TY - JOUR T1 - Reversal of ageing- and injury-induced vision loss by Tet-dependent epigenetic reprogramming JF - bioRxiv DO - 10.1101/710210 SP - 710210 AU - Yuancheng Lu AU - Anitha Krishnan AU - Benedikt Brommer AU - Xiao Tian AU - Margarita Meer AU - Daniel L. Vera AU - Chen Wang AU - Qiurui Zeng AU - Doudou Yu AU - Michael S. Bonkowski AU - Jae-Hyun Yang AU - Emma M. Hoffmann AU - Songlin Zhou AU - Ekaterina Korobkina AU - Noah Davidsohn AU - Michael B. Schultz AU - Karolina Chwalek AU - Luis A. Rajman AU - George M. Church AU - Konrad Hochedlinger AU - Vadim N. Gladyshev AU - Steve Horvath AU - Meredith S. Gregory-Ksander AU - Bruce R. Ksander AU - Zhigang He AU - David A. Sinclair Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/07/31/710210.abstract N2 - Ageing is a degenerative process leading to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise, which disrupts youthful gene expression patterns that are required for cells to function optimally and recover from damage1–3. Changes to DNA methylation patterns over time form the basis of an ‘ageing clock’4, 5, but whether old individuals retain information to reset the clock and, if so, whether this would improve tissue function is not known. Of all the tissues in the body, the central nervous system (CNS) is one of the first to lose regenerative capacity6, 7. Using the eye as a model tissue, we show that expression of Oct4, Sox2, and Klf4 genes (OSK) in mice resets youthful gene expression patterns and the DNA methylation age of retinal ganglion cells, promotes axon regeneration after optic nerve crush injury, and restores vision in a mouse model of glaucoma and in normal old mice. This process, which we call recovery of information via epigenetic reprogramming or REVIVER, requires the DNA demethylases Tet1 and Tet2, indicating that DNA methylation patterns don’t just indicate age, they participate in ageing. Thus, old tissues retain a faithful record of youthful epigenetic information that can be accessed for functional age reversal. ER -