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Abstract：
Kidney dysfunction is particularly important in systemic organ injuries caused by aging. Metabolomics are utilized in this study to explore the mechanism of kidney dysfunction during aging by the identification of metabolites and the characterization of metabolic pathways. We analyzed the serum biochemistry and kidney histopathology of male Kunming mice aged 3 months and 24 months and found that the aged mice had inflammatory lesions, aggravated fibrosis, and functional impairment. A high-resolution untargeted metabolomics analysis revealed that the endogenous metabolites in the kidneys and urine of the mice were significantly changed by 25 and 20 metabolites, respectively. A pathway analysis of these differential metabolites revealed six key signaling pathways, namely, D-glutamine and D-glutamate metabolism, purine metabolism, the citrate cycle [tricarboxylic acid (TCA) cycle], histidine metabolism, pyruvate metabolism, and glyoxylate and dicarboxylate metabolism. These pathways are involved in amino acid metabolism, carbohydrate metabolism, and nucleotide metabolism, and these can lead to immune regulation, inflammatory responses, oxidative stress damage, cellular dysfunction, and bioenergy disorders, and they are closely associated with aging and kidney insufficiency. We also screened nine types of sensitive metabolites in the urine as potential biomarkers of kidney dysfunction during the aging process to confirm their therapeutic targets in senior-induced kidney dysfunction and to improve the level of risk assessment for senile kidney injury.
摘要：
肾功能障碍在衰老引起的全身器官损伤中尤为重要。本研究利用代谢组学通过代谢产物的鉴定和代谢途径的表征来探索衰老过程中肾功能障碍的机制。我们分析了3月龄和24月龄雄性昆明种小鼠的血清生化和肾脏组织病理学，发现老年小鼠有炎性病变，纤维化加重，和功能损害。高分辨率非靶向代谢组学分析显示，小鼠肾脏和尿液中的内源性代谢产物被25和20种代谢产物显著改变，分别。对这些差异代谢物的途径分析揭示了六个关键的信号通路，即,D-谷氨酰胺和D-谷氨酸代谢，嘌呤代谢,柠檬酸盐循环[三羧酸(TCA)循环]，组氨酸代谢，丙酮酸代谢，和乙醛酸和二羧酸代谢。这些途径涉及氨基酸代谢，碳水化合物代谢，和核苷酸代谢，这些可以导致免疫调节，炎症反应，氧化应激损伤，细胞功能障碍，和生物能源失调，它们与衰老和肾功能不全密切相关。我们还筛选了尿液中的9种敏感代谢物作为衰老过程中肾功能损害的潜在生物标志物，以确定其在老年肾损害中的治疗目标，并提高老年肾损伤的风险评估水平。
