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Research Paper|Volume 8, Issue 3|pp 441—454

Altered lipid metabolism in the aging kidney identified by three layered omic analysis

Fabian Braun1,2, Markus M. Rinschen1,2, Valerie Bartels1,3, Peter Frommolt2,4, Bianca Habermann4,5, Jan H.J. Hoeijmakers6, Björn Schumacher2,7, Martijn E.T. Dollé8, Roman-Ulrich Müller1,2,4, Thomas Benzing1,2,4, Bernhard Schermer1,2,4, Christine E. Kurschat1,2
  • 1Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
  • 2Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany
  • 3Department of Cardiology and Angiology, University of Münster, Münster, Germany
  • 4Systems Biology of Ageing Cologne, University of Cologne, Cologne, Germany
  • 5Max Planck Institute of Biochemistry, Martinsried, Germany
  • 6Department of Cell Biology and Genetics, Medical Genetics Centre, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands
  • 7Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Cologne, Germany
  • 8National Institute of Public Health and the Environment, Centre for Health Protection, Bilthoven, The Netherlands
Received: November 23, 2015Accepted: January 20, 2016Published: February 16, 2016

Copyright: © 2016 Braun et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Aging-associated diseases and their comorbidities affect the life of a constantly growing proportion of the population in developed countries. At the center of these comorbidities are changes of kidney structure and function as age-related chronic kidney disease predisposes to the development of cardiovascular diseases such as stroke, myocardial infarction or heart failure. To detect molecular mechanisms involved in kidney aging, we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by transcriptomic, proteomic and targeted lipidomic methodologies. Interestingly, transcriptome and proteome analyses revealed differential expression of genes primarily involved in lipid metabolism and immune response. Additional lipidomic analyses uncovered significant age-related differences in the total amount of phosphatidylethanolamines, phosphatidylcholines and sphingomyelins as well as in subspecies of phosphatidylserines and ceramides with age. By integration of these datasets we identified Aldh1a1, a key enzyme in vitamin A metabolism specifically expressed in the medullary ascending limb, as one of the most prominent upregulated proteins in old kidneys. Moreover, ceramidase Asah1 was highly expressed in aged kidneys, consistent with a decrease in ceramide C16. In summary, our data suggest that changes in lipid metabolism are involved in the process of kidney aging and in the development of chronic kidney disease.