Nature
Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity. Changes to deoxyribonucleic acid methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns - and, if so, whether this could improve tissue function - is not known. Over time, the central nervous system loses function and regenerative capacity. Using the eye as a model central nervous system tissue, here we show that ectopic expression of Oct4 - also known as Pou5f1, Sox2 and Klf4 genes - OSK in mouse retinal ganglion cells restores youthful deoxyribonucleic acid methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the deoxyribonucleic acid demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information - encoded in part by deoxyribonucleic acid methylation - that can be accessed to improve tissue function and promote regeneration in vivo.