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Defining Biomarkers of Frailty in the Kidney: Implications for Endobiotic and Xenobiotic Metabolism in Mice

dc.contributor.authorHodgins, Maddison
dc.contributor.copyright-releaseNoen_US
dc.contributor.degreeMaster of Scienceen_US
dc.contributor.departmentDepartment of Pharmacologyen_US
dc.contributor.ethics-approvalNot Applicableen_US
dc.contributor.external-examinern/aen_US
dc.contributor.graduate-coordinatorDenis Dupreen_US
dc.contributor.manuscriptsNoen_US
dc.contributor.thesis-readerMelanie Kellyen_US
dc.contributor.thesis-readerMorgan Langilleen_US
dc.contributor.thesis-supervisorTobias Karakachen_US
dc.date.accessioned2023-08-08T18:09:02Z
dc.date.available2023-08-08T18:09:02Z
dc.date.defence2023-07-17
dc.date.issued2023-08-08
dc.description.abstractFrailty describes individuals with increased susceptibility to adverse health outcomes. The frailty index (FI) quantifies frailty by measuring deficit accumulation. This project aimed to characterize the molecular signature of frailty in the mouse kidney to (a) identify biomarkers for frailty and (b) investigate the impacts of frailty on kidney metabolism. Age-matched female mice with high and low FI scores were selected for RNA sequencing (RNA-Seq). Seven metabolic genes were differentially expressed upon comparing high FI to low FI mice, these included: Ugt1a9/10, Cyp4a12a/b, Akr1c18, Pla2g12b, and Hdc. Quantitative polymerase chain reaction (qPCR) was used to measure expression of these genes in mice with a gradient of FI scores. Finally, metabolic gene expression was examined in mice treated with the angiotensin-converting-enzyme (ACE) inhibitor, enalapril, which has been shown to attenuate FI scores. These data suggest that renal xenobiotic and endobiotic metabolism may be altered by frailty, but further work is necessary.en_US
dc.identifier.urihttp://hdl.handle.net/10222/82764
dc.language.isoenen_US
dc.subjectFrailtyen_US
dc.subjectBiomarkersen_US
dc.subjectMetabolismen_US
dc.subjectKidneyen_US
dc.titleDefining Biomarkers of Frailty in the Kidney: Implications for Endobiotic and Xenobiotic Metabolism in Miceen_US

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