Chultemsuren Mungunchimeg, Song Soo-Jin, Han Ki-Hwan, Shin Jung-A
Department of Anatomy, Ewha Womans University College of Medicine, Seoul 07804, Republic of Korea.
Nutrients. 2025 Aug 8;17(16):2580. doi: 10.3390/nu17162580.
Although essential for oxygen transport and DNA synthesis, excess iron is toxic and can damage organs such as the kidneys. Research has shown that iron overload induces kidney injury, and aging contributes to kidney dysfunction through functional and structural changes. The interaction between iron overload and aging remains poorly understood. Therefore, this study investigated their combined effects on renal microstructure and function using an iron-dextran-injected mouse model. Young and old mice were divided into control and iron overload groups, renal function was evaluated by serum creatinine and albuminuria, and urinary iron excretion was also measured to assess iron handling. The structural changes were assessed using histological analysis and electron microscopy. Although the iron overload groups had similar blood iron levels, the old iron overload group exhibited significantly higher levels of albuminuria, urinary iron excretion, and serum creatinine compared with the young group. In the iron overload model, histological and ultrastructural analyses demonstrated iron accumulation in mesangial and endothelial cells, glomerular basement membrane thickening, and foot process widening, which were more pronounced in aged mice, suggesting that aging exacerbates iron-induced kidney injury. These findings demonstrate that aging increases susceptibility to iron-induced kidney injury, as shown by the accelerated glomerular injury observed in iron-overloaded aged mice. Therefore, elucidating the effects of aging on iron metabolism may contribute to identifying approaches for reducing age-associated renal injury.
尽管铁对于氧气运输和DNA合成至关重要，但过量的铁具有毒性，会损害诸如肾脏等器官。研究表明，铁过载会引发肾损伤，而衰老则通过功能和结构变化导致肾功能障碍。铁过载与衰老之间的相互作用仍知之甚少。因此，本研究使用右旋糖酐铁注射小鼠模型，研究了它们对肾脏微观结构和功能的联合影响。将年轻和年老小鼠分为对照组和铁过载组，通过血清肌酐和蛋白尿评估肾功能，并测量尿铁排泄以评估铁的处理情况。使用组织学分析和电子显微镜评估结构变化。尽管铁过载组的血铁水平相似，但与年轻组相比，老年铁过载组的蛋白尿、尿铁排泄和血清肌酐水平显著更高。在铁过载模型中，组织学和超微结构分析显示系膜细胞和内皮细胞中铁的积累、肾小球基底膜增厚以及足突增宽，这些在老年小鼠中更为明显，表明衰老会加剧铁诱导的肾损伤。这些发现表明，衰老会增加对铁诱导肾损伤的易感性，铁过载老年小鼠中观察到的肾小球损伤加速就证明了这一点。因此，阐明衰老对铁代谢的影响可能有助于确定减少与年龄相关肾损伤的方法。
