lso shows the supercentenarian as a DNA methylome outlier (Fig. 3e). Importantly, because the loss of DNA methylation in repetitive sequences has been reported through the aging process42, we carefully studied the DNA methylation content of
bioRxiv preprint doi: https://doi.org/10.1101/2025.02.24.639740; this version posted February 25, 2025. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license.
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three families of repeats: LINE-1, ALU and ERV. Interestingly, we found that the supercentenarian did not undergo major hypomethylation events in these loci, instead retained hypermethylated CpGs even at higher levels than most of the younger individuals (Fig. 3f). Thus, these findings suggest that a disruption of the DNA methylation balance (hypermethylation/hypomethylation) in gene 5’-regulatory CpG islands is linked to the aging trajectory, but keeping epigenetically silent DNA repetitive sequences could confer an advantage associated with healthy longevity, as it occurred in our case.
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