Pharmaceutical interventions in a murine cardiac aging model

Abstract

University of Washington Abstract Pharmaceutical interventions in a murine cardiac aging model Autumn L. Tocchi Chair of Supervisory Committee: Peter S. Rabinovitch MD, PhD Professor of Pathology Heart disease is the number one killer in developed and undeveloped nations, with aging being the number one factor contributing to its diagnosis. Currently, there are no preventative medications to prevent this pathology, especially the increasingly common disorder of heart failure with preserved ejection fraction (HF/pEF). Two therapeutics that might be good preventative medications are rapamycin, an inhibitor of the target of rapamycin pathway that has been shown to extend lifespan, and the tetra-peptide SS-31. Using a model of murine cardiac aging, two experiments were designed to investigate if rapamycin and SS-31 could improve heart function. Using echocardiography, qPCR, and western blots we found that in both conditions, there appears to be no improvement in functional changes. Electron microscopy did show beneficial changes in mitochondrial and cytoskeletal ultrastructure. Additionally, while there are many proteomic changes by mass spectroscopy, these changes were difficult to identify in qPCR or western blot analysis. However, in the SS-31 persistence experiment, a large morphological improvement in the hearts, suggested a positive and persistent benefit of the peptide. While taking the first step in the right direction, future work will need to expand on mouse numbers and parameters measured by qPCR and western blot to better understand what is occurring with these therapies and whether they would be good for humans as a preventative measure for heart disease.