Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood

Abstract 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 me...

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Autores principales:	Wardah Mahmood, Lars Erichsen, Pauline Ott, Wolfgang A. Schulz, Johannes C. Fischer, Marcos J. Arauzo-Bravo, Marcelo L. Bendhack, Mohamed Hassan, Simeon Santourlidis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9945070da77641ddb99a7d48f519ce43
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spelling	oai:doaj.org-article:9945070da77641ddb99a7d48f519ce432021-12-02T13:58:15ZAging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood10.1038/s41598-020-79126-z2045-2322https://doaj.org/article/9945070da77641ddb99a7d48f519ce432020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79126-zhttps://doaj.org/toc/2045-2322Abstract 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.Wardah MahmoodLars ErichsenPauline OttWolfgang A. SchulzJohannes C. FischerMarcos J. Arauzo-BravoMarcelo L. BendhackMohamed HassanSimeon SantourlidisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wardah Mahmood Lars Erichsen Pauline Ott Wolfgang A. Schulz Johannes C. Fischer Marcos J. Arauzo-Bravo Marcelo L. Bendhack Mohamed Hassan Simeon Santourlidis Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood
description	Abstract 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	article
author	Wardah Mahmood Lars Erichsen Pauline Ott Wolfgang A. Schulz Johannes C. Fischer Marcos J. Arauzo-Bravo Marcelo L. Bendhack Mohamed Hassan Simeon Santourlidis
author_facet	Wardah Mahmood Lars Erichsen Pauline Ott Wolfgang A. Schulz Johannes C. Fischer Marcos J. Arauzo-Bravo Marcelo L. Bendhack Mohamed Hassan Simeon Santourlidis
author_sort	Wardah Mahmood
title	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_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_sort	aging-associated distinctive dna methylation changes of line-1 retrotransposons in pure cell-free dna from human blood
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/9945070da77641ddb99a7d48f519ce43
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Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood

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