Myelin is a multiple-layered structure formed by oligodendrocytes. The ensheathment of axons by myelin plays an important role in both functional integrity and long-term survival of axons and thus regulates activity of the central nervous system (CNS). However, with aging, some myelin sheaths exhibit myelin aging and even myelin degeneration, or demyelination, which is the key pathological feature of the autoimmune inflammatory diseases of CNS, such as multiple sclerosis (MS), and an early pathological hallmark of neurodegenerative diseases. Also, myelin repair, or remyelination, by oligodendrocytes, which are differentiated from oligodendrocyte progenitor cells (OPCs), occurs throughout life. Unfortunately, with aging, the efficiency of remyelination declines mainly due to the reduced capacity of OPC differentiation. Therefore, identifying new molecular targets in OPCs to rejuvenate the aged OPCs holds the key to promote remyelination.