Doxorubicin (Doxo), a widely used chemotherapy drug, causes significant aortic stiffening—a key precursor to cardiovascular disease in cancer survivors. This study in p16-3MR mice found that Doxo-induced aortic stiffening is driven by excess cellular senescence and its inflammatory secretions (SASP). Clearing senescent cells genetically (via ganciclovir) or pharmacologically (via senolytic ABT263) completely prevented aortic stiffening. Plasma from Doxo-treated mice stiffened healthy donor aortas ex vivo, an effect blocked when plasma came from senolytic-treated animals. Glycation stress—specifically via the AGE-RAGE signaling axis—emerged as a key downstream mechanism. These findings identify senolytic therapy as a promising strategy to protect cardiovascular health in chemotherapy recipients.
