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
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 ageing, they tend to converge towards similar expression levels, a process we term Divergence followed by Convergence, or DiCo. We found that DiCo was most prevalent among tissue-specific genes and associated with loss of tissue identity, which is confirmed using data from independent mouse and human datasets. Further, using publicly available single-cell transcriptome data, we showed that DiCo could be driven both by alterations in tissue cell type composition and also by cell-autonomous expression changes within particular cell types.


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...
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,...
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...
Temporal changes in the gene expression heterogeneity during brain development and aging
Isildak, Ulas; Somel, Mehmet; Thornton, Janet M.; Donertas, Handan Melike (Springer Science and Business Media LLC, 2020-03-01)
Cells in largely non-mitotic tissues such as the brain are prone to stochastic (epi-)genetic alterations that may cause increased variability between cells and individuals over time. Although increased interindividual heterogeneity in gene expression was previously reported, whether this process starts during development or if it is restricted to the aging period has not yet been studied. The regulatory dynamics and functional significance of putative aging-related heterogeneity are also unknown. Here we ad...
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...
Citation Formats
H. İzgi et al., “Inter-tissue convergence of gene expression during ageing suggests age-related loss of tissue and cellular identity,” eLife, vol. 11, pp. 0–0, 2022, Accessed: 00, 2022. [Online]. Available: