ABSTRACT NUMBER: ESOC2026A2303 SENESCENCE GENE EXPRESSION IS ASSOCIATED WITH OUTCOME IN PATIENTS WITH ISCHEMIC STROKE

Abstract Background and aims Cellular senescence increases with age. Senescent cells can contribute to age-related diseases. Senescence accumulation might affect vascular health. We sought to investigate the relationship between senescence gene expression and stroke outcome. Methods In 129 patients with acute ischemic stroke and 41 control participants, whole-blood gene expression was measured by microarray. Expression of senescence-associated genes was evaluated using single-sample gene set enrichment analysis using the SenMayo gene set. Stroke outcome was determined by stroke neurologists using the modified Rankin Scale (mRS) at 90-days after stroke onset. Results Stroke patients were divided into good (90-day mRS<2) and poor (90-day mRS>2) outcome. The stroke outcome groups showed significantly different senescence gene expression enrichment between them (p=0.030) and compared with control participants (Fig. 1A, p=0.020 for good, and p<0.001 for poor outcome). All participants were divided into age tertiles. In the 73-84 years old group, senescence gene expression was found different in patients with good (p=0.010) and poor (p=0.002) stroke outcome compared with controls. In the group >84 years, senescence enrichment in the poor outcome group was different from the good outcome group (Fig. 1B, p=0.041). Patients were classified into low or high senescence using the cohort’s median, outcome was assessed using the full mRS. High senescence was associated with a shift towards worse mRS (p=0.047) even after adjustment for sex, age, stroke severity, and diabetes. Conclusions Senescence is associated with worse stroke outcomes, potentially affecting vascular health through inflammation. Targeting senescence may offer a novel strategy to improve stroke outcome. Conflict of interest All authors: nothing to disclose. GJ receives funding from the Canadian Institutes for Health Research (CIHR), the University Hospital Foundation, Heart and Stroke Foundation, Genome Canada, and the NIH. Figure 1 - belongs to Results