advertisement
Abstract #90866 Published in IGR 21-4
Reprogramming to recover youthful epigenetic information and restore vision
Lu Y; Brommer B; Tian X; Krishnan A; Meer M; Wang C; Vera DL; Zeng Q; Yu D; Bonkowski MS; Yang JH; Zhou S; Hoffmann EM; Karg MM; Schultz MB; Kane AE; Davidsohn N; Korobkina E; Chwalek K; Rajman LA; Church GM; Hochedlinger K; Gladyshev VN; Horvath S; Levine ME; Gregory-Ksander MS; Ksander BR; He Z; Sinclair DANature 2020; 588: 124-129
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 DNA methylation patterns over time form the basis of ageing clocks, 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 (CNS) loses function and regenerative capacity. Using the eye as a model CNS 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 DNA 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 DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.
Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA.
Full articleClassification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
11.9 Gene therapy (Part of: 11 Medical treatment)
