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Major shifts in glial regional identity are a transcriptional hallmark of human brain aging
journal contributionposted on 2020-10-20, 10:41 authored by Lilach Soreq, UK Brain Expression Consortium, North American Brain Expression Consortium, Jamie Rose, Eyal Soreq, John Hardy, Daniah Trabzuni, Mark R Cookson, Colin Smith, Mina Ryten, Rickie Patani, Jernej Ule
Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.
RNA-seqagingbrainexon microarraysgene expressionimmunohistochemistrymachine learningmicroglianeuronsolgiodendrocytesAdolescentAdultAgedAged, 80 and overAgingBrainCell CountGene Expression ProfilingGene Expression Regulation, DevelopmentalHumansMicrogliaMiddle AgedNeurogliaNeuronsOligodendrogliaOrgan SpecificityTranscription, GeneticUp-RegulationYoung AdultUK Brain Expression ConsortiumNorth American Brain Expression ConsortiumUle - secPatani - sec0601 Biochemistry and Cell Biology