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

Dönertaş, Handan Melike; İzgi, Hamit; Kamacıoğlu, Altuğ; He, Zhisong; Khaitovich, Philipp; Somel, Mehmet

doi:10.1038/s41598-017-05927-4

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

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Khaitovich, Philipp
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Citation

Dönertaş, H. M., İzgi, H., Kamacıoğlu, A., He, Z., Khaitovich, P., & Somel, M. (2017). Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity. Scientific Reports, 7(1): 5894. doi:10.1038/s41598-017-05927-4.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-B0D4-0

Abstract

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.