Senescent cells drive increased risk of thrombosis in unstable atherosclerotic plaques

Researchers have identified how senescent cells—stressed cells that have ceased dividing but remain metabolically active—drive clot formation within atherosclerotic plaques, a central mechanism in heart attacks and strokes. The critical finding centers on loss of two regulatory proteins, LATS1 and LATS2, in endothelial cells lining blood vessels; without them, the CD38 enzyme activates abnormally, reprogramming cellular metabolism and generating chronic inflammation. Preclinical models demonstrated that CD38 overexpression not only intensifies the energy consumption of endothelial cells but destabilizes plaques and promotes thrombosis—a hybrid state where aging cells become simultaneously dysfunctional and dangerously active. Particularly relevant for those pursuing healthy life extension: inhibiting CD38 reversed these effects both in vitro and in vivo, suggesting a viable pharmacological pathway. However, parallel research indicates these same senescent cells may be structurally necessary to maintain plaque integrity, posing a therapeutic dilemma: beyond a certain point in arterial progression, intervention becomes so complex that early prevention emerges as the only rational strategy.