Aging and Injured Retinal Ganglion Cells Can Be Rejuvenated by Epigenetic Reprogramming

Can aging be reversed? Scientists from Harvard Medical School were able to reverse vision loss stemming from diverse causes, such as optic nerve injury, glaucoma, and the normal aging process. The team of Bruce R. Ksander, Ph.D., reported that in vivo epigenetic reprogramming using three of the four “Yamanaka Factors” (Oct4, Sox2, and Klf4, “OSK” for short) reversed the epigenetic age of retinal ganglion cells (RGCs) in old mice based on transcriptome and DNA methylome analyses. This led to a significant improvement in visual physiology as assessed by pERG (pattern electroretinogram) and enhanced visual acuity as assessed by OMR (optomotor reflex). In addition, OSK epigenetic reprogramming restored axon regeneration following an optic nerve crush injury and improved visual function by pERG and OMR in mice with microbead-induced glaucoma (Lu, et al, Nature, 2020). This data, presented in this Journal Club, implies that the DNA methylation clock is not just a correlate of age, but a regulator of it, which also implies that old tissues retain a faithful record of youthful epigenetic information. This record can be accessed to restore or enhance tissue function and allow age reversal.