{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T20:44:13Z","timestamp":1770324253276,"version":"3.49.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Recent pre\u2010clinical evidence suggests that the tryptophan metabolite 3\u2010hydroxyanthranilic acid (3\u2010HAA) and the related enzyme activity along the kynurenine metabolic pathway (KP) are associated with lifespan extension. We aimed to translate these findings into humans and expose exercise training as a potential non\u2010pharmacological intervention to modulate this metabolic hub.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To explore whether recent pre\u2010clinical findings might also be of relevance for humans, we analyzed the evolutionary conservation of KYNU and HAAO, the two core KP enzymes associated with 3\u2010HAA. In a cross\u2010sectional analysis of young\u2010to\u2010middle\u2010aged adults (<jats:italic>N<\/jats:italic>\u2009=\u200984), we examined potential associations of serum 3\u2010HAA and its precursor anthranilic acid with age. We then investigated whether 26\u2009weeks of endurance exercise (increasing intensity (INC) during the intervention period (<jats:italic>n<\/jats:italic>\u2009=\u200917) vs. conventional moderate continuous training (CON) matched for energy expenditure (<jats:italic>n<\/jats:italic>\u2009=\u200917)) impacted 3\u2010HAA levels, related metabolic ratios, and other KP metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that the core KP enzymes associated with 3\u2010HAA are evolutionarily conserved in humans. Serum 3\u2010HAA and its precursor anthranilic acid were consistently associated with age in young\u2010to\u2010middle\u2010aged adults. Both exercise modes tested induced an increase in 3\u2010HAA levels of 134% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and 85% (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) compared with baseline, respectively, without a significant time*group interaction effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We translate the association between systemic 3\u2010HAA levels and age from animal models into humans and highlight longer\u2010term exercise training as an efficient strategy to boost systemic 3\u2010HAA levels in middle\u2010aged adults. Our findings open promising research avenues concerning the mediating role of 3\u2010HAA in training adaptations, health, and longevity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.70041","type":"journal-article","created":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T02:04:22Z","timestamp":1743818662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exercise training restores longevity\u2010associated tryptophan metabolite 3\u2010hydroxyanthranilic acid levels in middle\u2010aged adults"],"prefix":"10.1111","volume":"241","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-8746","authenticated-orcid":false,"given":"Niklas","family":"Joisten","sequence":"first","affiliation":[{"name":"Division of Exercise and Movement Science, Institute for Sport Science University of G\u00f6ttingen  G\u00f6ttingen Germany"},{"name":"Division of Performance and Health (Sports Medicine), Institute for Sport and Sport 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