Abstract

Ischemic stroke is associated with aging. It is possible to predict chronological age by measuring age-related changes in DNA methylation from multiple CpG sites across the genome, known as biological age. The difference between biological age and actual chronological age would indicate an individual's level of aging. Our aim was to determine the biological age of ischemic stroke patients and compare their aging with controls of the same chronological age. A total of 123 individuals, 41 controls and 82 patients with ischemic stroke were paired by chronological age, ranging from 39 to 82 years. Illumina HumanMethylation450 BeadChip array was used to measure DNA methylation in CpG sites in both groups, and biological age was estimated using methylation values of specific CpGs. Ischemic stroke patients were biologically an average 2.5 years older than healthy controls (p-value=0.010). Stratified by age tertiles, younger stroke patients (≤57 years old) were biologically older than controls (OR=1.19; 95%CI 1.00-1.41, p-value=0.046). The older groups showed no biological age differences between cases and controls, but were close to reaching the significance level. Ischemic stroke patients are biologically older than controls. Biological age should be considered as a potential new biomarker of stroke risk.

Highlights

  • Ischemic stroke (IS) is a complex age-related disease with high mortality and long-term disability

  • We examined a cohort of 123 individuals, 41 controls and 82 patients with IS, matched by chronological age

  • This is likely because this method is constructed on the basis of DNA methylation data from whole blood, like our data, while the Horvath method is constructed on a range of different tissues and cell types [11]

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Summary

Introduction

Ischemic stroke (IS) is a complex age-related disease with high mortality and long-term disability. Despite current attention to risk factors and preventive treatment, the number of stroke cases has risen in recent decades, likely because the aging population has increased. Stroke pathogenesis involves a number of different disease processes as well as interactions between environmental, vascular, systemic, genetic, and central nervous system factors [1]. 10% of IS occurs in individuals younger than 50 years, which is called “young stroke” [4,5]. This increase is often attributed to a high prevalence of unusual, rare conditions or to nontraditional risk factors such as migraine, illicit drug use, oral contraceptives, pregnancy and patent foramen oval. Stroke remains associated with the traditional risk factors: hypertension, hypercholesterolemia, diabetes mellitus, and obesity [6]

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