title: Altered lipid metabolism in the aging kidney identified by three layered omic analysis.
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.
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Braun
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Rinschen
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Department of Cardiology and Angiology, University of Münster, Münster, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Bartels
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Systems Biology of Ageing Cologne, University of Cologne, Cologne, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Frommolt
authors.affiliation: Systems Biology of Ageing Cologne, University of Cologne, Cologne, Germany.|Max Planck Institute of Biochemistry, Martinsried, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Habermann
authors.affiliation: Department of Cell Biology and Genetics, Medical Genetics Centre, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.
authors.forename: Jan H J
authors.initials: JH
authors.lastname: Hoeijmakers
authors.affiliation: Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Institute for Genome Stability in Aging and Disease, Medical Faculty, University of Cologne, Cologne, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Schumacher
authors.affiliation: National Institute of Public Health and the Environment, Centre for Health Protection, Bilthoven, The Netherlands.
authors.forename: Martijn E T
authors.initials: ME
authors.lastname: Dollé
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Systems Biology of Ageing Cologne, University of Cologne, Cologne, Germany.
authors.forename: Roman-Ulrich
authors.initials: RU
authors.lastname: Müller
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Systems Biology of Ageing Cologne, University of Cologne, Cologne, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Benzing
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.|Systems Biology of Ageing Cologne, University of Cologne, Cologne, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schermer
authors.affiliation: Department II of Internal Medicine and Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.|Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Kurschat
mesh_terms: D055573:Acid Ceramidase / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002518:Ceramides / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D050356:Lipid Metabolism; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010743:Phospholipids / Q000378:metabolism; D040901:Proteomics
chemical_list: D002518:Ceramides; D010743:Phospholipids; D055573:Acid Ceramidase; C526734:Asah1 protein, mouse
keywords: gene expression profiling; lipidomics; microarray analysis; proteomics; renal aging