Nature 448, 375-379 (19 July 2007) | doi:10.1038/nature05949; Received 21 March 2007; Accepted 22 May 2007

Delayed ageing through damage protection by the Arf/p53 pathway

Ander Matheu1,5,6, Antonio Maraver1,5, Peter Klatt1, Ignacio Flores2, Isabel Garcia-Cao1, Consuelo Borras3,6, Juana M. Flores4, Jose Viña3, Maria A. Blasco2 & Manuel Serrano1

  1. Tumor Suppression Group,
  2. Telomeres and Telomerase Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain
  3. Department of Physiology, University of Valencia, Valencia 46010, Spain
  4. Department of Animal Surgery and Medicine, Complutense University of Madrid, Madrid 28040, Spain
  5. These authors contributed equally to this work.
  6. Present address: Division of Stem Cell and Developmental Genetics, MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK (A.M.); Catholic University of Valencia, 94 Guillem de Castro Street, Valencia 46003, Spain (C.B.).

Correspondence to: Manuel Serrano1 Correspondence and requests for materials should be addressed to M.S. (Email: mserrano@cnio.es).

The tumour-suppressor pathway formed by the alternative reading frame protein of the Cdkn2a locus (Arf) and by p53 (also called Trp53) plays a central part in the detection and elimination of cellular damage, and this constitutes the basis of its potent cancer protection activity1, 2. Similar to cancer, ageing also results from the accumulation of damage and, therefore, we have reasoned that Arf/p53 could have anti-ageing activity by alleviating the load of age-associated damage. Here we show that genetically manipulated mice with increased, but otherwise normally regulated, levels of Arf and p53 present strong cancer resistance and have decreased levels of ageing-associated damage. These observations extend the protective role of Arf/p53 to ageing, revealing a previously unknown anti-ageing mechanism and providing a rationale for the co-evolution of cancer resistance and longevity.


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