Short-term rapamycin persistently improves cardiac function after cessation of treatment in aged male and female mice.

by Ellen K Quarles

Institution: University of Washington
Year: 2018
Keywords: aging; cardiac; echocardiography; persistence; proteomics; rapamycin; Aging; Pathology; Molecular biology; Pathology
Posted: 02/01/2018
Record ID: 2219052
Full text PDF: http://hdl.handle.net/1773/40953


Cardiac aging is an intrinsic process that results in impaired cardiac function and dysregulation of cellular and molecular quality control mechanisms. These effects are evident in the decline of diastolic function, increase in left ventricular hypertrophy, metabolic substrate shifts, and alterations to the cardiac proteome. This thesis covers the quality control mechanisms that are associated with cardiac aging, results from an anti-aging intervention in aged mice, and a review of mitochondrial dysfunction in the heart. Chapter one is a review of the quality control mechanisms in aging myocardium. Chapter two consists of the results of several mouse experiments that compare the cardiac function, proteomes, and metabolomes of aged and young controls, along with rapamycin treated aged mice. The novelty of this study comes from the inclusion of a group of animals treated only transiently with the drug, then followed for eight weeks post-drug-removal. This persistence cohort may hold clues to deriving long-lasting benefits of rapamycin with only transient treatment. Chapter three includes more results from the cohorts used in chapter two, from work done by our collaborators in two laboratories at the University of Washington. Finally, chapter four is a review of the mechanisms and phenotypes of mitochondrial dysfunction in the aging heart. The goal of my thesis work is to test the persistence of the improvement of cardiac function by rapamycin treatment, and use the correlating changes in the cardiac proteome and metabolome to discover a novel mechanism of functional improvement of the heart in aged animals.Advisors/Committee Members: Rabinovitch, Peter S (advisor).