{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T23:49:56Z","timestamp":1789516196323,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Duchenne muscular dystrophy (DMD) is characterized by progressive muscle wasting and weakness. Prescribed moderate exercise in patients is beneficial, but concerns remain due to the vulnerability of dystrophic muscle to damage. Voluntary wheel running (VWR) is a self\u2010regulated form of exercise that improves muscle health in the typical C57.mdx mouse model of DMD. The purpose of the current study was to investigate the impact of VWR in more severe and clinically relevant D2.mdx mice. Male D2.mdx animals were assigned to a sedentary (D2.mdx SED) or VWR group for 8\u201310\u00a0weeks, whereas DBA\/2J wild\u2010type mice served as healthy, sedentary controls (WT SED). Selective skeletal muscle mass and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      force generation were elevated in D2.mdx animals that ran a relatively high volume (D2.mdx High VWR; 1.84 \u00b1 0.84 km\/day) compared to low\u2010volume runners (D2.mdx Low VWR; 0.46 \u00b1 0.31 km\/day) and SED counterparts. VWR did not exacerbate the dystrophy, and instead attenuated the fibrotic profile compared to D2.mdx SED mice. A VWR\u2010induced shift towards a more slow, oxidative phenotype was also observed. Mitochondrial respiration was reduced in D2.mdx SED animals\n                      <jats:italic>versus<\/jats:italic>\n                      WT SED mice but was partially restored following both Low and High VWR. Finally, a dose\u2010dependent increase in the expression of mitochondrial proteins was observed following VWR, whereas markers of mitochondrial fusion were particularly elevated in D2.mdx High VWR mice. Our results indicate that VWR enhances muscle and mitochondrial biology in D2.mdx animals and further supports the therapeutic role of exercise for DMD patients.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16677-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Duchenne muscular dystrophy (DMD) is a life\u2010limiting neuromuscular disorder characterized by muscle weakness and wasting. Skeletal and cardiac muscle quality is compromised in the dystrophic condition.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Exercise promotes functional and molecular adaptations in healthy individuals and mild dystrophic mouse models. However, the effects of exercise in more severe and clinically relevant models of DMD require investigation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>A relatively high volume of voluntary wheel running (VWR) augmented selective muscle mass and muscle function without exacerbating the dystrophic pathology in D2.mdx mice.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Volitional exercise normalized dystrophic skeletal muscle mitochondrial respiration and upregulated mitochondrial content compared to sedentary counterparts. A higher dose of VWR increased organelle fusion protein expression compared to both healthy and dystrophic sedentary animals, as well as D2.mdx mice that ran lower volumes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Our results provide evidence from a severe preclinical model that volitional exercise may be a safe and efficacious lifestyle\u2010based intervention for DMD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp286768","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T07:10:43Z","timestamp":1744009843000},"page":"849-867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Volitional exercise elicits physiological and molecular improvements in the severe D2.mdx mouse model of Duchenne muscular dystrophy"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1202-8356","authenticated-orcid":false,"given":"Stephanie R.","family":"Mattina","sequence":"first","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9238-3904","authenticated-orcid":false,"given":"Sean Y.","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8977-2055","authenticated-orcid":false,"given":"Andrew I.","family":"Mikhail","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8772-1905","authenticated-orcid":false,"given":"Derek W.","family":"Stouth","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cora E.","family":"Jornacion","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4732-5473","authenticated-orcid":false,"given":"Irena A.","family":"Rebalka","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4974-4820","authenticated-orcid":false,"given":"Thomas J.","family":"Hawke","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4592-4093","authenticated-orcid":false,"given":"Vladimir","family":"Ljubicic","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University  Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.24451"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2001.90.5.1900"},{"key":"e_1_2_5_4_1","first-page":"1","article-title":"Effectiveness of low\u2010intensity aerobic exercise with assisted bicycle exercises on quality of life and lung functions in Duchenne muscular dystrophy","volume":"22","author":"Anandan D.","year":"2024","journal-title":"Manual Therapy, Posturology & Rehabilitation Journal"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13216"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.108632"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035273"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.049930"},{"issue":"10","key":"e_1_2_5_9_1","first-page":"1","article-title":"ERK1\/2 signaling induces skeletal muscle slow fiber\u2010type switching and reduces muscular dystrophy disease severity","volume":"4","author":"Boyer J. 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