SYSTEMATIC REVIEW article
Front. Neurol.
Sec. Neurogenetics
Accelerated biological aging based on DNA methylation clocks is a predictor of stroke occurrence: A systematic review and meta-analysis
Provisionally accepted
- 1Affiliated Hospital of Zunyi Medical University, Zunyi, China
- 2Fudan University Shanghai International Human Phenome Institutes, Shanghai, China
- 3Macao Polytechnic University, Macau, Macao, SAR China
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Background Although traditional vascular risk factors, such as hypertension and diabetes, are incorporated into stroke risk prediction models, a significant proportion of stroke events remain unexplained by these models. Increasing evidence suggests that accelerated biological aging, as measured by DNA methylation clocks, may reflect reduced organ function and heightened susceptibility to disease. However, the relationship between epigenetic age acceleration (EAA) and stroke risk remains poorly understood, with limited comprehensive synthesis of the available evidence. Methods We conducted a systematic search of PubMed, Embase, Web of Science, and Cochrane Library databases (up to January 10, 2025) for observational studies examining the relationship between DNA methylation-derived EAA and stroke risk. The study protocol was registered with PROSPERO (CRD420251010621). Results Thirteen studies met the inclusion criteria. Random-effects meta-analysis revealed a significant positive association between accelerated biological aging and stroke risk (OR= 1.16, 95% CI 1.13-1.19, I²= 98.9%, p< 0.001). Stratified analysis by stroke event demonstrated a stronger association with incident stroke (OR= 1.28, 95% CI 1.25-1.35, I²= 92.6%, p= 0.001) compared to stroke recurrence (OR= 1.11, 95% CI 1.06-1.16, I²= 63.6%, p= 0.041). Sensitivity analyses confirmed the robustness of these findings. Conclusion DNA methylation-derived measures of accelerated biological aging are robust predictors of stroke. These findings provide new insights into stroke risk assessment and emphasize potential biomarkers for early detection and prevention. Further large-scale prospective studies are needed to validate these associations and examine the role of additional modifying factors.
Keywords: DNA Methylation, Stroke, biological age, Epigenetic age acceleration, Meta-analysis
Received: 14 Jul 2025; Accepted: 27 Oct 2025.
Copyright: © 2025 Feng, Huang, Wu, Ding, Liu and DENG. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Renli DENG, 690891192@qq.com
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