{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:16:22Z","timestamp":1790838982261,"version":"4.1.0"},"reference-count":188,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T00:00:00Z","timestamp":1714694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["23-75-10048"],"award-info":[{"award-number":["23-75-10048"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Skeletal muscle unloading occurs during a wide range of conditions, from space flight to bed rest. The unloaded muscle undergoes negative functional changes, which include increased fatigue. The mechanisms of unloading-induced fatigue are far from complete understanding and cannot be explained by muscle atrophy only. In this review, we summarize the data concerning unloading-induced fatigue in different muscles and different unloading models and provide several potential mechanisms of unloading-induced fatigue based on recent experimental data. The unloading-induced changes leading to increased fatigue include both neurobiological and intramuscular processes. The development of intramuscular fatigue seems to be mainly contributed by the transformation of soleus muscle fibers from a fatigue-resistant, \u201coxidative\u201c \u201cslow\u201d phenotype to a \u201cfast\u201d \u201cglycolytic\u201c one. This process includes slow-to-fast fiber-type shift and mitochondrial density decline, as well as the disruption of activating signaling interconnections between slow-type myosin expression and mitochondrial biogenesis. A vast pool of relevant literature suggests that these events are triggered by the inactivation of muscle fibers in the early stages of muscle unloading, leading to the accumulation of high-energy phosphates and calcium ions in the myoplasm, as well as NO decrease. Disturbance of these secondary messengers leads to structural changes in muscles that, in turn, cause increased fatigue.<\/jats:p>","DOI":"10.3390\/ijms25094984","type":"journal-article","created":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T03:43:46Z","timestamp":1714707826000},"page":"4984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Disuse-Induced Muscle Fatigue: Facts and Assumptions"],"prefix":"10.3390","volume":"25","author":[{"given":"Xenia V.","family":"Sergeeva","sequence":"first","affiliation":[{"name":"Institute of Biomedical Problems, RAS, Khorosevskoye Shosse, 76a, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina D.","family":"Lvova","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Problems, RAS, Khorosevskoye Shosse, 76a, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5413-6312","authenticated-orcid":false,"given":"Kristina A.","family":"Sharlo","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Problems, RAS, Khorosevskoye Shosse, 76a, 123007 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sharlo, K., Tyganov, S.A., Tomilovskaya, E., Popov, D.V., Saveko, A.A., and Shenkman, B.S. 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