Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

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Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

Cell Rep. 2017 Jan 10;18(2):557-570

Authors: Soreq L, UK Brain Expression Consortium, North American Brain Expression Consortium, Rose J, Soreq E, Hardy J, Trabzuni D, Cookson MR, Smith C, Ryten M, Patani R, Ule J

Abstract
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.

PMID: 28076797 [PubMed - in process]

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