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Transcriptional profiling reveals progeroid Ercc1(-/?) mice as a model system for glomerular aging.

ABSTRACT: Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/?) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and aged WT mice in order to establish a novel model for research of aging-related kidney disease.In a principal component analysis, age and genotype emerged as first and second principal components. Hierarchical clustering of all 521 genes differentially regulated between young and old WT and young and old Ercc1(-/?) mice showed cluster formation between young WT and Ercc1(-/?) as well as old WT and Ercc1(-/?) samples. An unexpectedly high number of 77 genes were differentially regulated in both WT and Ercc1(-/?) mice (p?

SUBMITTER: Schermer B

PROVIDER: S-EPMC3751413 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

Schermer Bernhard B Bartels Valerie V Frommolt Peter P Habermann Bianca B Braun Fabian F Schultze Joachim L JL Roodbergen Marianne M Hoeijmakers Jan Hj JH Schumacher Björn B Nürnberg Peter P Dollé Martijn Et ME Benzing Thomas T Müller Roman-Ulrich RU Kurschat Christine E CE

BMC genomics 20130816

<h4>Background</h4>Aging-related kidney diseases are a major health concern. Currently, models to study renal aging are lacking. Due to a reduced life-span progeroid models hold the promise to facilitate aging studies and allow examination of tissue-specific changes. Defects in genome maintenance in the Ercc1(-/Δ) progeroid mouse model result in premature aging and typical age-related pathologies. Here, we compared the glomerular transcriptome of young and aged Ercc1-deficient mice to young and ...[more]

PMID: 23947592

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Project description:BackgroundAging is a major risk factor for the development of many diseases, and the liver, as the most important metabolic organ, is significantly affected by aging. It has been shown that the liver weight tends to increase in rodents and decrease in humans with age. Pigs have a genomic structure, with physiological as well as biochemical features that are similar to those of humans, and have therefore been used as a valuable model for studying human diseases. The molecular mechanisms of the liver aging of large mammals on a comprehensive transcriptional level remain poorly understood. The pig is an ideal model animal to clearly and fully understand the molecular mechanism underlying human liver aging.MethodsIn this study, four healthy female Yana pigs (an indigenous Chinese breed) were investigated: two young sows (180-days-old) and two old sows (8-years-old). High throughput RNA sequencing was performed to evaluate the expression profiles of messenger RNA, long non-coding RNAs, micro RNAs, and circular RNAs during the porcine liver aging process. Gene Ontology (GO) analysis was performed to investigate the biological functions of age-related genes.ResultsA number of age-related genes were identified in the porcine liver. GO annotation showed that up-regulated genes were mainly related to immune response, while the down-regulated genes were mainly related to metabolism. Moreover, several lncRNAs and their target genes were also found to be differentially expressed during liver aging. In addition, the multi-group cooperative control relationships and constructed circRNA-miRNA co-expression networks were assessed during liver aging.ConclusionsNumerous age-related genes were identified and circRNA-miRNA co-expression networks that are active during porcine liver aging were constructed. These findings contribute to the understanding of the transcriptional foundations of liver aging and also provide further references that clarify human liver aging at the molecular level.

Dataset Information

Transcriptional profiling reveals progeroid Ercc1(-/?) mice as a model system for glomerular aging.

Publications

Transcriptional profiling reveals progeroid Ercc1(-/Δ) mice as a model system for glomerular aging.

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