Major shifts in glial regional identity are a transcriptional hallmark of human brain aging
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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 UleAbstract
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.
Journal details
Journal Cell Reports
Volume 18
Issue number 2
Pages 557-570
Available online
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Publisher website (DOI) 10.1016/j.celrep.2016.12.011
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Europe PubMed Central 28076797
Pubmed 28076797
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