2078 Elimination of Senescent Cells Prevents Intracranial Aneurysm Rupture

INTRODUCTION: Clinical studies have demonstrated an association between aging and the risk of intracranial aneurysm rupture. As a result of aging, various changes in cellular homeostasis occur, including the onset of cellular senescence. Our preliminary data demonstrated the accumulation of senescent cells in human intracranial aneurysms, suggesting a potential role for cellular senescence in the pathophysiology of intracranial aneurysms. We also revealed an increase in the rupture rate of intracranial aneurysms in aged mice due to the accumulation of senescent cells. In this study, we used p16-3MR mice, which have a trimodal reporter fused to the promoter of the p16 gene, allowing the detection, isolation, and selective elimination of senescent cells. METHODS: We used both male and female p16-3MR mice at 18 months of age. We induced intracranial aneurysms by a combination of elastase injection and hypertension. After aneurysm induction, we started treatment with ganciclovir (GCV) to eliminate senescent cells or PBS as vehicle. We compared the aneurysm formation and rupture rates and the survival curve between the two groups. RESULTS: The aneurysm rupture rate was significantly lower in the GCV group than in the vehicle group in both sexes (*P<0.05). There was no statistical difference in the rate of aneurysm formation between the groups in either sex. The GCV group had a better survival rate than the vehicle group in both sexes (*P<0.05). CONCLUSIONS: Elimination of senescent cells prevents intracranial aneurysm rupture. Our results suggest that aging and senescent cells may serve as novel therapeutic targets for the prevention of aneurysm rupture.