Topic: Myocardial Remodeling and Heart Failure: Aging-related Mechanisms and Intervention Strategies

Heart failure (HF), a leading cause of global morbidity and mortality, is intricately linked to aging, which exacerbates maladaptive myocardial remodeling—a process encompassing cardiomyocyte hypertrophy, fibrosis, inflammation, and metabolic dysregulation. Aging-driven mechanisms such as cellular senescence, mitochondrial dysfunction, oxidative stress, and epigenetic alterations synergistically impair cardiac resilience. Senescent cells accumulate in the aging heart, releasing pro-inflammatory mediators that drive fibrotic remodeling, while mitochondrial decay disrupts bioenergetics, amplifies ROS, and impairs calcium handling, precipitating arrhythmias and contractile dysfunction. Telomere attrition and epigenetic drift further destabilize genomic integrity, and chronic low-grade inflammation (“inflammaging”), coupled with dysregulated neurohormonal signaling, accelerates pathological remodeling. Despite current therapies targeting neurohormonal pathways, aging-associated cardiac decline remains incompletely addressed, necessitating novel strategies. Emerging interventions focus on senolysis to eliminate senescent cells, mitochondrial-targeted antioxidants and NAD+ boosters to restore redox and metabolic balance, and anti-inflammatory agents to counteract inflammaging. Lifestyle modifications such as exercise and caloric restriction have been shown to enhance autophagy and mitochondrial biogenesis, while advances in gene editing and regenerative approaches (e.g., exosome therapy, cardiac reprogramming) aim to rejuvenate the aged myocardium. Personalized medicine, guided by biomarkers of biological aging (e.g., epigenetic clocks), offers the potential to optimize therapeutic timing and efficacy. This Special Issue seeks to highlight cutting-edge research on the interplay between aging and myocardial remodeling, emphasizing mechanistic insights and translational innovations. By bridging molecular discoveries with clinical applications, this collection aims to advance strategies that preserve cardiac function in aging populations, ultimately reducing the burden of HF. We welcome original studies and reviews elucidating novel aging-related pathways, biomarkers, and targeted interventions to reshape the management of age-related heart failure.

Myocardial remodeling, heart failure