Epigenetic Regulation of Myocyte Proliferation in Cardiovascular Aging: Mechanisms and Therapeutic Potential

Cardiovascular aging is a major contributor to the global burden of heart disease, characterized by structural remodeling, metabolic alterations, and a marked decline in regenerative capacity. One of the most significant challenges in the aging heart is the progressive loss of cardiomyocyte proliferative potential. This limits the heart’s ability to repair itself following injury and contributes to the pathogenesis of age-associated conditions such as heart failure and ischemic heart disease.

Recent advances have highlighted the pivotal role of molecular and cellular mechanisms, particularly epigenetic regulation, in orchestrating the suppression of myocyte proliferation during cardiovascular aging. Modifications such as DNA methylation, histone modification, non-coding RNAs, and chromatin remodeling form a complex regulatory network that silences genes involved in the cardiomyocytes cell cycle. These changes are not only markers of aging but also drivers of the senescent phenotype, creating a cellular environment resistant to regeneration.

Importantly, many of these alterations are reversible, making them attractive therapeutic targets. Emerging strategies, including the use of small molecule modulators, miRNA or noncoding RNA antagonists, and chromatin remodeling agents—are being explored to rejuvenate the aging heart and promote its functional recovery. The integration of disease modeling, single-cell technologies, and gene editing tools is rapidly advancing our understanding of cardiac aging and its translational potential.

This Frontiers Research Topic welcomes original research articles, reviews, and perspectives focused on the control of myocyte proliferation and cardiac regenerative capacity in the context of cardiovascular aging. Submissions may address, but are not limited to:
• Mechanistic studies of cellular and molecular alterations affecting cardiomyocytes proliferation;
• The role of non-coding RNAs in regulating myocytes proliferation in the aging hearts;
• Interventions targeting regulatory networks and signaling pathways for cardiac rejuvenation;
• Cross-talk between cellular senescence, inflammation, and regeneration;
• Disease biology insights into how aging disrupts cardiomyocyte renewal in heart failure and ischemic heart disease;
• Preclinical and clinical strategies for therapeutic reactivation of cardiomyocyte proliferation;
• Technological innovations in studying the cellular and spatial dynamics of cardiac aging.

By bringing together cutting-edge findings and conceptual advances, this collection aims to foster a deeper understanding of the biological barriers to cardiac regeneration and pave the way for innovative therapies to address age-related heart disease.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Conceptual Analysis
• Data Report
• Editorial
• FAIR² Data
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Cardiovascular aging, Epigenetic regulation, Cardiomyocyte proliferation, Regeneration, Therapeutic targets

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.