{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T19:53:32Z","timestamp":1787860412870,"version":"build-2784847793"},"reference-count":62,"publisher":"Portland Press Ltd.","issue":"6","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"name":"National Institute of Aging","award":["RO1AG089307"],"award-info":[{"award-number":["RO1AG089307"]}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The fundamental intracellular mechanisms underlying exercise intolerance and muscle weakness in patients with systemic sclerosis (SSc) are poorly understood. Thus, in six SSc patients (55\u00a0\u00b1\u00a011 yr) and six age-matched healthy controls (50\u00a0\u00b1\u00a013 yr), we assessed both skeletal muscle metabolism and intracellular O2 availability in vivo during submaximal contractions. Specifically, during dynamic plantar flexion exercise at 40% of maximal aerobic power, we used a multimodal approach combining phosphorus (31P) and proton (1H) MRS of deoxymyoglobin to examine both skeletal muscle energy pathways and intracellular partial pressure of O2 (iPO2). Both myoglobin O2 levels (SSc: 70\u00a0\u00b1\u00a07% and controls: 79\u00a0\u00b1\u00a04%; P\u00a0=\u00a00.03;) and end-exercise iPO2 (SSc: 8\u00a0\u00b1\u00a04 mmHg and controls: 17\u00a0\u00b1\u00a08 mmHg; P\u00a0=\u00a00.021; d\u00a0=\u00a01.36) were lower in SSc than healthy controls. The rate of ATP synthesis from oxidative phosphorylation was also lower in SSc than controls (SSc: 5.2\u00a0\u00b1\u00a03.4\u00a0mM min\u22121 and controls: 11.8\u00a0\u00b1\u00a03.6\u00a0mM min\u22121;P\u00a0=\u00a00.015) whereas PCr depletion was augmented (SSc: 55\u00a0\u00b1\u00a015% from resting baseline and controls: 77\u00a0\u00b1\u00a09% from resting baseline; P\u00a0=\u00a00.015). This shift toward a greater reliance on anaerobic metabolism led to an accumulation of inorganic phosphate diprotonated during exercise (SSc: 2.7\u00a0\u00b1\u00a01.2\u00a0mM and controls: 1.4\u00a0\u00b1\u00a00.5\u00a0mM; P\u00a0=\u00a00.037). Together, these findings indicate that critically low iPO2 severely limits oxidative phosphorylation rate even during moderate-intensity dynamic plantar flexion exercise in patients with SSc. The magnitude of the disease-induced shift in metabolism and iPO2 was so extensive that it was greater than the metabolic alterations found in patients suffering from advanced chronic cardiovascular diseases. In addition, the compensatory increase in anaerobic metabolism promoted the accumulation of inorganic phosphate diprotonated, which could amplify the susceptibility to muscle fatigue and mediate premature exercise cessation in patients with SSc.<\/jats:p>","DOI":"10.1042\/cs20250355","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T13:35:20Z","timestamp":1778765720000},"page":"1163-1174","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Compromised muscle energetics and intracellular O2 availability during dynamic contraction in the plantar flexor muscles of patients with systemic sclerosis"],"prefix":"10.1042","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5029-2457","authenticated-orcid":false,"given":"Gwenael","family":"Layec","sequence":"first","affiliation":[{"name":"1School of Health and Kinesiology, University of Nebraska Omaha, NE, U.S.A."},{"name":"2Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy\u00a0M.","family":"Frech","sequence":"additional","affiliation":[{"name":"3Department of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center and Tennessee Valley Healthcare System, Nashville, USA"},{"name":"4Geriatric Research, Education, and Clinical Center, George E. Whalen VA Medical Center, Salt Lake City, Utah, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammet\u00a0Enes","family":"Erol","sequence":"additional","affiliation":[{"name":"1School of Health and Kinesiology, University of Nebraska Omaha, NE, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel\u00a0R.","family":"Machin","sequence":"additional","affiliation":[{"name":"5Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.\u00a0Walter","family":"Wray","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah, U.S.A."},{"name":"4Geriatric Research, Education, and Clinical Center, George E. Whalen VA Medical Center, Salt Lake City, Utah, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u00a0Kee","family":"Jeong","sequence":"additional","affiliation":[{"name":"6Department of Radiology, University of Utah, Salt Lake City, Utah, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony\u00a0J.","family":"Donato","sequence":"additional","affiliation":[{"name":"2Department of Medicine, Division of Geriatrics, University of Utah, Salt Lake City, Utah, U.S.A."},{"name":"4Geriatric Research, Education, and Clinical Center, George E. Whalen VA Medical Center, Salt Lake City, Utah, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"2026060106361016500_B1","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1136\/annrheumdis-2017-211448","article-title":"Mapping and predicting mortality from systemic sclerosis","volume":"76","author":"Elhai","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"2026060106361016500_B2","first-page":"2031","article-title":"Hospital admissions, length of stay, charges, and in-hospital death among patients with systemic sclerosis","volume":"28","author":"Nietert","year":"2001","journal-title":"J. Rheumatol."},{"key":"2026060106361016500_B3","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1136\/ard.2006.066068","article-title":"Changes in causes of death in systemic sclerosis, 1972\u20132002","volume":"66","author":"Steen","year":"2007","journal-title":"Ann. Rheum. 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