The journal club is back for December and we will be discussing the new Sinclair lab paper where researchers have successfully rejuvenated the eyes of aged mice using cellular reprogramming. As some additional background, we recently covered the paper in an article on the news outlet which you can find here.
Join us December 22nd at 12:00 pm Eastern / 5 pm UK time live on our Facebook page.
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 TET. 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.
You can find the research paper here.
Lu, Y., Brommer, B., Tian, X., Krishnan, A., Meer, M., Wang, C., … & Yang, J. H. (2020). Reprogramming to recover youthful epigenetic information and restore vision. Nature, 588(7836), 124-129.