{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:16:58Z","timestamp":1790198218721,"version":"4.1.0"},"reference-count":58,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T00:00:00Z","timestamp":1711584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG054454"],"award-info":[{"award-number":["R01AG054454"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The favorable health-promoting adaptations to exercise result from cumulative responses to individual bouts of physical activity. Older adults often exhibit anabolic resistance; a phenomenon whereby the anabolic responses to exercise and nutrition are attenuated in skeletal muscle. The mechanisms contributing to age-related anabolic resistance are emerging, but our understanding of how chronological age influences responsiveness to exercise is incomplete. The objective was to determine the effects of healthy aging on peripheral blood metabolomic response to a single bout of resistance exercise and whether any metabolites in circulation are predictive of anabolic response in skeletal muscle.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Thirty young (20\u201335 years) and 49 older (65\u201385 years) men and women were studied in a cross-sectional manner. Participants completed a single bout of resistance exercise consisting of eight sets of 10 repetitions of unilateral knee extension at 70% of one-repetition maximum. Blood samples were collected before exercise, immediately post exercise, and 30-, 90-, and 180-minutes into recovery. Proton nuclear magnetic resonance spectroscopy was used to profile circulating metabolites at all timepoints. Serial muscle biopsies were collected for measuring muscle protein synthesis rates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our analysis revealed that one bout of resistance exercise elicits significant changes in 26 of 33 measured plasma metabolites, reflecting alterations in several biological processes. Furthermore, 12 metabolites demonstrated significant interactions between exercise and age, including organic acids, amino acids, ketones, and keto-acids, which exhibited distinct responses to exercise in young and older adults. Pre-exercise histidine and sarcosine were negatively associated with muscle protein synthesis, as was the pre\/post-exercise fold change in plasma histidine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that while many exercise-responsive metabolites change similarly in young and older adults, several demonstrate age-dependent changes even in the absence of evidence of sarcopenia or frailty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec005\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:bold>Clinical trial registry:<\/jats:bold>\n                      ClinicalTrials.gov\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03350906\" xlink:type=\"simple\">NCT03350906<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0301037","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T13:51:35Z","timestamp":1711633895000},"page":"e0301037","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Metabolomic response to acute resistance exercise in healthy older adults by 1H-NMR"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-9510","authenticated-orcid":true,"given":"Darya","family":"Moosavi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7806-7238","authenticated-orcid":true,"given":"Ivan","family":"Vuckovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawley E.","family":"Kunz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9858-3384","authenticated-orcid":true,"given":"Ian R.","family":"Lanza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,3,28]]},"reference":[{"issue":"1","key":"pone.0301037.ref001","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: revised European consensus on definition and diagnosis.","volume":"48","author":"AJ Cruz-Jentoft","year":"2019","journal-title":"Age Ageing."},{"issue":"6","key":"pone.0301037.ref002","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/db06-1566","article-title":"Aerobic exercise overcomes the age-related insulin resistance of muscle protein metabolism by improving endothelial function and Akt\/mammalian target of rapamycin signaling","volume":"56","author":"S Fujita","year":"2007","journal-title":"Diabetes"},{"issue":"8","key":"pone.0301037.ref003","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1210\/jc.2003-031986","article-title":"Intramuscular and liver triglycerides are increased in the elderly","volume":"89","author":"MG Cree","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"issue":"11","key":"pone.0301037.ref004","doi-asserted-by":"crossref","first-page":"2837","DOI":"10.1016\/j.celrep.2018.02.069","article-title":"Age-Associated Impairments in Mitochondrial ADP Sensitivity Contribute to Redox Stress in Senescent Human Skeletal Muscle","volume":"22","author":"GP Holloway","year":"2018","journal-title":"Cell Rep"},{"issue":"15","key":"pone.0301037.ref005","doi-asserted-by":"crossref","first-page":"5618","DOI":"10.1073\/pnas.0501559102","article-title":"Decline in skeletal muscle mitochondrial function with aging in humans","volume":"102","author":"KR Short","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0301037.ref006","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mad.2017.08.009","article-title":"The physiopathologic role of oxidative stress in skeletal muscle","volume":"170","author":"BM Scicchitano","year":"2018","journal-title":"Mech Ageing Dev"},{"issue":"6","key":"pone.0301037.ref007","first-page":"1194","volume":"153","author":"C L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"The Hallmarks of Aging. 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