Modeling cardiac aging with stem cell-derived cardiomyocytes carrying a mutation for advanced aging – UROP Spring Symposium 2025

Modeling cardiac aging with stem cell-derived cardiomyocytes carrying a mutation for advanced aging

Alex Buzdugan

Research Mentor(s): Andre Monteiro Da Rocha
Mentor Department: Cardiology – CVC Cardiovascular Regeneration Core
Authors: Alex Buzdugan, Andre Monteiro da Rocha
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 59

Abstract

Diastolic dysfunction, a condition where the heart muscle does not relax properly during diastole, is a major feature of cardiac aging. In the heart, calsequestrin-2 is the predominant calsequestrin isoform, but calsequestrin-1 is also expressed and could take a compensatory role when CASQ2 is downregulated or repressed. The main function of calsequestrins is to store calcium and to buffer calcium levels in muscle cells, a role that is crucial in allowing the heart muscle to properly contract and relax. Our hypothesis is that aging alters the expression of calsequestrin-1 and -2 in the heart. To test this hypothesis, we will utilize hearts from young (<4 months old) or aged (>20 months old), male and female mice . These mice were dissected, the hearts were embedded in paraffin and histology sections obtained for immunofluorescence preparation. Immunofluorescence is being performed and microscopy images acquired to determine the expression patterns/levels of calsequestrins for analysis with FIJI-ImageJ. We expect to observe an age-related decrease in expression of calsequestrin-1 and -2, consistent with preliminary mRNA sequencing data obtained for cardiomyocytes carrying a mutation causative of advanced aging. Understanding the mechanisms behind diastolic dysfunction, a precursor to heart failure, is crucial given the high prevalence of diastolic dysfunction in the aging population

lsa logoum logo