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


Peer Aramillo Irizar, Sascha Schäuble, Daniela Esser, Marco Groth, Christiane Frahm, Steffen Priebe, Mario Baumgart, Nils Hartmann, Shiva Marthandan, Uwe Menzel, Julia Müller, Silvio Schmidt, Volker Ast, Amke Caliebe, Rainer König, Michael Krawczak, Michael Ristow, Stefan Schuster, Alessandro Cellerino, Stephan Diekmann, Christoph Englert, Peter Hemmerich, Jürgen Sühnel, Reinhard Guthke, Otto W Witte, Matthias Platzer, Eytan Ruppin, Christoph Kaleta

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Nature communications

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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.

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