab Schulthess Clinic  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3781-5177","authenticated-orcid":false,"given":"Rob C. 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