{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:43:25Z","timestamp":1791312205143,"version":"4.3.1"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM125503"],"award-info":[{"award-number":["P20GM125503"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15AR069913\/AR\/NIAMS"],"award-info":[{"award-number":["R15AR069913\/AR\/NIAMS"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Muscle atrophy is a common pathology associated with disuse, such as prolonged bed rest or spaceflight, and is associated with detrimental health outcomes. There is emerging evidence that disuse atrophy may differentially affect males and females. Cellular mechanisms contributing to the development and progression of disuse remain elusive, particularly protein turnover cascades. The purpose of this study was to investigate the initial development and progression of disuse muscle atrophy in male and female mice using the well\u2010established model of hindlimb unloading (HU).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>One hundred C57BL\/6J mice (50 male and 50 female) were hindlimb suspended for 0 (control), 24, 48, 72, or 168\u00a0h to induce disuse atrophy (10 animals per group). At designated time points, animals were euthanized, and tissues (extensor digitorum longus, gastrocnemius, and soleus for mRNA analysis, gastrocnemius and extensor digitorum longus for protein synthesis rates, and tibialis anterior for histology) were collected for analysis of protein turnover mechanisms (protein anabolism and catabolism).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both males and females lost ~30% of tibialis anterior cross\u2010sectional area after 168\u00a0h of disuse. Males had no statistical difference in MHCIIB fibre area, whereas unloaded females had ~33% lower MHCIIB cross\u2010sectional area by 168\u00a0h of unloading. Both males and females had lower fractional protein synthesis rates (FSRs) within 24\u201348\u00a0h of HU, and females appeared to have a greater reduction compared with males within 24\u00a0h of HU (~23% lower FSRs in males vs. 40% lower FSRs in females). Males and females exhibited differential patterns and responses in multiple markers of protein anabolism, catabolism, and myogenic capacity during the development and progression of disuse atrophy. Specifically, females had greater mRNA inductions of catabolic factors\n                      <jats:italic>Ubc<\/jats:italic>\n                      and\n                      <jats:italic>Gadd45a<\/jats:italic>\n                      (~4\u2010fold greater content in females compared with ~2\u2010fold greater content in males) and greater inductions of anabolic inhibitors\n                      <jats:italic>Redd1<\/jats:italic>\n                      and\n                      <jats:italic>Deptor<\/jats:italic>\n                      with disuse across multiple muscle tissues exhibiting different fibre phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest that the aetiology of disuse muscle atrophy is more complicated and nuanced than previously thought, with different responses based on muscle phenotypes and between males and females, with females having greater inductions of atrophic markers early in the development of disuse atrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12693","type":"journal-article","created":{"date-parts":[[2021,3,6]],"date-time":"2021-03-06T01:39:59Z","timestamp":1614994799000},"page":"717-730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Female mice may have exacerbated catabolic signalling response compared to male mice during development and progression of disuse atrophy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3829-1021","authenticated-orcid":false,"given":"Megan E.","family":"Rosa\u2010Caldwell","sequence":"first","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongkyun","family":"Lim","sequence":"additional","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wesley A.","family":"Haynie","sequence":"additional","affiliation":[{"name":"Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob L.","family":"Brown","sequence":"additional","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John William","family":"Deaver","sequence":"additional","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francielly","family":"Morena Da Silva","sequence":"additional","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa T.","family":"Jansen","sequence":"additional","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Lee","sequence":"additional","affiliation":[{"name":"Cachexia Research Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Wiggs","sequence":"additional","affiliation":[{"name":"Integrative Physiology and Nutrition Laboratory Name, Department of Health and Kinesiology University of Texas at Tyler  Tyler TX USA"},{"name":"Department of Health, Human Performance and Recreation Baylor University  Waco TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyrone A.","family":"Washington","sequence":"additional","affiliation":[{"name":"Exercise Muscle Biology Laboratory, Exercise Science Research Center, Department of Health, Human Performance and Recreation University of Arkansas  Fayetteville AR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas 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