Abstract / Summary
Abstract Accelerated cardiac ageing has emerged as a prominent long term complication of SARS CoV 2 infection, yet the molecular mechanism driving this phenomenon remains unknown. Here, we propose a unified mechanistic model demonstrating that COVID 19 disrupts a p53 dependent microRNA based longevity network essential for maintaining cardiac structural and immune homeostasis. SARS CoV 2 suppresses miR 145—a direct transcriptional target of p53¹—and induces the ageing associated long non coding RNA PVT1². Loss of miR 145 derepresses c Myc, elevates PVT1, and suppresses miR 23a and miR 15b 5p³, two microRNAs that restrain IL 11 and IL 33 signalling⁴. This shift activates an IL 11→IL 33→HMGB1/TLR4 inflammatory cascade that mirrors molecular signatures of cardiac ageing⁴. IL 33 drives lymphatic endothelial cell death and lymphatic rarefaction⁵, impairing lymphatic drainage and promoting persistent myocardial edema, immune infiltration, thrombosis⁶, and chronic cardiac inflammation. Together, these findings provide the first mechanistic explanation for accelerated cardiac ageing in COVID 19 survivors and position p53 as a master longevity gene whose regulatory network protects cardiac lymphatic and neurovascular integrity. This conceptual framework identifies multiple therapeutic nodes—including miR 145 restoration, PVT1 inhibition, and IL 11/IL 33 blockade—that may mitigate long term cardiovascular sequelae of SARS CoV 2 infection.