title: Metallothioneins and renal ageing.
abstract: Human lifespan is increasing continuously and about one-third of the population >70 years of age suffers from chronic kidney disease. The pathophysiology of the loss of renal function with ageing is unclear.
  
  
  
  We determined age-associated gene expression changes in zero-hour biopsies of deceased donor kidneys without laboratory signs of impaired renal function, defined as a last serum creatinine >0.96 mg/dL in females and >1.18 mg/dL in males, using microarray technology and the Significance Analysis of Microarrays routine. Expression changes of selected genes were confirmed by quantitative polymerase chain reaction and in situ hybridization and immunohistochemistry for localization of respective mRNA and protein. Functional aspects were examined in vitro.
  
  
  
  Donors were classified into three age groups (<40, 40-59 and >59 years; Groups 1, 2 and 3, respectively). In Group 3 especially, genes encoding for metallothionein (MT) isoforms were more significantly expressed when compared with Group 1; localization studies revealed predominant staining in renal proximal tubular cells. RPTEC/TERT1 cells overexpressing MT2A were less susceptible towards cadmium chloride-induced cytotoxicity and hypoxia-induced apoptosis, both models for increased generation of reactive oxygen species.
  
  
  
  Increased expression of MTs in the kidney with ageing might be a protective mechanism against increased oxidative stress, which is closely related to the ageing process. Our findings indicate that MTs are functionally involved in the pathophysiology of ageing-related processes.
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Leierer
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Rudnicki
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Susie-Jane
authors.initials: SJ
authors.lastname: Braniff
authors.affiliation: Emergentec Biodevelopment GmbH, Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Perco
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Koppelstaetter
authors.affiliation: Emergentec Biodevelopment GmbH, Vienna, Austria.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Mühlberger
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Eder
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Kerschbaum
authors.affiliation: Department of Pharmacology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwarzer
authors.affiliation: Department of Internal Medicine VI, Clinical Immunology and Infectious Diseases, Medical University, Innsbruck, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Schroll
authors.affiliation: Department of Internal Medicine VI, Clinical Immunology and Infectious Diseases, Medical University, Innsbruck, Austria.
authors.forename: Günter
authors.initials: G
authors.lastname: Weiss
authors.affiliation: Center of Operative Medicine, Department of Visceral, Transplant and Thoracic Surgery, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
authors.affiliation: Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Department of General, Visceral and Transplant Surgery, University of Tübingen, Tübingen, Germany.
authors.forename: Alfred
authors.initials: A
authors.lastname: Königsrainer
authors.affiliation: Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University Vienna, Vienna, Austria.
authors.forename: Georg A
authors.initials: GA
authors.lastname: Böhmig
authors.affiliation: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Gert
authors.initials: G
authors.lastname: Mayer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008668:Metallothionein / Q000378:metabolism*; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species; D008668:Metallothionein
keywords: ageing; chronic kidney disease; gene expression; hypoxia; metallothionein