Novel immunoinformatics-guided activation of CISD1 with compound 4'-methoxy-3',5,7-trihydroxyflavanone for the prevention of age-related cardiomyopathy.

Abstract

Aging is a principal driver of cardiomyopathy, characterized by mitochondrial dysfunction, oxidative stress, and progressive telomere shortening in cardiomyocytes. These pathological changes impair cellular bioenergetics and regenerative capacity, accelerating cardiac deterioration. However, targeted interventions to mitigate these effects remain limited. This research investigates the therapeutic potential of CISD1 activation as a novel strategy to counteract aging-associated cardiac decline. Using advanced Immunoinformatic approaches, including molecular docking, protein structure modelling, and molecular dynamics simulations, we assess the role of CISD1 upregulation in enhancing mitochondrial bioenergetics, reducing oxidative stress, and preserving telomere integrity. Our Immunoinformatic findings reveal that CISD1 activation stabilizes mitochondrial function, mitigates oxidative damage, and slows telomere attrition, thereby sustaining cardiomyocyte function and delaying cellular senescence. Our research identifies 4'-Methoxy-3', 5,7-trihydroxy flavanone as a potential small-molecule activator of CISD1, offering a promising pharmacological approach to modulate mitochondrial dynamics in aging cardiomyocytes. By directly addressing the mechanistic link between CISD1, mitochondrial stability, and telomere preservation, this research bridges a critical gap in understanding age-related cardiomyopathy and provides a foundation for targeted therapeutic interventions. Our findings suggest that CISD1 activation could restore cellular homeostasis in aged cardiac tissues, reducing the risk of heart failure and other aging-related cardiovascular diseases. These insights advance age-related disease intervention strategies by targeting fundamental molecular pathways involved in cardiomyocyte aging.