Impact of Cellular Senescence on Age-Related Myocardial Dysfunction: A Molecular Imaging Approach
Abstract
The proposed project addresses the Fiscal Year 2018 Peer Reviewed Medical Research Program Topic Area ?Cardiomyopathy.? It is relevant to areas of encouragement ?Improve understanding of the pathophysiology of cardiomyopathies? and ?Improve diagnosis and treatment of primary and secondary cardiomyopathies.? Epidemiologic evidence shows that heart muscle stiffness increases during aging. The number of senescent cell increase during aging in many tissues including in the heart. Those senescent cells are responsible of low level of inflammation and scar-like tissue formation that could explain the stiffening of the heart muscle observed during aging. However, this has not been directly demonstrated. In this study, we propose to generate a genetic mouse model where we can induce heart cell senescence. In those animals, we will follow the stiffening of the heart muscle by echocardiography and compare it to the amount of senescent cell in the heart. If as we hypothesized, the presence of senescent cell is responsible of heart stiffening with age, this means that new treatments targeting the senescent cells can be used to treat this condition. There is no existing methods to visualize the presence (and amount) of senescent cell in a living organism. A recent study has identified a specific marker of senescent cells (MDA-vimentin) with good characteristics to be target. In a second part of our study, we propose to develop and validate a medical imaging method to visualize senescent cells in a living organism by targeting this marker. This method would be useful for further studies in animals (such as the evaluation of new treatments) and for humans, in a first time to validate that the finding in animals are relevant for the human disease and later for other applications (such as finding the people who would beneficiate for a given treatment or assess if the treatment is working without waiting years to find out using other measurements).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 05, 2019
- Source ID
- W81XWH1910107
Entities
People
- Jakub Toczek
Organizations
- United States Army
- Yale University