Cardiac aging: Molecular mechanisms and therapeutic interventions

Cardiac aging is a fundamental driver of cardiovascular diseases (CVDs), the leading cause of global mortality. While age is a non-modifiable risk factor, understanding its underlying molecular basis offers new avenues for therapeutic intervention. This review synthesizes the key mechanisms driving cardiac aging and evaluates promising strategies to counteract them. Our aim is to provide a forward-looking perspective, arguing that a paradigm shift from single-target interventions to synergistic, systems-level approaches is necessary to promote healthy aging and longevity. We delineate the hallmark structural and functional changes of the aging heart, including left ventricular hypertrophy, diastolic dysfunction, and increased fibrosis. We then explore the core molecular pathways, highlighting the critical roles of dysfunctional autophagy, mitochondrial oxidative stress, telomere shortening, and profound epigenetic shifts, particularly the dysregulation of non-coding RNAs such as miR-34a. Building on this mechanistic framework, we assess a range of interventions, from lifestyle modifications like caloric restriction to targeted pharmaceuticals including rapamycin and senolytics. Furthermore, we discuss the potential of next-generation therapies such as microbiome modulation, cell-based regeneration, and gene editing. We conclude that targeting these interconnected aging pathways represents a new frontier in cardiology, with the potential to move beyond disease management and toward extending cardiovascular healthspan.