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Aging and Disease    2014, Vol. 5 Issue (6) : 356-365     DOI: 10.14366/AD.2014.0500356
Original Article |
Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression
Costa Elísio1, 2, *(), Fernandes João2, 3, Ribeiro Sandra1, 2, Sereno José3, Garrido Patrícia3, Rocha-Pereira Petronila2, 4, Coimbra Susana2, 5, Catarino Cristina1, 2, Belo Luís1, 2, Bronze-da-Rocha Elsa1, 2, Vala Helena6, 7, Alves Rui8, 9, Reis Flávio3, Santos-Silva Alice1, 2
1Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal
2Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
3 Laboratório de Farmacologia e Terapêutica Experimental, Instituto de Imagem Biomédica e Ciências da Vida, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal
4Centro Investigação Ciências da Saúde, Universidade Beira Interior, Covilhã, Portugal
5CESPU, Institute for Research and Advanced Training in Health Sciences and Technologies, Gandhinagar-PRD, Portugal
6Escola Superior Agrária de Viseu, Instituto Politécnico de Viseu, Viseu, Portugal
7Centro de Estudos em Educação, Tecnologias e Saúde, Instituto Politécnico de Viseu, Viseu, Portugal
8Departamento de Nefrologia, CHUC, Coimbra, Portugal
9Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal
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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.

Keywords Anemia      older population      elderly      renal failure      inflammation      erythropoietic disturbances     
Corresponding Authors: Costa Elísio     E-mail:
Issue Date: 21 November 2014
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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
Cite this article:   
Costa Elísio,Fernandes João,Ribeiro Sandra, et al. Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression[J]. Aging and Disease, 2014, 5(6): 356-365.
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Table 1.  Body and tissue weight, trophism indexes, hematological, biochemical and inflammatory data, iron metabolism and EPO levels in young and old rats
Table 2.  Scoring and distribution of glomerular and tubular lesions in the groups under study at the final time
Figure 1.  Transferrin receptor 2 (TfR2), hepcidin (Hamp), ferroportin (SLC40A1), hemojuvelin (HJV), transferrin (TF), hemochromatosis (Hfe) gene expression in liver tissue for both groups of rats (young and old).
Figure 2.  Divalent metal transporter 1 (DMT1) gene expression in duodenal tissues.
Figure 3.  Erythropoietin (EPO) and erythropoietin receptor (EPOR) gene expression in liver (A and C) and kidney (B and D).
Figure 4.  Renal histological changes associated with aging. (A) Example of atherosclerotic grade 1 lesions found in arteries of old rats (X40), intimal thickening (I) less than thickness of media (M). (B) Dilatation of the Bowman´s Space (X20), N–normal glomerulus, BS – Bowman´s Space. (C) Arteries of young rats without changes (X40). (D) Normal glomerulus.
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