Key words: cardiac aging; RNA-seq; transcriptome; genome stability; hiPSC-CMs; progeria

"Healthy aging: the heart of the matter is outside of the heart"

The studies for this dissertation attempted to identify the biological processes that lie at the root of the very complex phenomenon of cardiac aging. This experimental work has made use of murine models, which are traditionally the animal models of choice for translational work in the cardiovascular research field. In the study mice were used that were naturally aged in combination with four accelerated aging mouse models, the latter ones carrying mutations affecting specific pathways commonly regarded as contributors to aging. Additionally, the study reached for a new model, cardiomyocytes derived from human induced Pluripotent Stem Cells (hiPSC) clones, which are growing increasingly impactful in the cardiovascular field as one of the first human-based experimental platforms. The hiPSCs differentiated in vitro in cardiac cells have been applied specifically for the study of the Hutchinson-Gilford progeria syndrome, a genetic condition characterized by the dramatic, rapid appearance of aging from early childhood.

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