Aging is a known co-morbidity of ischemic stroke with its risk and severity increasing every year past 55+. While many of the current stroke therapies have shown success in reducing mortality, post-stroke morbidity has not seen the same substantial reduction. Recently, the involvement of cellular senescence and SASP in brain injury and neurological degeneration has been recognized. Ischemic injury causes oxidative stress and mitochondrial damage that induces senescence through the activation of p21 and p16 pathways, ultimately leading to synthesis and release of senescence-associated secretory phenotype (SASP). This ischemic event causes stress-induced premature senescence (SIPS), aging the brain decades beyond the standard biological age due to an increase in senescent cells in the ischemic core and ipsilateral hemisphere. Therefore, therapies that target the senescent cells and SASP, including senolytics, senomorphic drugs, stem cell therapies, and other cell-specific interventions, may be a new path for stroke treatment.
Keywords: neuroinflammation; senescence; senescence-associated secretory phenotype; senolytics.