Loss of genome maintenance may causally contribute to ageing, as exemplified by the premature appearance of multiple symptoms of ageing in a growing family of human syndromes and in mice with genetic defects in genome maintenance pathways. Recent evidence revealed a similarity between such prematurely ageing mutants and long-lived mice harbouring mutations in growth signalling pathways. At first sight this seems paradoxical as they represent both extremes of ageing yet show a similar 'survival' response that is capable of delaying age-related pathology and extending lifespan. Understanding the mechanistic basis of this response and its connection with genome maintenance would open exciting possibilities for counteracting cancer or age-related diseases, and for promoting longevity.
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This work was supported by the Netherlands Organization for Scientific Research (NWO) through the foundation of the Research Institute Diseases of the Elderly, as well as grants from SenterNovem IOP-Genomics (IGE03009), NIH (1PO1 AG17242-02), NIEHS (1UO1 ES011044), EC (QRTL-1999-02002), and the Dutch Cancer Society (EUR 99-2004).
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Garinis, G., van der Horst, G., Vijg, J. et al. DNA damage and ageing: new-age ideas for an age-old problem. Nat Cell Biol 10, 1241–1247 (2008). https://doi.org/10.1038/ncb1108-1241
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