Abstract WP67: Acute ischemic stroke patients with high senescence gene expression have worse outcomes.

Introduction: Senescent cells accumulate with advancing age, and exposure to cellular stressors, such as oxidative and inflammatory molecules, which can be circulating in blood. Senescent endothelial cells have altered cellular functions that may influence stroke outcomes. Studying senescence might reveal improved strategies to improve vascular health and prevent stroke or better outcomes. Hypothesis: Acute ischemic stroke patients with enriched senescence gene set expression have worse 90-day stroke outcomes. Methods: In 225 patients with acute ischemic stroke, RNA was isolated from whole blood and transcriptome measured by microarray. Enrichment of senescence genes was assessed using the SenMayo gene set in Gene Set Enrichment Analysis (GSEA). The relationship between the SenMayo senescence score and patients’ 90-day modified Rankin scale (mRS) outcome was determined. Results: SenMayo senescence genes are enriched (p=0.05) in circulation of patients of acute ischemic stroke with bad outcome (90 day mRS>2) and not in patients with good outcomes (90 day mRS≤2) (fig.1). This suggests a role for senescent cells in the pathophysiology of stroke or as a contributing factor to the failure of the patient's full recovery. Conclusion: In acute ischemic stroke patients, increased senescence gene expression is associated with worse stroke outcome. Further evaluation is needed to determine whether targeting senescence could be a strategy to improve outcome in stroke.