The journal Nature has published the results of a collaborative study carried out by three Spanish research teams which reveal that specific mechanisms conferring protection against cancer and those that protect us against ageing are related.
The study was coordinated by Dr. Manuel Serrano, and involved the participation of two Spanish research groups: Dr. Maria A. Blasco and Dr. Jose Vina, both experts in the analysis of ageing factors.
Cancer is a disease which increases in frequency as age progresses; a characteristic which had led to the suspicion of a correlation between cancer process and ageing.
In addressing the highlight of this study; Dr. Serrano states: “we know that many of the genes protecting us from cancer act as a rigorous cellular quality control agent, ensuring the self elimination of deteriorating cells - a marvellous system avoiding cancer progression. Based on the hypothesis that ageing is due to the accumulation of deteriorating cells, we deduced that those genes protecting us from cancer should also protect us from ageing.”
Dr. Serrano’s group has been generating for years now a series of genetically modified mice endowed with an increased cancer protection potential.
These mice, or as they call “super-mice”, have demonstrated increased resistance to cancer. "Once increased cancer-resistance mice were obtained, we found ourselves in an ideal situation to examine how cancer resistance affected ageing, the only requirement was patience, lots of patience!,” says Ander Matheu, an investigator of Dr. Serrano’s group and co-author of the article.
Researchers observed that ageing was delayed when compared to normal mice in their most cancer-resistant mice generated, dubbed super-Arf/p53 mice. Such as humans, mice also have a duplicate copy of each gene (each copy inherited from a progenitor).
Researchers at the CNIO modified super-Arf/p53 mice so that they contain three copies of both Arf and p53 genes, rendering the super-Arf/p53 mice more resistant to cancer.
"We observed that super-Arf/p53 mice lived 16% longer than normal mice, and we have been able to demonstrate that decreased cancer processes was not the only reason leading to their increased longevity, since examining various indicators demonstrated that these mice do indeed age at a decreased rate,” observed Antonio Maraver, CNIO investigator involved in ageing analysis. The range of these ageing indicators varies from behavioral trials, such as observing their sense of balance, to analyzing molecular markers.
The search for p53 stimulating drugs is not a novel topic in the pharmaceutical industry. “There are several promising leads" states Dr. Serrano. The discovery published in Nature by the Spanish researchers suggests that a hypothetical drug stimulating p53, would lead not only to cancer protection, but also to increased longevity.
Dr. Serrano also added a word of caution: “excessive stimulation of p53 can be toxic, and it is possible that only a slim opportunity exists between the beneficial effects against cancer and ageing and its possible harmful effects, requiring further research which only time will tell. In any case, I am confident that this discovery has opened a gateway which will lead to successive breakthroughs”.
DNA damage is a key cause of both cancer and ageing. It is known that the proteins Arf and p53 protect against cancer since both proteins can signal DNA lesions and remove damaged cells that might evolve into tumours. We have demonstrated that Arf and p53 are also capable of constraining the accumulation of damaged cells during the ageing processes. Therefore, Arf and p53 act simultaneously against cancer and against ageing.