Aging Immune System in Acute Ischemic Stroke

Abstract

Background and Purpose: With advancing age, alterations occur to the immune system, including an increase in inflammation (inflammaging) and a reduced ability to respond to new immune challenges. The role of an aging immune system in patients with ischemic stroke remains unclear, although age is an important determinant of stroke risk and outcome. This study assessed the aging immune system in patients with acute ischemic stroke by differences in leukocyte gene expression in relationship to age. Methods: Peripheral blood RNA from 2 cohorts with acute ischemic stroke was measured by whole-genome microarray, and genes associated with advancing age were identified (false discovery rate-corrected P <0.05, partial correlation coefficient <|0.3|). Genes were characterized by pathway analysis and compared with age-associated genes from nonstroke studies (n=3974). Results: There were 166 genes associated with age in cohort 1 (derivation cohort, n=94). Sixty-nine of these age-associated genes were verified in cohort 2 (validation cohort, n=79). Identified genes included a decrease in CR2 , CD27 , CCR7 , and NT5E . Genes were associated with altered B-cell receptor signaling, lymphocyte proliferation, and leukocyte homeostasis. Forty-three of the 69 age-associated genes in stroke were also associated with age in nonstroke studies. Conclusions: A relationship between leukocyte gene expression and age in patients with ischemic stroke was identified. The changes include alterations to the adaptive humoral immune system, which may influence age-related stroke risk and outcome.

Immunosenescence and multiple sclerosis

“…Engler-Chiurazzi et al [26] found that the activation of brain-resident immune cells and peripheral immune infiltration played an important role in the poststroke acute injury phase and in the long-term recovery period. Age-related changes in leukocyte gene expression in patients with ischaemic stroke have been confirmed, and may have an influence on the risk of stroke and its outcome [25]. The risk of cancer is increased by long-lasting inflammation [27].…”

“…The elderly are also more prone to develop paraproteinemic, vasculitic and inflammatory demyelinating neuropathies, which could be related to immunosenescence [24]. Age is an important risk factor in stroke and its outcomes [25]. Engler-Chiurazzi et al [26] found that the activation of brain-resident immune cells and peripheral immune infiltration played an important role in the poststroke acute injury phase and in the long-term recovery period.…”

Sex Differences in Poststroke Inflammation: a Focus on Microglia Across the Lifespan

“…Aging by itself is associated to changes in the immune system, such as a rise in inflammatory markers and diminished response to cytokine stimulation, which can modulate the stroke progression and outcome. 70 In experimental stroke, while young females show smaller infarct volume compared with males, the outcome is inverted in aged males. 16,40,48 It is still under discussion whether the worsened outcome of aged females compared with males is caused by the lack or dysregulation of estrogens, or due to a sex chromosome-linked features.…”

Protein Biomarkers in Blood Reflect the Interrelationships Between Stroke Outcome, Inflammation, Coagulation, Adhesion, Senescence and Cancer

“…Again, there is an overlap with the biomarkers presented in this review, supporting the hypothesis that thrombotic events, including recurrent stroke, as well as sarcopenia may be triggered by post-stroke coagulation and inflammation. A recent transcriptomics analysis highlights the role of the aging immune system in acute stroke (Sykes et al 2021) and suggests that not just the inflammatory aspects of the immune system play a role in determining disease outcome. However, the functional status of the (adaptive) immune system is not as easy to measure as its contribution to inflammatory processes, explaining why no such markers are prominently reported as protein biomarkers in the blood.…”

“…Estimated by an epigenetic (DNA methylation) assay, it contributes to outcome prediction after stroke (Soriano-Tarraga et al 2021), and patients with a high biological age may be given more intensive care. Other predictors are based on gene expression (Sykes et al 2021) and protein abundance (Montellano et al 2021). Proteins are expected to be involved directly in the molecular processes that influence the outcome, so they are informative about both molecular mechanisms and intervention success rates, and therefore we focus on those in this review.…”