ENA0000GenomicsMultiomicsBioinformatics Section, DIR IT & Bioinformatics, NINDS/NIHhttps://www.ebi.ac.uk/ena/browser/view/PRJNA278645Homo sapiensThe efficiency of central nervous system (CNS) remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study we show that expression of genes involved in the retinoid X receptor (RXR) pathway are decreased with aging in myelin-phagocytosing cells. Loss of RXR function in young macrophages mimics aging by delaying remyelination after experimentally-induced demyelination, while RXR agonists partially restore myelin debris phagocytosis in aged macrophages. The FDA-approved RXR agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in aging human monocytes to a more youthful profile. These results reveal the RXR pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics. Overall design: 24 Human CD14+ monocyte-sorted PBMC samples representing 4 Healthy Volunteers (HV) and 4 Multiple Sclerosis (MS) patients under 3 different treatment conditions. Condition 1 = (-) Phagocystosis (-) Bexarotene. Condition 2 = (+) Phagocystosis (-) Bexarotene. Condition 3 = (+) Phagocystosis (+) Bexarotene.ENASheaths, Myelin, Retinoid, Remyelinations., Myelin Sheaths, Phagocytoses, activation, Sheathhuman being, human., man0.00.00.00.00.00falseHomo sapiensRetinoid X Receptor activation reverses the age-related deficiency in myelin debris phagocytosis and enhances remyelination2022-05-122015-11-06PRJNA278645GSE66988264636759606