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Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood
LINE-1 hypomethylation of cell-free DNA has been described as an epigenetic biomarker of human aging. However, in the past, insufficient differentiation between cellular and cell-free DNA may have confounded analyses of genome-wide methylation levels in aging cells. Here we present a new methodologi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746734/ https://www.ncbi.nlm.nih.gov/pubmed/33335196 http://dx.doi.org/10.1038/s41598-020-79126-z |
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author | Mahmood, Wardah Erichsen, Lars Ott, Pauline Schulz, Wolfgang A. Fischer, Johannes C. Arauzo-Bravo, Marcos J. Bendhack, Marcelo L. Hassan, Mohamed Santourlidis, Simeon |
author_facet | Mahmood, Wardah Erichsen, Lars Ott, Pauline Schulz, Wolfgang A. Fischer, Johannes C. Arauzo-Bravo, Marcos J. Bendhack, Marcelo L. Hassan, Mohamed Santourlidis, Simeon |
author_sort | Mahmood, Wardah |
collection | PubMed |
description | LINE-1 hypomethylation of cell-free DNA has been described as an epigenetic biomarker of human aging. However, in the past, insufficient differentiation between cellular and cell-free DNA may have confounded analyses of genome-wide methylation levels in aging cells. Here we present a new methodological strategy to properly and unambiguously extract DNA methylation patterns of repetitive, as well as single genetic loci from pure cell-free DNA from peripheral blood. Since this nucleic acid fraction originates mainly in apoptotic, senescent and cancerous cells, this approach allows efficient analysis of aged and cancerous cell-specific DNA methylation patterns for diagnostic and prognostic purposes. Using this methodology, we observe a significant age-associated erosion of LINE-1 methylation in cfDNA suggesting that the threshold of hypomethylation sufficient for relevant LINE-1 activation and consequential harmful retrotransposition might be reached at higher age. We speculate that this process might contribute to making aging the main risk factor for many cancers. |
format | Online Article Text |
id | pubmed-7746734 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77467342020-12-18 Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood Mahmood, Wardah Erichsen, Lars Ott, Pauline Schulz, Wolfgang A. Fischer, Johannes C. Arauzo-Bravo, Marcos J. Bendhack, Marcelo L. Hassan, Mohamed Santourlidis, Simeon Sci Rep Article LINE-1 hypomethylation of cell-free DNA has been described as an epigenetic biomarker of human aging. However, in the past, insufficient differentiation between cellular and cell-free DNA may have confounded analyses of genome-wide methylation levels in aging cells. Here we present a new methodological strategy to properly and unambiguously extract DNA methylation patterns of repetitive, as well as single genetic loci from pure cell-free DNA from peripheral blood. Since this nucleic acid fraction originates mainly in apoptotic, senescent and cancerous cells, this approach allows efficient analysis of aged and cancerous cell-specific DNA methylation patterns for diagnostic and prognostic purposes. Using this methodology, we observe a significant age-associated erosion of LINE-1 methylation in cfDNA suggesting that the threshold of hypomethylation sufficient for relevant LINE-1 activation and consequential harmful retrotransposition might be reached at higher age. We speculate that this process might contribute to making aging the main risk factor for many cancers. Nature Publishing Group UK 2020-12-17 /pmc/articles/PMC7746734/ /pubmed/33335196 http://dx.doi.org/10.1038/s41598-020-79126-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mahmood, Wardah Erichsen, Lars Ott, Pauline Schulz, Wolfgang A. Fischer, Johannes C. Arauzo-Bravo, Marcos J. Bendhack, Marcelo L. Hassan, Mohamed Santourlidis, Simeon Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood |
title | Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood |
title_full | Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood |
title_fullStr | Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood |
title_full_unstemmed | Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood |
title_short | Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood |
title_sort | aging-associated distinctive dna methylation changes of line-1 retrotransposons in pure cell-free dna from human blood |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746734/ https://www.ncbi.nlm.nih.gov/pubmed/33335196 http://dx.doi.org/10.1038/s41598-020-79126-z |
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