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

Abstract

Frailty 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.