Joisten Niklas, Reuter Marcel, Rosenberger Friederike, Venhorst Andreas, Kupjetz Marie, Walzik David, Schenk Alexander, McCann Adrian, Ueland Per Magne, Meyer Tim, Zimmer Philipp
Division of Exercise and Movement Science, Institute for Sport Science, University of Göttingen, Göttingen, Germany.
Division of Performance and Health (Sports Medicine), Institute for Sport and Sport Science, TU Dortmund University, Dortmund, Germany.
Acta Physiol (Oxf). 2025 May;241(5):e70041. doi: 10.1111/apha.70041.
Recent pre-clinical evidence suggests that the tryptophan metabolite 3-hydroxyanthranilic acid (3-HAA) 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-pharmacological intervention to modulate this metabolic hub.
To explore whether recent pre-clinical 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-HAA. In a cross-sectional analysis of young-to-middle-aged adults (N = 84), we examined potential associations of serum 3-HAA and its precursor anthranilic acid with age. We then investigated whether 26 weeks of endurance exercise (increasing intensity (INC) during the intervention period (n = 17) vs. conventional moderate continuous training (CON) matched for energy expenditure (n = 17)) impacted 3-HAA levels, related metabolic ratios, and other KP metabolites.
We demonstrate that the core KP enzymes associated with 3-HAA are evolutionarily conserved in humans. Serum 3-HAA and its precursor anthranilic acid were consistently associated with age in young-to-middle-aged adults. Both exercise modes tested induced an increase in 3-HAA levels of 134% (p < 0.001) and 85% (p < 0.001) compared with baseline, respectively, without a significant time*group interaction effect.
We translate the association between systemic 3-HAA levels and age from animal models into humans and highlight longer-term exercise training as an efficient strategy to boost systemic 3-HAA levels in middle-aged adults. Our findings open promising research avenues concerning the mediating role of 3-HAA in training adaptations, health, and longevity.
最近的临床前证据表明，色氨酸代谢产物3-羟基邻氨基苯甲酸（3-HAA）以及犬尿氨酸代谢途径（KP）中的相关酶活性与寿命延长有关。我们旨在将这些发现转化到人类身上，并揭示运动训练作为一种潜在的非药物干预手段来调节这个代谢枢纽。
为了探究最近的临床前研究结果是否也适用于人类，我们分析了与3-HAA相关的两种核心KP酶KYNU和HAAO的进化保守性。在一项针对青年至中年成年人（N = 84）的横断面分析中，我们研究了血清3-HAA及其前体邻氨基苯甲酸与年龄之间的潜在关联。然后，我们调查了26周的耐力运动（干预期间强度增加（INC）组，n = 17；与能量消耗匹配的传统中等强度持续训练（CON）组，n = 17）是否会影响3-HAA水平、相关代谢比率以及其他KP代谢产物。
我们证明，与3-HAA相关的核心KP酶在人类中具有进化保守性。在青年至中年成年人中，血清3-HAA及其前体邻氨基苯甲酸始终与年龄相关。与基线相比，两种测试的运动模式分别使3-HAA水平升高了134%（p < 0.001）和85%（p < 0.001），且无显著的时间*组交互作用效应。
我们将动物模型中全身3-HAA水平与年龄之间的关联转化到了人类身上，并强调长期运动训练是提高中年成年人全身3-HAA水平的有效策略。我们的研究结果为3-HAA在训练适应、健康和长寿中的中介作用开辟了有前景的研究途径。
