Impact of Cellular Senescence on Age Related Myocardial Dysfunction: A Molecular Imaging Approach
Abstract
Epidemiologic evidence shows alteration of myocardial properties with age resulting in progressive decline in diastolic function. The presence of a population of senescent cardiomyocytes and the soluble factors they secrete (senescence-associated secretory phenotype) could be a major player in the progressive deterioration of myocardial function observed during aging. To test this hypothesis, we propose 1) to generate a new model of cardiac-specific inducible senescence and evaluate cardiac function in association with cellular senescence and 2) to develop a method for in vivo imaging of cellular senescence. The animal model of cardiac-specific inducible senescence was generated by crossing mice with cardiac specific inducible Cre recombinase (MHC-MerCreMer) with enhancer of zeste homolog 2-floxed mice (Ezh2fl/fl), enabling tissue-specific conditional deletion of Ezh2, a key component of a protein complex involved in the repression of p16INK4a, a master regulator of cellular senescence. .
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2020
- Accession Number
- AD1108271
Entities
People
- Jakub Toczek
Organizations
- Yale University