Soreq, L;
UK Brain Expression Consortium, .;
North American Brain Expression Consortium, .;
Rose, J;
Soreq, E;
Hardy, J;
Trabzuni, D;
... Ule, J; + view all
(2017)
Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.
Cell Reports
, 18
(2)
pp. 557-570.
10.1016/j.celrep.2016.12.011.
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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.
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