Scientists Reverse the Aging Clock: Restore Age-Related Vision Loss Through Epigenetic Reprogramming - SciTechDaily
Harvard Medical School scientists have successfully restored vision in mice by turning back the clock on aged eye cells in the retina to recapture youthful gene function.In addition to resetting the cells’ aging clock, the researchers successfully reversed vision loss in animals with a condition mimicking human glaucoma, a leading cause of blindness around the world.The achievement represents the first successful attempt to reverse glaucoma-induced vision loss, rather than merely stem its progression, the team said.First, it promoted nerve regeneration following optic-nerve injury in mice with damaged optic nerves.
Second, it reversed vision loss in animals with a condition mimicking human glaucoma.
And third, it reversed vision loss in aging animals without glaucoma.
This theory postulates that changes to the epigenome over time cause cells to read the wrong genes and malfunction–giving rise to diseases of aging.Over time, youthful patterns of DNA methylation are lost, and genes inside cells that should be switched on get turned off and vice versa, resulting in impaired cellular function.
Yet, whether DNA methylation drives age-related changes inside cells has remained unclear.In the current study, the researchers hypothesized that if DNA methylation does, indeed, control aging, then erasing some of its footprints might reverse the age of cells inside living organisms and restore them to their earlier, more youthful state.
Lead study author, Yuancheng Lu, research fellow in genetics at HMS and a former doctoral student in Sinclair’s lab, developed a gene therapy that could safely reverse the age of cells in a living animal.In the current study, the researchers targeted cells in the central nervous system because it is the first part of body affected by aging.To test whether the regenerative capacity of young animals could be imparted to adult mice, the researchers delivered the modified three-gene combination via an AAV into retinal ganglion cells of adult mice with optic nerve injury.For the work, Lu and Sinclair partnered with Zhigang He, HMS professor of neurology and of ophthalmology at Boston Children’s Hospital, who studies optic nerve and spinal cord neuro-regeneration.The treatment resulted in a two-fold increase in the number of surviving retinal ganglion cells after the injury and a five-fold increase in nerve regrowth.Following the encouraging findings in mice with optic nerve injuries, the team partnered with colleagues at Schepens Eye Research Institute of Massachusetts Eye and Ear Bruce Ksander, HMS associate professor of ophthalmology, and Meredith Gregory-Ksander, HMS assistant professor of ophthalmology.They planned two sets of experiments: one to test whether the three-gene cocktail could restore vision loss due to glaucoma and another to see whether the approach could reverse vision loss stemming from normal aging.
Remarkably, it did so after the glaucoma-induced vision loss had already occurred.
“This new approach, which successfully reverses multiple causes of vision loss in mice without the need for a retinal transplant, represents a new treatment modality in regenerative medicine.”.
The treatment worked similarly well in elderly, 12-month-old mice with diminishing vision due to normal aging.Following treatment of the elderly mice, the gene expression patterns and electrical signals of the optic nerve cells were similar to young mice, and vision was restored.
When the researchers analyzed molecular changes in treated cells, they found reversed patterns of DNA methylation–an observation suggesting that DNA methylation is not a mere marker or a bystander in the aging process, but rather an active agent driving it.