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

Cell Rep. 2017 Jan 10;18(2):557-570. doi: 10.1016/j.celrep.2016.12.011.


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.

Keywords: RNA-seq; aging; brain; exon microarrays; gene expression; immunohistochemistry; machine learning; microglia; neurons; olgiodendrocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Brain / metabolism*
  • Cell Count
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Humans
  • Microglia / cytology
  • Microglia / metabolism
  • Middle Aged
  • Neuroglia / cytology
  • Neuroglia / metabolism*
  • Neurons / cytology
  • Neurons / metabolism
  • Oligodendroglia / metabolism
  • Organ Specificity / genetics
  • Transcription, Genetic*
  • Up-Regulation / genetics
  • Young Adult