The age-dependent immune response to ischemic stroke

Stroke is a devastating cause of global morbidity and mortality. Ischemic brain injury triggers a profound local and systemic immune response that participates in stroke pathophysiology. In turn, this immune response has emerged as a potential therapeutic target. In order to maximize its therapeutic potential, it is critical to understand how the immune response to ischemic brain injury is affected by age - the strongest non-modifiable risk factor for stroke. The development of multi-omics and single-cell technologies has provided a more comprehensive characterization of transcriptional and cellular changes that occur during aging. In this review, we summarize recent advances in our understanding of how age-related immune alterations shape differential stroke outcomes in older versus younger organisms, highlighting studies in both experimental mouse models and patient cohorts. Wherever possible, we emphasize outstanding questions that present important avenues for future investigation with therapeutic value for the aging population. •Omics approaches have expanded our understanding of immune aging and the immune response to ischemic stroke.•Age-related intrinsic and extrinsic changes shape the immune response to ischemic stroke.•The immune response to ischemic stroke contributes to differential outcomes in young and old hosts.•Targeting age-dependent immune alterations after ischemic stroke has therapeutic potential.