Modeling cardiac aging with stem cell-derived cardiomyocytes carrying a mutation for advanced aging – UROP Spring Symposium 2023

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

Skylar Grossberg

Skylar Grossberg photo

Pronouns: she/her

Research Mentor(s): Andre Monteiro Da Rocha
Research Mentor School/College/Department: Cardiology – CVC Cardiovascular Regeneration Core / Medicine
Program: UROPF
Session: Session 7 (4:40pm – 5:30pm)
Authors: Skylar Grossberg , Tanmai Nimmagadda , Andre Monteiro da Rocha

Abstract

Aging is characterized by a myriad of physiological changes, making aging difficult to study and apprehend. Mutations in the LMNA gene have been linked to genomic instability resulting in a progressive, advanced aging disease: Hutchinson-Gilford progeria syndrome. A relatively new technique involving the use of cell lines- human induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)- carrying such mutations, help overcome the limitations concerning age-related research. Using iPSC-CMs carrying a mutation in the LMNA gene, we are able to study cardiac contractile function under different conditions. Cardiovascular function is highly dependent upon appropriate calcium regulation, inappropriate expression of Sarcoplasmic Reticulum Ca(2+)-ATPase pump (SERCA 2a) and its inhibiting protein – phospholamban(PLN) – are critical in maintaining balanced intracellular calcium concentration. Changes in calcium levels have been previously seen in diseased, aged, cardiomyocytes. Western blot analysis can be performed to determine SERCA 2a levels as well as phospholamban under an ischemic medium and ideal conditions. By understanding the differences in expression of SERCA 2a and PLN, possible targeted gene-based therapies will have greater potential to transpire to preserve cardiac function in mature individuals.

Life Science

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