Aging Dis. 2013 Dec 23;5(6):356-65. doi: 10.14366/AD.2014.0500356. eCollection 2014 Dec.

Aging is Associated with Impaired Renal Function, INF-gamma Induced Inflammation and with Alterations in Iron Regulatory Proteins Gene Expression.

Costa E¹, Fernandes J², Ribeiro S¹, Sereno J³, Garrido P³, Rocha-Pereira P⁴, Coimbra S⁵, Catarino C¹, Belo L¹, Bronze-da-Rocha E¹, Vala H⁶, Alves R⁷, Reis F³, Santos-Silva A¹.

Author information

1: 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.
2: 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.
3: Laboratório de Farmacologia e Terapêutica Experimental, Instituto de Imagem Biomédica e Ciências da Vida, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
4: Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; Centro Investigação Ciências da Saúde, Universidade Beira Interior, Covilhã, Portugal.
5: Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal ; CESPU, Institute for Research and Advanced Training in Health Sciences and Technologies, Gandhinagar-PRD, Portugal.
6: Escola Superior Agrária de Viseu, Instituto Politécnico de Viseu, Viseu, Portugal ; Centro de Estudos em Educação, Tecnologias e Saúde, Instituto Politécnico de Viseu, Viseu, Portugal.
7: Departamento de Nefrologia, CHUC, Coimbra, Portugal ; Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.

Abstract

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.