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

Tanmai Nimmagadda

Tanmai Nimmagadda photo

Pronouns: he/him

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: Tanmai Nimmagadda, Skylar Grossberg, 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. Using iPSC-CMs(induced pluripotent stem cell-derived cardiomyocytes) carrying a mutation in the LMNA gene, we can study the effects of aging on cardiac function. Improper expression of proteins responsible for calcium handling in cardiomyocytes underlies the poor contractile function observed in cardiac cells experiencing advanced aging. Through western blot analysis, proteins responsible for Ca2+ activity can be quantified in healthy cardiomyocytes and with the applied ischemic medium. The proteins of interest include the Sarcoplasmic Reticulum Ca+ ATPase (SERCA 2a) protein pump and its inhibiting protein, phospholamban. Ischemic conditions promote over expression of the phospholamban protein, ultimately causing underexpression of the SERCA 2a protein. Evidence supporting the improper regulation of these proteins in cells undergoing cellular senescence provides molecular targets for cardiovascular disease therapies.

Life Science

lsa logoum logo