Project Summary/Abstract Cardiorenal syndrome is an age-associated pathology where the dysfunction of the heart or kidney induces excess extracellular matrix in the other organ. We propose, and our data supports, that age-associated dysregulation between interorgan signaling promotes cardiorenal syndrome. Comorbidity, heterogeneity and gender differences may be better managed by understanding how age affects kidney-adrenal-heart communication and by what mechanisms these tissues induce fibrosis. This project will transplant adrenal and kidney tissue between young and aged mice to determine how altered interorgan communication drives aging- associated cardiac dysfunction. We will study the interaction of age-associated water-loss and interorgan communication to determine how this impacts cardiorenal aging. Because we find that mammalian renal steroid hormones can induce heart fibrosis in Drosophila by acting through a novel membrane receptor, we will determine how this receptor signals to induce fibrosis and identify the corresponding receptor in mammalian tissues. Overall, this proposal aims to understand how aging impacts interorgan communication to produce age- associated cardiorenal syndrome and fibrosis, using models of Drosophila and mice.