Iron Overload Accelerates Aging-Associated Kidney Injury in Mice: Implications for Iron Supplementation in the Elderly

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.