RETRACTED ARTICLE: Aging-associated distinctive DNA methylation changes of LINE-1 retrotransposons in pure cell-free DNA from human blood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

Retrotransposons as a Source of DNA Damage in Neurodegeneration

“…However, Sirt7 is downregulated during aging in hematopoietic stem cells ( Mohrin et al, 2015 ), suggesting that this repressive mechanism of LINE-1 could be altered. Furthermore, it has been reported that aging is correlated with the decrease of LINE-1 retrotransposon promoter methylation in purified cell-free DNA from human blood ( Mahmood et al, 2020 ).…”

Olive Oil Improves While Trans Fatty Acids Further Aggravate the Hypomethylation of LINE-1 Retrotransposon DNA in an Environmental Carcinogen Model

“…Different organs in vivo and tumor cells in vitro show various correlation patterns between their aging and the possibility of the occurrence of mutations in them [37][38][39][40]. Mahmood and coworkers have found a positive association between L1-RTP hypomethylation measured in the DNA content of the cell-free fraction of blood and aging and the increased likelihood of malignant tumorous diseases [41,42]. Interestingly, however, the correlation between aging and the probability of development of somatic mutations in the kidney renal cell carcinoma (KIRC) and the kidney renal papillary cell carcinoma (KIRP) cell lines is inverse (Horvath, 2013)-which provides a basis for studying the methylation pattern of renal DNA.…”

Promising Epigenetic Biomarkers for the Early Detection of Colorectal Cancer: A Systematic Review

“…One of CRC's characteristics is CpG island methylator phenotype (CIMP) which represents the overall hypermethylation status of specific genes that are involved in cellular growth and Long interspersed nucleotide element-1 (LINE-1) is an autonomous retrotransposon that generates new genomic insertions through the retrotransposition of an RNA intermediate. LINE-1 hypomethylation can serve as a biomarker for human aging [24,25], and is also associated with the early-onset of CRC [26]. The methylation status of DZIP3, an E3 ubiquitin ligase, appears to be the bridge between aging, the immune system, and CRC [13].…”