{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T03:45:04Z","timestamp":1791776704177,"version":"4.3.4"},"reference-count":71,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,3,11]],"date-time":"2023-03-11T00:00:00Z","timestamp":1678492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Exercise\u2010induced perturbation of skeletal muscle metabolites is a probable mediator of long\u2010term health benefits in older adults. Although specific metabolites have been identified to be impacted by age, physical activity and exercise, the depth of coverage of the muscle metabolome is still limited. Here, we investigated resting and exercise\u2010induced metabolite distribution in muscle from well\u2010phenotyped older adults who were active or sedentary, and a group of active young adults. Percutaneous biopsies of the vastus lateralis were obtained before, immediately after and 3\u00a0h following a bout of endurance cycling. Metabolite profile in muscle biopsies was determined by tandem mass spectrometry. Mitochondrial energetics in permeabilized fibre bundles was assessed by high resolution respirometry and fibre type proportion was assessed by immunohistology. We found that metabolites of the kynurenine\/tryptophan pathway were impacted by age and activity. Specifically, kynurenine was elevated in muscle from older adults, whereas downstream metabolites of kynurenine (kynurenic acid and NAD<jats:sup>+<\/jats:sup>) were elevated in muscle from active adults and associated with cardiorespiratory fitness and muscle oxidative capacity. Acylcarnitines, a potential marker of impaired metabolic health, were elevated in muscle from physically active participants. Surprisingly, despite baseline group difference, acute exercise\u2010induced alterations in whole\u2010body substrate utilization, as well as muscle acylcarnitines and ketone bodies, were remarkably similar between groups. Our data identified novel muscle metabolite signatures that associate with the healthy ageing phenotype provoked by physical activity and reveal that the metabolic responsiveness of muscle to acute endurance exercise is retained with age regardless of activity levels.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15468-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Kynurenine\/tryptophan pathway metabolites were impacted by age and physical activity in human muscle, with kynurenine elevated in older muscle, whereas downstream products kynurenic acid and NAD<jats:sup>+<\/jats:sup> were elevated in exercise\u2010trained muscle regardless of age.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Acylcarnitines, a marker of impaired metabolic health when heightened in circulation, were elevated in exercise\u2010trained muscle of young and older adults, suggesting that muscle act as a metabolic sink to reduce the circulating acylcarnitines observed with unhealthy ageing.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Despite the phenotypic differences, the exercise\u2010induced response of various muscle metabolite pools, including acylcarnitine and ketone bodies, was similar amongst the groups, suggesting that older adults can achieve the metabolic benefits of exercise seen in young counterparts.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp284142","type":"journal-article","created":{"date-parts":[[2023,2,23]],"date-time":"2023-02-23T05:24:00Z","timestamp":1677129840000},"page":"2165-2188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Exercise and ageing impact the kynurenine\/tryptophan pathway and acylcarnitine metabolite pools in skeletal muscle of older adults"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1341-0725","authenticated-orcid":false,"given":"J. 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