Senescent Heart Cells Drive Blood Clots and Block Their Dissolution

Thrombosis — the pathological formation of blood clots — is a leading cause of death globally, and its risk rises sharply with age. Despite this well-established epidemiological link, the precise cellular mechanisms connecting aging to clot formation have remained poorly understood. This study takes a significant step toward closing that gap.

Researchers at Ben-Gurion University of the Negev induced cellular senescence in two key cardiac cell types — cardiac fibroblasts and cardiac endothelial cells — using doxorubicin, a chemotherapy agent commonly used to model senescence experimentally. They then examined how these senescent cells influenced the coagulation cascade and fibrinolysis, the body's clot-clearing system.

The results were striking on both fronts. Senescent cardiac cells accelerated and amplified fibrinogen polymerization, the process by which soluble proteins are converted into an insoluble fibrin mesh that forms the structural backbone of a clot. Blocking thrombin — the central enzyme driving this conversion — reduced the effect, implicating thrombin overproduction as a key mechanism. Simultaneously, the senescent cells impaired fibrinolysis by suppressing plasminogen activation, meaning clots that did form were harder for the body to dissolve. Gene expression analysis confirmed upregulation of procoagulant and antifibrinolytic factors consistent with these functional observations.

Perhaps most therapeutically relevant, rapamycin — an mTOR inhibitor with established senescence-modulating properties — attenuated the senescence-driven fibrinogen polymerization in a dose-dependent manner, suggesting a potential intervention pathway.

These findings establish cellular senescence as a direct, mechanistic driver of pro-thrombotic states in cardiac tissue, not merely a bystander in aging biology. For clinicians, this raises the possibility that senostatic or senolytic therapies could reduce thrombotic risk in aging patients — a hypothesis that warrants rigorous clinical investigation.