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Abstract
Aim: Liquid biopsies analyzing cell-free DNA (cfDNA) methylation in plasma offer a noninvasive diagnostic for diseases, with the potential of aging biomarkers underexplored. Methods: Utilizing enzymatic methyl-seq (EM-seq), this study assessed cfDNA methylation patterns in aging with blood from 35 healthy individuals. Results: It found aging signatures, including higher cfDNA levels and variations in fragment sizes, plus approximately 2000 age-related differentially methylated CpG sites. A biological age predictive model based on 48 CpG sites showed a strong correlation with chronological age, verified by two datasets. Age-specific epigenetic shifts linked to inflammation were revealed through differentially methylated regions profiling and Olink proteomics. Conclusion: These findings suggest cfDNA methylation as a potential aging biomarker and might exacerbate immunoinflammatory reactivity in older individuals.
Plain language summary
Our bodies undergo many changes as we age, some of which might affect our health. To better understand these changes, scientists study something called ‘cell-free DNA' (cfDNA) in our blood. This cfDNA can give us clues about our health and the risk of diseases like cancer or heart conditions.
In our research, we analyzed cfDNA from the blood of 35 people to identify patterns associated with aging. We discovered that approximately 2000 specific spots in our DNA change in a way that's linked to aging. These changes might help us figure out someone's biological age – essentially, how old their body seems based on various health factors, which can differ from their actual age.
We also found that these DNA changes could indicate how aging might make the body's defense system – which fights off diseases – react more intensely. Understanding this could be crucial for managing health as we get older.
Our study suggests that cfDNA could be a useful marker for aging, offering a new approach to understanding and possibly managing the health effects associated with growing older.
TWEETABLE ABSTRACT
A new study reveals cfDNA methylation in blood as a promising noninvasive marker for aging. Analysis of 35 individuals highlights key aging signatures and approximately 2000 age-related changes in DNA methylation, linking aging with inflammation. #AgingResearch #LiquidBiopsy.
First application of EM-seq for aging in healthy individuals, achieving high-quality data from limited cell-free DNA (cfDNA).
Older individuals showed increased cfDNA concentrations, suggesting higher cell turnover or death rates.
Elevated cfDNA from neutrophils and colon epithelial cells observed in older compared with younger groups.
Analysis identified around two thousand DMCs across age groups, emphasizing nucleosome structure genes.
A 48-CpG-sites cfDNA methylation model strongly correlated chronological and biological age.
Significant methylation changes, including hyper- and hypo-methylation, were detected in older individuals.
Gene promoter analysis linked increased inflammation pathways with age, supported by proteomics data.
The study highlights cfDNA methylation's potential as an aging predictive tool, especially for inflammation-related changes.
Supplemental material
Supplemental data for this article can be accessed at https://doi.org/10.1080/17501911.2024.2340958
Acknowledgments
This study was supported by the National Natural Science Foundation of China (No.82170856 and No.82304565) and the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (No. 2021-1-I2M-050).
Author contributions
J-P Cai designed the study. S-J Lia, L-T Zenga, Y-M Danga, Y-Q Maa and L-Q Zhanga collected the samples and obtained clinical data. S-J Lia, X Gao, Z-H Wanga and J Lia drafted the manuscript. S-J Lia performed bioinformatics analyses of the data. Q-Y Wanga, Y-M Zhanga, H-L Liuc, R-M Qia and J-P Cai reviewed and revised the manuscript. All authors have read and approved the final manuscript.
Competing interests disclosure
The authors declare no conflicts of interest. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Writing disclosure
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
The study was performed in accordance with the Helsinki Declaration and approved by the Ethics Committee of Beijing Hospital (reference number: 2019BJYYEC-054-02). Informed consent was obtained from all participants, and no identifying information was included in the text.
Data sharing statement
Raw data, processed data and accompanying metadata have been deposited to the Gene Expression Omnibus (GEO) database under the accession code GSE259312. The datasets generated and/or analyzed during the study are available from the corresponding author upon reasonable request.