Join Dr. Sandrina Nóbrega-Pereira as she discusses the role of age, epigenetics, and mitochondrial metabolism in the Direct Cardiac Conversion (DCC) of fibroblasts into induced cardiomyocytes (iCMs).

Heart disease remains the leading cause of death in developed nations, underscoring the need for innovative regenerative therapies. One such strategy, Direct Cardiac Conversion (DCC) of fibroblasts into induced cardiomyocytes (iCMs) by forced expression of the transcription factors Mef2c, Gata4, and Tbx5 (MGT), shows promise but is limited in efficacy, especially with age. In this webinar, Dr. Nóbrega-Pereira will discuss recent results from her laboratory exploring the metabolic and age-related constraints affecting DCC in mouse fibroblasts in vitro.

DCC efficiency declines with age, correlating with epigenetic remodeling and altered mitochondrial metabolism, including reduced anabolism, mitochondrial network changes, and a shift toward oxidative phosphorylation. Dr. Nóbrega-Pereira will discuss the consequences of accumulated mitochondrial oxidative stress in older cells on reprogramming efficiency, and how modulation of metabolism in vitro and using dietary interventions in vivo can restore mitochondrial function, reduce oxidative stress, and improve reprogramming outcomes

These interventions were also associated with beneficial changes in histone modification patterns, suggesting a strong link between metabolism, epigenetics, and cell fate conversion. The observed metaboloepigenetic regulation limits to DCC efficiency suggest metabolic interventions may be an effective strategy to enhance cardiac reprogramming in aged cells.