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

Download

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

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

180
views

130
downloads

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

Suggestions

OpenMETU
Core

MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain Somel, Mehmet; Fu, Ning; Yan, Zheng; Hu, Hai Yang; Xu, Ying; Yuan, Yuan; Ning, Zhibin; Hu, Yuhui; Menzel, Corinna; Hu, Hao; Lachmann, Michael; Zeng, Rong; Chen, Wei; Khaitovich, Philipp (2010-09-01) Changes in gene expression levels determine differentiation of tissues involved in development and are associated with functional decline in aging. Although development is tightly regulated, the transition between development and aging, as well as regulation of post-developmental changes, are not well understood. Here, we measured messenger RNA (mRNA), microRNA (miRNA), and protein expression in the prefrontal cortex of humans and rhesus macaques over the species' life spans. We find that few gene expressio...
Transcriptomic network analysis of brain aging and alzheimers disease Parvizi, Poorya; Somel, Mehmet; Tunçbağ, Nurcan; Department of Biology (2017) Multiple studies have investigated aging brain transcriptomes to identify for age-dependent expression changes and determine genes that may participate in age-related dysfunction. However, aging is a highly complex and heterogeneous process where multiple genes contribute at different levels depending on individuals’ environments and genotypes. Both this biological heterogeneity of aging, as well as technical biases and weaknesses inherent to transcriptome measurements, limit the information gained from a s...
Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity İzgi, Hamit; Han, Dingding; Isildak, Ulas; Huang, Shuyun; Kocabiyik, Ece; Khaitovich, Philipp; Somel, Mehmet; Dönertaş, Handan Melike (2022-01-01) Developmental trajectories of gene expression may reverse in their direction during ageing, a phenomenon previously linked to cellular identity loss. Our analysis of cerebral cortex, lung, liver and muscle transcriptomes of 16 mice, covering development and ageing intervals, revealed widespread but tissue-specific ageing-associated expression reversals. Cumulatively, these reversals create a unique phenomenon: mammalian tissue transcriptomes diverge from each other during postnatal development, but during a...
MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates Somel, Mehmet; Tang, Lin; Yan, Zheng; Hu, Haiyang; Guo, Song; Jiang, Xi; Zhang, Xiaoyu; Xu, Guohua; Xie, Gangcai; Li, Na; Hu, Yuhui; Chen, Wei; Paeaebo, Svante; Khaitovich, Philipp (2011-12-01) While multiple studies have reported the accelerated evolution of brain gene expression in the human lineage, the mechanisms underlying such changes are unknown. Here, we address this issue from a developmental perspective, by analyzing mRNA and microRNA (miRNA) expression in two brain regions within macaques, chimpanzees, and humans throughout their lifespan. We find that constitutive gene expression divergence (species differences independent of age) is comparable between humans and chimpanzees. However, ...
Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways. KHURANA, V; et. al. (2017-02-22) Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (alpha-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact alpha-syn toxicity. To "humanize'' this molecular network, we developed a computational method, Transpose Net. This integrates a Steiner prize-collecting approach w...

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.