Update information. Myelin aging is a driving force of CNS aging, and age-dependent declined efficiency of remyelination caused by impaired differentiation capacity of aged oligodendrocyte precursor cell (OPC) is a major cause of demyelinated diseases. Revealing how differentiation capacity of aged OPC is affected metabolically holds the key to find new way to rejuvenate the aged OPC. Here we screened out that NAD+ is one of the top metabolites impaired in premature aging OPC. Supplementing β-nicotinamide mononucleotide (β-NMN), an immediate NAD+ precursor, delays CNS myelin aging, promotes differentiation of aged OPC, and therapeutically and preventively rejuvenates remyelination in the aged CNS both ultra-structurally and functionally. To explore the molecular mechanisms underlying the enhancing remyelination by NAD+ supplementation, using LC-MS we investigated the changes of proteome differentially regulated by NAD+ or DMSO in cultured OPC from P0 rat brain.