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There is growing evidence that exercise is a powerful physiological intervention that can obviously enhance cell rejuvenate capacity, but its molecular mechanisms that mediate the axonal regenerative benefits remain largely unclear. Using the eye as the CNS model, here it is first indicated that placing mice in an exercise stimulation environment induced DNA methylation patterns and transcriptomes of retinal ganglion cell, promoted axon regeneration after injury, and reversed vision loss in aged mice. These beneficial effects are dependent on the DNA demethylases TET3\u2010mediated epigenetic effects, which increased the expression of genes associated with the regenerative growth programs, such as STAT3, Wnt5a, Klf6. Exercise training also shows with the improved mitochondrial and metabolic dysfunction in retinas and optic nerves via TET3. Collectively, these results suggested that the increased regenerative capacity induced by enhancing physical activity is mediated through epigenetic reprogramming in mouse model of optic nerve injury and in aged mouse. Understanding the molecular mechanism underlying exercise\u2010dependent neuronal plasticity led to the identification of novel targets for ameliorating pathologies associated with etiologically diverse diseases.<\/jats:p>","DOI":"10.1002\/adbi.202400145","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T07:00:54Z","timestamp":1721026854000},"source":"Crossref","is-referenced-by-count":4,"title":["TET3 Contributes to Exercise\u2010Induced Functional Axon Regeneration and Visual Restoration"],"prefix":"10.1002","volume":"9","author":[{"given":"Si","family":"Fang","sequence":"first","affiliation":[{"name":"Multiscale Research Institute of Complex Systems, Department of Integrative Oncology in Fudan University Shanghai Cancer Center, Jingan District Central Hospital of Shanghai, Department of Otorhinolaryngology\u2010Head and Neck Surgery in Huashan Hospital Fudan University Shanghai 200433 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