Loss of cell-identity DNA methylation tracks division history, not DNA damage
One influential proposal holds that DNA damage drives aging by degrading the epigenome, so that a cell loses the information that specifies what it is. We test that specific proposed driver, not the broader idea that aging involves a loss of epigenetic information. Cell-type-unique CpGs are a direct place to test it. They are the sites where a cell's methylome differs most from every other cell…
An intriguing discovery reveals that DNA methylation patterns in human skin fibroblasts effectively document a cell's division history, as opposed to the damage caused by DNA. The prevailing theory suggesting that aging results from the erosion of epigenetic information, specifically the loss of cell-type-unique methylated sites, was subjected to scrutiny.
Researchers constructed a comprehensive database of these unique sites across human skin fibroblasts, contrasting them against twenty primary cell types. The results unveiled that over 9,150 of these CpGs functioned as indicators of proliferation, rather than the specific cellular identity. These methylation patterns were shared with proliferating cell lines in culture, indicating that this layer must be distinguished from identity marks prior to evaluating the loss of identity.
Further investigation into various perturbations revealed that replication aging led to a significant 24.3% (95% CI 20.2 to 28.7) reduction in identity information, while activation of the RAS gene resulted in a mere 5.4% (4.6 to 6.1) loss. Conversely, exposure to radiation caused no discernible change in identity marks. Notably, doxorubicin-induced and irradiation-induced senescence also failed to alter the panel.
The study concluded that the loss of identity information in fibroblasts is directly correlated with prolonged cell division, rather than the immediate effects of DNA damage.
Written by urgent.news from bioRxiv's reporting — not their text. Machine-written — may contain errors; check the original before relying on it.
