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DNA damage and ageing: new-age ideas for an age-old problem

Abstract

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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Figure 1: Schematic representation of 'stochastic damage' and the connection with ageing and longevity assurance mechanisms.

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Acknowledgements

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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Correspondence to Jan H.J. Hoeijmakers.

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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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