Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity

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10.1038-s41598-017-05927-4.pdf

Date

2017-07-19

Author

Donertas, Handan Melike
İzgi, Hamit
Kamacioglu, Altug
He, Zhisong
Khaitovich, Philipp
Somel, Mehmet

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It was previously reported that mRNA expression levels in the prefrontal cortex at old age start to resemble pre-adult levels. Such expression reversals could imply loss of cellular identity in the aging brain, and provide a link between aging-related molecular changes and functional decline. Here we analyzed 19 brain transcriptome age-series datasets, comprising 17 diverse brain regions, to investigate the ubiquity and functional properties of expression reversal in the human brain. Across all 19 datasets, 25 genes were consistently up-regulated during postnatal development and down-regulated in aging, displaying an "up-down" pattern that was significant as determined by random permutations. In addition, 113 biological processes, including neuronal and synaptic functions, were consistently associated with genes showing an up-down tendency among all datasets. Genes up-regulated during in vitro neuronal differentiation also displayed a tendency for up-down reversal, although at levels comparable to other genes. We argue that reversals may not represent aging-related neuronal loss. Instead, expression reversals may be associated with aging-related accumulation of stochastic effects that lead to loss of functional and structural identity in neurons.

Subject Keywords

Tool, Link, Dynamics, Synapses, Aleimers-disease, Prefrontal cortex, RNA-SEQ, Transcriptome, Neurons

URI

https://hdl.handle.net/11511/37195

Journal

SCIENTIFIC REPORTS

DOI

https://doi.org/10.1038/s41598-017-05927-4

Collections

Department of Biology, Article

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Citation Formats

H. M. Donertas, H. İzgi, A. Kamacioglu, Z. He, P. Khaitovich, and M. Somel, “Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity,” SCIENTIFIC REPORTS, pp. 0–0, 2017, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/37195.