Reprogramming to recover youthful epigenetic information and restore vision. Reprogramming to recover youthful epigenetic information and restore vision

Epigenetic reprogramming via a combination of three Yamanaka factors, Oct4, Sox2, and Klf4 (OSK), provides an effective way to promote axon regeneration in chemical- or injury-damaged neurons and improve neuronal function in aged mice. DNA methylation landscape is remodeled during this reprogramming process. This study was designed to examine DNA methylation age in differentiated human neurons post axonal damage with or without OSK expression. Differentiated SH-SY5Y neurons were transduced with AAV.DJ vectors to induce OSK expression for five days, followed by 24-hr treatment with 100nM vincristine (VCS) to induce neurite degeneration. Neurons were harvested at either day 1 or day 9 after VCS treatment. The Illumina Infinium DNA methylation EPIC array was used to obtain DNA methylation profiles. The skin & blood clock from Horvath 2018 (PMID: 30048243 PMCID: PMC6075434) was used for DNA methylation age analysis. Overall design: The study was designed to examine DNA methylation profile of differentiated human SH-SY5Y neurons post vincristine induced axonal injury with or without OSK treatment.