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

• Main Authors: Wardah Mahmood, Lars Erichsen, Pauline Ott, Wolfgang A. Schulz, Johannes C. Fischer, Marcos J. Arauzo-Bravo, Marcelo L. Bendhack, Mohamed Hassan, Simeon Santourlidis
• Format: Article
• Language: English
• Published: Nature Publishing Group 2020-12-01
• Series: Scientific Reports
• Online Access: https://doi.org/10.1038/s41598-020-79126-z

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.