Costa Elísio, Fernandes João, Ribeiro Sandra, Sereno José, Garrido Patrícia, Rocha-Pereira Petronila, Coimbra Susana, Catarino Cristina, Belo Luís, Bronze-da-Rocha Elsa, Vala Helena, Alves Rui, Reis Flávio, Santos-Silva Alice
Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal ; Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; Laboratório de Farmacologia e Terapêutica Experimental, Instituto de Imagem Biomédica e Ciências da Vida, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
Aging Dis. 2013 Dec 23;5(6):356-65. doi: 10.14366/AD.2014.0500356. eCollection 2014 Dec.
Our aim was to contribute to a better understanding of the pathophysiology of anemia in elderly, by studying how aging affects renal function, iron metabolism, erythropoiesis and the inflammatory response, using an experimental animal model. The study was performed in male Wistar, a group of young rats with 2 months age and an old one with 18 months age. Old rats presented a significant higher urea, creatinine, interferon (INF)-gamma, ferritin and soluble transferrin receptor serum levels, as well as increased counts of reticulocytes and RDW. In addition, these rats showed significant lower erythropoietin (EPO) and iron serum levels. Concerning gene expression of iron regulatory proteins, old rats presented significantly higher mRNA levels of hepcidin (Hamp), transferrin (TF), transferrin receptor 2 (TfR2) and hemojuvelin (HJV); divalent metal transporter 1 (DMT1) mRNA levels were significantly higher in duodenal tissue; EPO gene expression was significantly higher in liver and lower in kidney, and the expression of the EPOR was significantly higher in both liver and kidney. Our results showed that aging is associated with impaired renal function, which could be in turn related with the inflammatory process and with a decline in EPO renal production. Moreover, we also propose that aging may be associated with INF-gamma-induced inflammation and with alterations upon iron regulatory proteins gene expression.
我们的目的是通过使用实验动物模型研究衰老如何影响肾功能、铁代谢、红细胞生成和炎症反应，从而有助于更好地理解老年人贫血的病理生理学。该研究在雄性Wistar大鼠中进行，一组为2个月龄的年轻大鼠，另一组为18个月龄的老年大鼠。老年大鼠的尿素、肌酐、干扰素（INF）-γ、铁蛋白和可溶性转铁蛋白受体血清水平显著更高，网织红细胞计数和红细胞分布宽度（RDW）也增加。此外，这些大鼠的促红细胞生成素（EPO）和血清铁水平显著更低。关于铁调节蛋白的基因表达，老年大鼠的铁调素（Hamp）、转铁蛋白（TF）、转铁蛋白受体2（TfR2）和血色素沉着症相关蛋白（HJV）的mRNA水平显著更高；十二指肠组织中二价金属转运体1（DMT1）的mRNA水平显著更高；EPO基因表达在肝脏中显著更高而在肾脏中更低，并且促红细胞生成素受体（EPOR）在肝脏和肾脏中的表达均显著更高。我们的结果表明，衰老与肾功能受损有关，这反过来可能与炎症过程以及肾脏EPO生成的下降有关。此外，我们还提出衰老可能与INF-γ诱导的炎症以及铁调节蛋白基因表达的改变有关。
