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Nat Commun. 2018 Jan 30;9(1):327. doi: 10.1038/s41467-017-02395-2.

Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.

Author information

1
Research Group Medical Systems Biology, Institute of Experimental Medicine, Christian-Albrechts-University Kiel, D-24105, Kiel, Germany.
2
Jena University Language and Information Engineering Lab, Friedrich-Schiller-University Jena, D-07743, Jena, Germany.
3
GerontoSys JenAge Consortium, D-07745, Jena, Germany.
4
Genome Analysis Lab, Leibniz Institute on Aging-Fritz-Lipmann-Institute, D-07745, Jena, Germany.
5
Hans Berger Department of Neurology, Jena University Hospital, D-07747, Jena, Germany.
6
Systems Biology and Bioinformatics Group, Leibniz Institute for Natural Product Research and Infection Biology-Hans-Knöll-Institute, D-07745, Jena, Germany.
7
Biology of Ageing Lab, Leibniz Institute on Aging-Fritz-Lipmann-Institute, D-07745, Jena, Germany.
8
Molecular Genetics Lab, Leibniz Institute on Aging-Fritz-Lipmann-Institute, D-07745, Jena, Germany.
9
Imageing Facility, Leibniz Institute on Aging-Fritz-Lipmann-Institute, D-07745, Jena, Germany.
10
Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, D-07747, Jena, Germany.
11
Network Modeling, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, D-07745, Jena, Germany.
12
Institute for Medical Informatics and Statistics, Christian-Albrechts-University Kiel, D-24105, Kiel, Germany.
13
Energy Metabolism Laboratory, Swiss Federal Institute of Technology (ETH) Zurich, Schwerzenbach/Zürich, CH-8603, Switzerland.
14
Department of Bioinformatics, Friedrich-Schiller-University Jena, D-07743, Jena, Germany.
15
Laboratory of Neurobiology, Scuola Normale Superiore, University of Pisa, I-56100, Pisa, Italy.
16
Molecular Biology Lab, Leibniz Institute on Aging-Fritz-Lipmann-Institute, D-07745, Jena, Germany.
17
Faculty of Biology and Pharmacy, Friedrich-Schiller-University Jena, D-07743, Jena, Germany.
18
Biocomputing Lab, Leibniz Institute on Aging-Fritz-Lipmann-Institute, D-07745, Jena, Germany.
19
Department of Computer Science and Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, 20742, USA.
20
Research Group Medical Systems Biology, Institute of Experimental Medicine, Christian-Albrechts-University Kiel, D-24105, Kiel, Germany. c.kaleta@iem.uni-kiel.de.
21
GerontoSys JenAge Consortium, D-07745, Jena, Germany. c.kaleta@iem.uni-kiel.de.

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 ageing-associated 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.

PMID:
29382830
PMCID:
PMC5790807
DOI:
10.1038/s41467-017-02395-2
[Indexed for MEDLINE]
Free PMC Article

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