{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:48:00Z","timestamp":1784641680013,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007886","name":"Fondation Nestl\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007886","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":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mitochondrial dysfunction has been implicated in sarcopenia. <jats:sup>31<\/jats:sup>P magnetic resonance spectroscopy (MRS) enables non\u2010invasive measurement of adenosine triphosphate (ATP) synthesis rates to probe mitochondrial function. Here, we assessed muscle energetics in older sarcopenic and non\u2010sarcopenic men and compared with muscle biopsy\u2010derived markers of mitochondrial function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Twenty Chinese men with sarcopenia (SARC, age\u00a0=\u00a073.1\u00a0\u00b1\u00a04.1\u00a0years) and 19 healthy aged and sex\u2010matched controls (CON, age\u00a0=\u00a070.3\u00a0\u00b1\u00a04.2\u00a0years) underwent assessment of strength, physical performance, and magnetic resonance imaging. Concentrations of phosphocreatine (PCr), ATP and inorganic phosphate (Pi) as well as muscle pH were measured at rest and during an interleaved rest\u2013exercise protocol to probe muscle mitochondrial function. Results were compared to biopsy\u2010derived mitochondrial complex activity and expression to understand underlying metabolic perturbations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Despite matched muscle contractile power (strength\/cross\u2010sectional area), the ATP contractile cost was higher in SARC compared with CON (low\u2010intensity exercise: 1.06\u00a0\u00b1\u00a00.59 vs. 0.57\u00a0\u00b1\u00a00.22, moderate: 0.93\u00a0\u00b1\u00a00.43 vs. 0.58\u00a0\u00b1\u00a00.68, high: 0.70\u00a0\u00b1\u00a00.57 vs. 0.43\u00a0\u00b1\u00a00.51\u00a0mmol\u00a0L<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>\u00a0bar<jats:sup>\u22121<\/jats:sup>\u00a0cm<jats:sup>\u22122<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.003, &lt;0.0001 and &lt;0.0001, respectively). Post\u2010exercise mitochondrial oxidative synthesis rates (a marker of mitochondrial function) tended to be longer in SARC but did not reach significance (17.3\u00a0\u00b1\u00a06.4 vs. 14.6\u00a0\u00b1\u00a06.5\u00a0mmol\u00a0L<jats:sup>\u22121<\/jats:sup>\u00a0min<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.2). However, relative increases in end\u2010exercise ADP in SARC (31.8\u00a0\u00b1\u00a09.9 vs. 24.0\u00a0\u00b1\u00a07.3\u00a0mmol\u00a0L<jats:sup>\u22121<\/jats:sup>, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.008) may have been a compensatory mechanism. Mitochondrial complex activity was found to be associated with exercise\u2010induced drops in PCr [citrate synthetase activity (CS), Spearman correlation rho\u00a0=\u00a0\u22120.42, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03] and end\u2010exercise ADP (complex III, rho\u00a0=\u00a0\u22120.52, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.01; CS rho\u00a0=\u00a0\u22120.45, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02; SDH rho\u00a0=\u00a0\u22120.45, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03), with CS also being strongly associated with the PCr recovery rate following low intensity exercise (rho\u00a0=\u00a0\u22120.47, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02), and the cost of contraction at high intensity (rho\u00a0=\u00a0\u22120.54, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02). Interestingly, at high intensity, the fractional contribution of oxidative phosphorylation to exercise was correlated with activity in complex II (rho\u00a0=\u00a00.5, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03), CS (rho\u00a0=\u00a00.47, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.02) and SDH (rho\u00a0=\u00a00.46, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03), linking increased mitochondrial complex activity with increased ability to generate energy through oxidative pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study used <jats:sup>31<\/jats:sup>P MRS to assess ATP utilization and resynthesis in sarcopenic muscle and demonstrated abnormal increases in the energy cost during exercise and perturbed mitochondrial energetics in recovery. Associations between mitochondrial complex activity and the fractional contribution to energy requirement during exercise indicate increased ability to generate energy oxidatively in those with better mitochondrial complex activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13220","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T05:41:55Z","timestamp":1683265315000},"page":"1482-1494","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Evidence for inefficient contraction and abnormal mitochondrial activity in sarcopenia using magnetic resonance spectroscopy"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4277-4325","authenticated-orcid":false,"given":"Mary C.","family":"Stephenson","sequence":"first","affiliation":[{"name":"Centre for Translational Medicine (TMR), Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie X.M.","family":"Ho","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine (TMR), Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"},{"name":"Department of Radiology Sengkang Hospital  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenia","family":"Migliavacca","sequence":"additional","affiliation":[{"name":"Nestl\u00e9 Institute of Health Sciences Nestl\u00e9 Research  EPFL Innovation Park 1015 Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kalimeri","sequence":"additional","affiliation":[{"name":"Centre for Translational Medicine (TMR), Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neerja","family":"Karnani","sequence":"additional","affiliation":[{"name":"Singapore Institute for Clinical Sciences (A*STAR)  Singapore Singapore"},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhasis","family":"Banerji","sequence":"additional","affiliation":[{"name":"Synphne Pte. 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