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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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

ABSTRACT: Aging-related diseases and their comorbidities affect the life quality of a constantly growing proportion of our population. Age-associated changes of kidney structure and function are considerable contributors to the dramatically increased incidence of chronic kidney disease world-wide which has been identified to be a prominent cardiovascular risk factor. In order to detect molecular mechanisms involved in kidney aging we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by a three-layered omics strategy. To this end, transcriptomic, proteomic and targeted lipidomic profiles of young and aged mice were generated and integrated. Transcriptome and proteome analyses revealed differential expression of genes involved primarily 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, while total ceramide levels remained unchanged. 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. 14 weeks females (4 replicates); 96 weeks females (5 replicates)

ORGANISM(S): Mus musculus

SUBMITTER: Christine Kurschat

PROVIDER: E-GEOD-74463 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Project description:Aging-related diseases and their comorbidities affect the life quality of a constantly growing proportion of our population. Age-associated changes of kidney structure and function are considerable contributors to the dramatically increased incidence of chronic kidney disease world-wide which has been identified to be a prominent cardiovascular risk factor. In order to detect molecular mechanisms involved in kidney aging we analyzed gene expression profiles of kidneys from adult and aged wild-type mice by a three-layered omics strategy. To this end, transcriptomic, proteomic and targeted lipidomic profiles of young and aged mice were generated and integrated. Transcriptome and proteome analyses revealed differential expression of genes involved primarily 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, while total ceramide levels remained unchanged. 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.

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