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Question: How do cells retain youthful DNA methylation pattern memory that can later on be exploited by reprogramming to abandon the old state and achieve the youthful state?
Senescence leads to several epigenetic changes in the cells. The changes can be mild enough to cause no change in function or severe enough to complete impair the functioning of the tissue. Reprogramming the cells to a previous youthful state has been an area of active research and several experiments where have shown the restoration of the youthful DNA methylation patterns of the cell during reprogramming. Reprogramming factors Oct4, Sox2, and Klf4 (OSK) promoted youthful gene expression patterns in old fibroblasts with no loss of cellular identity. In another study, four weeks of reprogramming using OSK expression significantly decreased DNA methylation age in vivo and restored youthful gene expression patterns, reversed the DNA methylation clock, and restored the function and regenerative capacity of the retina. The authors refer to this process as the recovery of information via epigenetic reprogramming or "REVIVER" for short. However, how this information is retained over the years is not known.
Lu Y, Krishnan A, Brommer B, Tian X, Meer M, Vera DL, et al. Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming. bioRxiv [Internet]. 2019; Available from: https://www.biorxiv.org/content/10.1101/710210v1