Accelerated ageing predicts earlier onset of ischaemic stroke: a proteomic and transcriptomic investigation
European Journal of Preventive Cardiology, 2025
Quek A., Teng O., Tan T., Park J., Er B., Goh J., Jing M., Tan B., Yeo L., Chan B., Teoh H., Oh V., Lim E., Seet R.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology Aging | Pathophysiology | Plasma |  Olink Explore 3072/384 |
Abstract
Aims
The incidence of ischaemic stroke in younger adults has risen worldwide. We investigated the clinical and molecular associations of accelerated ageing in patients with ischaemic stroke.
Methods and results
Ischaemic stroke patients and community-dwelling healthy controls were recruited from the National University Hospital, Singapore, from January 2018 to December 2019. We developed models using Olink® Explore 1536 proteomic data from healthy individuals to estimate biological age, and then applied them to stroke patients. Accelerated ageing was defined as exceeding the 97.5th percentile of biological age variation in healthy controls. Next-generation RNA sequencing was performed to explore ageing-related pathways in stroke patients. Proteomic analysis of 384 age-stratified healthy controls provided biological-age estimate (R2 = 0.98, mean absolute error = 0.55 years); this model was then applied to 679 stroke patients (mean chronological age 58.7 years, 72% men). Nearly 40% of these patients exhibited accelerated ageing. Stroke occurred 8.9 years earlier in those with accelerated ageing than in those without (mean 53.4 vs. 62.3 years). Moreover, the mean biological age of 100 patients increased from 54.1 to 55.9 years 3 months post-stroke (paired t-test, P < 0.001). Among stroke patients younger than 50 years, each additional year by which biological age exceeded chronological age was associated with a 12.9% higher odds of stroke (adjusted odds ratio, 1.13; 95% confidence interval, 1.07–1.20, P < 0.001). RNA sequencing analysis revealed differential gene expression and enrichment of olfactory-signalling and sensory-perception pathways among patients with accelerated ageing.
Conclusion
Accelerated ageing is an independent risk factor for ischaemic stroke, warranting further investigation into its mechanisms to guide targeted interventions.