{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T21:59:49Z","timestamp":1789682389202,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23CDA1046498"],"award-info":[{"award-number":["23CDA1046498"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL105826"],"award-info":[{"award-number":["R01HL105826"]}],"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":["R01AR078001"],"award-info":[{"award-number":["R01AR078001"]}],"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":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Skeletal muscle plays a vital role in voluntary movement and locomotion. Fast\u2010twitch muscle fibres are characterized by their rapid contraction kinetics, high\u2010force generation and a distinct gene expression profile compared to slow\u2010twitch fibres. These fibres have a predominant expression of fast skeletal myosin binding protein\u2010C (fMyBP\u2010C). The role of fMyBP\u2010C in skeletal muscle disease and aging remains poorly understood. To address this, our study employs mouse models with fMyBP\u2010C ablation to investigate its significance in skeletal muscle physiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Skeletal muscle samples from wild\u2010type, db\/db, MDX and ECC injury model (2\u20137\u2009months) were analysed to determine the fMyBP\u2010C levels. Next, male\n                      <jats:italic>Mybpc2<\/jats:italic>\n                      knockout (C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice, both young (3\u20135\u2009months) and old (22\u2009months), were utilized to investigate the role of fMyBP\u2010C in aging. The effects of C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and aging on the fibre type, size and number, as well as the overall muscle structure, were evaluated using immunohistochemistry and electron microscopy. In\u00a0vivo and ex\u00a0vivo muscle force generation was assessed to determine the functional impact of C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      and aging. RNA sequencing was conducted to identify the altered molecular pathways causing the muscle dysfunction in young and old C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression of fMyBP\u2010C was reduced (0.25\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) in the fast\u2010twitch muscles of db\/db mice, with a modest compensatory upregulation of slow skeletal MyBP\u2010C (sMyBP\u2010C) (~1.15\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). In MDX mice, fMyBP\u2010C levels remain unchanged, whereas sMyBP\u2010C levels were upregulated (~1.2\u2010fold,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). The fMyBP\u2010C expression was 75% higher in the male skeletal muscles (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) compared to females. Studies in young male C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice revealed a reduction in isometric tetanic force generation by 25% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01) and relaxation rate by 42% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice also had 12.8% fewer type IIb fibres (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), and a 20% reduction in type IIb fibre size (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Similarly, aged male C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice exhibited significant deficits in muscle strength, endurance and survival rate relative to their wild\u2010type counterparts. The aged male C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice displayed a reduced size of type IIa, IIx and IIb muscle fibres compared to aged wild\u2010type mice. RNA sequencing revealed that assembly and trimerization of collagen fibril pathway\u2010related genes were altered in C2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>fMyBP\u2010C is a critical regulator of muscle function and homeostasis in young male fast\u2010twitch muscle fibres. Its absence exacerbates the impact of aging on muscle structure and function. These findings suggest that fMyBP\u2010C could serve as a promising therapeutic target for mitigating muscle wasting associated with aging and disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70106","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:04:33Z","timestamp":1763024673000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Fast Myosin Binding Protein\u2010C Is a Vital Regulator in Young and Aged Fast Skeletal Muscle Homeostasis"],"prefix":"10.1002","volume":"16","author":[{"given":"Akhil","family":"Baby","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiovascular Health and Disease, Department of Internal Medicine University of Cincinnati  Cincinnati OH USA"},{"name":"Department of Genetic Engineering, School of Biotechnology Madurai Kamaraj University  Madurai India"},{"name":"Department of Cellular and Molecular Medicine University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyani","family":"Ananthamohan","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiovascular Health and Disease, Department of Internal Medicine University of Cincinnati  Cincinnati OH USA"},{"name":"Department of Cellular and Molecular Medicine University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenna\u00a0N.","family":"McIntyre","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sankar","family":"Natesan","sequence":"additional","affiliation":[{"name":"Department of Genetic Engineering, School of Biotechnology Madurai Kamaraj University  Madurai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6648-1263","authenticated-orcid":false,"given":"Taejeong","family":"Song","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiovascular Health and Disease, Department of Internal Medicine University of Cincinnati  Cincinnati OH USA"},{"name":"Department of Cellular and Molecular Medicine University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"408","article-title":"Linking Age\u2010Related Changes in Skeletal Muscle Mass and Composition With Metabolism and Disease","volume":"9","author":"Janssen I.","year":"2005","journal-title":"Journal of Nutrition, Health & 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