This study aimed to identify novel plasma metabolic signatures with possible clinical relevance during the aging process. A biochemical quantitative phenotyping platform, based on targeted electrospray ionization tandem mass spectrometry technology, was used for the identification of any eventual perturbed biochemical pathway by the aging process in prospectively collected peripheral blood plasma from 166 individuals representing the population of São Paulo city, Brazil. Indoleamine 2,3-dioxygenase (IDO) activity (Kyn/Trp) was significantly elevated with age, and among metabolites most associated with elevations in IDO, one of the strongest correlations was with arginase (Orn/Arg), which could also facilitate the senescence process of the immune system. Hyperactivity of IDO was also found to correlate with increased blood concentrations of medium-chain acylcarnitines, suggesting that deficiencies in beta-oxidation may also be involved in the immunosenescence process. Finally, our study provided evidence that the systemic methylation status was significantly increased and positively correlated to IDO activity. In the present article, besides identifying elevated IDO activity exhibiting striking parallel association with the aging process, we additionally identified increased arginase activity as an underlying biochemical disturbance closely following elevations in IDO. Our findings support interventions to reduce IDO or arginase activities in an attempt to preserve the functionality of the immune system, including modulation of myeloid-derived suppressor cells (MDSCs), T cells, macrophages, and dendritic cells’ function, in old individuals/patients.

中文翻译：

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人类衰老过程中吲哚胺 2,3-双加氧酶 (IDO) 和精氨酸酶之间的关键分子串扰可能成为免疫衰老控制的目标吗？

本研究旨在确定衰老过程中可能具有临床相关性的新血浆代谢特征。基于靶向电喷雾电离串联质谱技术的生化定量表型平台，用于从代表巴西圣保罗市人口的 166 名个体前瞻性收集的外周血浆中鉴定衰老过程中任何最终受到干扰的生化途径。吲哚胺 2,3-双加氧酶 (IDO) 活性 (Kyn/Trp) 随着年龄的增长而显着升高，在与 IDO 升高最相关的代谢物中，最强的相关性之一是与精氨酸酶 (Orn/Arg)，这也可能促进免疫系统的衰老过程。还发现 IDO 的过度活跃与中链酰基肉碱的血液浓度增加相关，这表明 β-氧化的缺陷也可能与免疫衰老过程有关。最后，我们的研究提供了证据表明全身甲基化状态显着增加并且与 IDO 活性呈正相关。在本文中，除了确定 IDO 活性升高与衰老过程具有惊人的平行关联外，我们还确定精氨酸酶活性升高是紧随 IDO 升高之后的潜在生化紊乱。我们的研究结果支持减少 IDO 或精氨酸酶活性的干预措施，以试图保持免疫系统的功能，包括调节老年个体/患者的骨髓源性抑制细胞 (MDSC)、T 细胞、巨噬细胞和树突状细胞的功能。