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
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 expression changes are unique to aging. Instead, the vast majority of miRNA and gene expression changes that occur in aging represent reversals or extensions of developmental patterns. Surprisingly, many gene expression changes previously attributed to aging, such as down-regulation of neural genes, initiate in early childhood. Our results indicate that miRNA and transcription factors regulate not only developmental but also post-developmental expression changes, with a number of regulatory processes continuing throughout the entire life span. Differential evolutionary conservation of the corresponding genomic regions implies that these regulatory processes, although beneficial in development, might be detrimental in aging. These results suggest a direct link between developmental regulation and expression changes taking place in aging.


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...
Meta analysis of alzheimer’s disease at the gene expression level
İzgi, Hamit; Somel, Mehmet; Department of Biology (2017)
In this study, publicly available microarray gene expression datasets are used to investigate common gene expression changes in different postmortem brain regions in Alzheimer’s Disease (AD) patients compared to control subjects, and to find possible functional associations related to these changes. The hypothesis is that pathogenesis of the disease converges into common patterns of dysregulation/alteration or dysfunction in molecular pathways across different brain regions in AD. In total, I studied 13 dat...
Gene expression reversal toward pre-adult levels in the aging human brain and age-related loss of cellular identity
Donertas, Handan Melike; İzgi, Hamit; Kamacioglu, Altug; He, Zhisong; Khaitovich, Philipp; Somel, Mehmet (2017-07-19)
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,...
Evaluation of methylation profiles of an epidermal growth factor receptor gene in a head and neck squamous cell carcinoma patient group
Mutlu, M.; Mutlu, Pelin; Azarkan, S.; Baylr, Ö.; Öcal, B.; Saylam, G.; KORKMAZ, MEHMET HAKAN (2021-03-23)
Upregulation of the epidermal growth factor receptor (EGFR) gene has shown an important impact on the development of head and neck cancers due to its important regulation role on multiple cell signaling pathways. The aim of this study was to investigate the methylation pattern of the promoter region of the EGFR gene between head and neck squamous cell carcinoma (HNSCC) patients and a control group. Forty-seven unrelated HNSCC patients, clinically diagnosed at the Department of Otorhinolaryngology, Dlşkapl Y...
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...
Citation Formats
M. Somel et al., “MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain,” GENOME RESEARCH, pp. 1207–1218, 2010, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/41164.