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ORIGINAL RESEARCH article
Front. Aging
Sec. Genetics, Genomics and Epigenomics of Aging
Volume 6 - 2025 |
doi: 10.3389/fragi.2025.1467639
This article is part of the Research Topic Epigenetic Regulation and Non-Histone Post-Translational Modification in Aging View all 3 articles
Multiplexing and massive parallel sequencing of targeted DNA methylation to predict chronological age
Provisionally accepted
Dean Li 1*
Bowen Zhu 1 Guojing Han 2* Xue Yao 3* Hongqin Gu 4* Tao Liu 4* Linghua Liu 4* Jie Dai 4* Isabella Zhaotong Liu 5* Yanlin Liang 6* Jian Zheng 7* Zheming Sun 8* He Lin 8* Nan Liu 9* Haidong Yu 4* Meifang Shi 4* Gaofang Shen 10*
Lefeng Qu 2*- 1 Interdisciplinary Research Center of Biology and Chemistry, Shanghai, China
- 2 Department of Vascular and Endovascular Surgery, Shanghai Changzheng Hospital, Shanghai, China
- 3 Technology Department of Haidian Sub-bureau, Beijing Public Security Bureau, Beijing, China
- 4 Youyi Road Community Health Service Centre for Baoshan District, Shanghai, China
- 5 Shanghai American School, Shanghai, China
- 6 Forensic Science Institute of Shanghai Public Security Bureau, Shanghai, China
- 7 Institute of Criminal Science and Technology Shanghai Xuhui Public Security Sub-bureau, Shanghai, China
- 8 Third Research Institute of Ministry of Public Security, Beijing, China
- 9 Interdisciplinary Research Center on Biology and Chemistry (CAS), Shanghai, China
- 10 Institute of Criminal Science and Technology of Criminal Police Detachment，Yangzhou Public Security Bureau, Yangzhou, China
Estimation of chronological age is particularly informative in forensic contexts. Assessment of DNA methylation status allows for the prediction of age, though the accuracy may vary across models. In this study, we started with a carefully designed discovery cohort with more elderly subjects than other age categories, to diminish the effect of epigenetic drifting. We applied multiplexing and massive parallel sequencing of targeted DNA methylation, which let us to construct a model comprising 25 CpG sites with substantially improved accuracy (MAE=2.279, R=0.920). This model is further validated by an independent cohort (MAE=2.204, 82.7% success (±5 years)). Remarkably, in a multi-center test using trace blood samples from forensic caseworks, the correct predictions (±5 years) are 91.7%. The nature of our analytical pipeline can easily be scaled up with low cost. Taken together, we propose a new age-prediction model featuring accuracy, sensitivity, high-throughput, and low cost. This model can be readily applied in both classic and newly emergent forensic contexts that require age estimation .
Keywords: DNA Methylation, age-prediction model, multiplexing, Massive parallel sequencing, Targeted region
Received: 20 Jul 2024; Accepted: 04 Feb 2025.
Copyright: © 2025 Li, Zhu, Han, Yao, Gu, Liu, Liu, Dai, Liu, Liang, Zheng, Sun, Lin, Liu, Yu, Shi, Shen and Qu. 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:
Dean Li, Interdisciplinary Research Center of Biology and Chemistry, Shanghai, China
Guojing Han, Department of Vascular and Endovascular Surgery, Shanghai Changzheng Hospital, Shanghai, China
Xue Yao, Technology Department of Haidian Sub-bureau, Beijing Public Security Bureau, Beijing, China
Hongqin Gu, Youyi Road Community Health Service Centre for Baoshan District, Shanghai, China
Tao Liu, Youyi Road Community Health Service Centre for Baoshan District, Shanghai, China
Linghua Liu, Youyi Road Community Health Service Centre for Baoshan District, Shanghai, China
Jie Dai, Youyi Road Community Health Service Centre for Baoshan District, Shanghai, China
Isabella Zhaotong Liu, Shanghai American School, Shanghai, China
Yanlin Liang, Forensic Science Institute of Shanghai Public Security Bureau, Shanghai, China
Jian Zheng, Institute of Criminal Science and Technology Shanghai Xuhui Public Security Sub-bureau, Shanghai, China
Zheming Sun, Third Research Institute of Ministry of Public Security, Beijing, China
He Lin, Third Research Institute of Ministry of Public Security, Beijing, China
Nan Liu, Interdisciplinary Research Center on Biology and Chemistry (CAS), Shanghai, China
Haidong Yu, Youyi Road Community Health Service Centre for Baoshan District, Shanghai, China
Meifang Shi, Youyi Road Community Health Service Centre for Baoshan District, Shanghai, China
Gaofang Shen, Institute of Criminal Science and Technology of Criminal Police Detachment，Yangzhou Public Security Bureau, Yangzhou, China
Lefeng Qu, Department of Vascular and Endovascular Surgery, Shanghai Changzheng Hospital, Shanghai, China
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