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Sci Rep. 2017 Dec 4;7(1):16890. doi: 10.1038/s41598-017-17322-0.

Transcriptomic profiling of the human brain reveals that altered synaptic gene expression is associated with chronological aging.

Author information

1
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
2
Department of Neuroscience, Karolinska Institutet, 171 77, Stockholm, Sweden.
3
Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
4
Computational Biology Core, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
5
Genetic Technologies Group, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
6
Neuromuscular disease research Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
7
Cell Biology and Gene Expression Section, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. cookson@mail.nih.gov.

Abstract

Aging is a biologically universal event, and yet the key events that drive aging are still poorly understood. One approach to generate new hypotheses about aging is to use unbiased methods to look at change across lifespan. Here, we have examined gene expression in the human dorsolateral frontal cortex using RNA- Seq to populate a whole gene co-expression network analysis. We show that modules of co-expressed genes enriched for those encoding synaptic proteins are liable to change with age. We extensively validate these age-dependent changes in gene expression across several datasets including the publically available GTEx resource which demonstrated that gene expression associations with aging vary between brain regions. We also estimated the extent to which changes in cellular composition account for age associations and find that there are independent signals for cellularity and aging. Overall, these results demonstrate that there are robust age-related alterations in gene expression in the human brain and that genes encoding for neuronal synaptic function may be particularly sensitive to the aging process.

PMID:
29203886
PMCID:
PMC5715102
DOI:
10.1038/s41598-017-17322-0
[Indexed for MEDLINE]
Free PMC Article

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