When humans find the Fountain of Youth, it may ultimately come in the form of a protein shake. Researchers studying the effect of OSK, a protein cocktail of “Yamanaka factors” that converts mature cells back into embryonic stem cells, recently demonstrated that neurons can be reprogrammed to a more youthful state. This allows for improved survival and even regeneration of neurons.
The researchers injected viruses to deliver OSK into mice retinal ganglion cells (RGCs), neurons with projections from the retina that form the optic nerve. After crushing these axonal projections, they observed that axons regenerated, RGCs survived, and sight was restored with no adverse effects like tumor development. Notably, although regeneration treatment often fails in older individuals, OSK was beneficial in both younger and older mice. In addition, though no current treatment can induce regeneration after neurons sustain damage, the researchers demonstrated that OSK induction even after crush injury resulted in significant regeneration. The researchers recovered vision in mice with glaucoma, a leading cause of human blindness, as well as in mice with vision loss caused by aging. OSK expression also enhanced regrowth in human neurons in the lab.
Finally, the researchers investigated epigenetic noise, such as the change in methyl groups on DNA known as methylation. Accelerated methylation mimics aging, but OSK expression counteracted this acceleration. As additional evidence, reduction of TET enzymes that reverse methylation blocked OSK’s beneficial effects. Further research into how cells store epigenetic information will take humans closer to the reversal of aging.
Huberman, A. D. (2020). Sight restored by turning back the epigenetic clock. Nature, 588(7836), 34-36. doi:10.1038/d41586-020-03119-1
Lu, Y., Brommer, B., Tian, X. et al. Reprogramming to recover youthful epigenetic information and restore vision. Nature 588, 124–129 (2020). https://doi-org.yale.idm.oclc.org/10.1038/s41586-020-2975-4