Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly
Open Access
- 30 January 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 9 (1), 327
- https://doi.org/10.1038/s41467-017-02395-2
Abstract
Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageingassociated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles which increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing.This publication has 77 references indexed in Scilit:
- Tissue-specific mutation accumulation in human adult stem cells during lifeNature, 2016
- Cross-Cancer Genome-Wide Analysis of Lung, Ovary, Breast, Prostate, and Colorectal Cancer Reveals Novel Pleiotropic AssociationsCancer Research, 2016
- A global reference for human genetic variationNature, 2015
- HTSeq—a Python framework to work with high-throughput sequencing dataBioinformatics, 2014
- Age-dependent regulation of tumor-related microRNAs in the brain of the annual fish Nothobranchius furzeriMechanisms of Ageing and Development, 2012
- Emerging roles of ATF2 and the dynamic AP1 network in cancerNature Reviews Cancer, 2010
- GAGE: generally applicable gene set enrichment for pathway analysisBMC Bioinformatics, 2009
- CCAAT/enhancer-binding protein β: its role in breast cancer and associations with receptor tyrosine kinasesExpert Reviews in Molecular Medicine, 2009
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005
- Age-related differences in behavior across the life span of the C57BL/6J mouseExperimental Aging Research, 1981