Arf, Arf for super-p53

The tumour suppressor protein p53 and one of its regulators, Arf, are known to be involved in the detection and elimination of cellular damage, the basis of the pathway's potent cancer prevention activity.

As with cancer, ageing also results from the accumulation of damage. A Spanish research team, led by Manuel Serrano from the Spanish National Cancer Research Centre in Madrid, speculated that the combination of p53 and Arf could have anti-ageing activity as well as cancer-prevention activity by decreasing age-related damage.

In a paper published in Nature this week, the team provides evidence that genetically manipulating mice by boosting endogenous Arf/p53 activity provides a robust anti-oxidant effect that not only suppresses cancers, but also delays ageing.

"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," the researchers say.

The team crossed two sets of mice, one set with a single extra gene-dose of p53 and the other with Arf - referred to as super-p53 and super-Arf mice.

The team knew that super-p53 mice had an identical survival period to wild-type mice, while super-Arf mice showed a modest increase in survival.

The combination of super-Arf and super-p53, however, showed a significantly extended longevity period - in fact, there was an increase in median lifespan of 16 per cent.

They also found that various biological and molecular markers of ageing indicated that these mice stay younger for longer.

"We propose that the spectra of genes activated by p53 under normal physiological conditions have a global anti-oxidant effect, thus decreasing ageing-associated oxidative damage," they write.

Delayed ageing through damage protection by the Arf/p53 pathway is published in the July 19 issue of Nature.