Introduction by Dan Eden

In a previous article I wrote about the reason that we get old, worn out and eventually die. It has to do with a material that grows on each end of our DNA molecule. Called a "telomere" this substance has no apparent reason for existing but to provide a kind of blank leader -- like the blank film on n old movie -- that protected the vital DNA code each time it made a copy of itself.

If we could only prevent the telomere from wearing down and shortening -- exposing the vital DNA to errors of replication -- then we could be "immortal!"

While scientists have learned how to save and restore telomeres, there was another problem. If cells like cancer could do this then there was no way to stop their growth. Eventually the "immortal" cancer cells would take over and we would die from that, rather than from old age.

Studies with different chemicals have been conducted to determine how to prolong telomeres while preventing cancer cells from growing. These studies are usually conducted on rats. One such study revealed something totally amazing.

Over the last three years, Gorbunova and Andrei Seluanov, research professor of biology at the University of Rochester, have worked to understand the similarities and differences of how varied but closely related species of rats deal with cancer. When Gorbunova and her team began investigating mole rat cells, they were surprised at how difficult it was to grow the cells in the lab for study.

The mole rat cells simply refused to replicate once a certain number of them occupied a space in the petri dish. Other cells, such as human cells, also cease replication when their populations become too dense, but the mole rat cells were reaching their limit much earlier than other animals' cells. Why?

Naked mole rats are strange, ugly, nearly hairless mouse-like creatures that live in underground communities. Unlike any other mammal, these communities consist of queens and workers more reminiscent of bees than rodents. Naked mole rats can live up to 30 years, which is exceptionally long for a small rodent. Despite large numbers of naked mole-rats under observation, there has never been a single recorded case of a mole rat contracting cancer. Adding to their mystery is the fact that mole rats appear to age very little until the very end of their lives.-- Gorbunova.

Until Gorbunova and Seluanov's research, the prevailing wisdom had assumed that an animal that lived as long as we humans do needed to suppress the telomere activity to guard against cancer. Telomeres help cells reproduce, and cancer is essentially runaway cellular reproduction. An animal living for 70 years has a lot of chances for its cells to mutate into cancer.

In 2006, Gorbunova made the surprising discovery that telomerase -- the enzyme that makes up the telomeres -- is highly active in small rodents like the mole rat.

Gorbunova points out that a rat's life expectancy is often shortened by other factors in nature, such as accidents or being hunted. Since old age was not to be the likely end of the rats nature had afford them the slim cancer risk in exchange for the active telomeres ability to speed healing. The trade-off made sense.

But the fact that mole rats can live so long with no sign of cancer wasn't fitting this model. Something else was preventing the cells, with prolonged telomeres, from becoming cancerous.

"Since cancer is basically runaway cell replication, we realized that whatever was doing this was probably the same thing that prevented cancer from ever getting started in the mole rats," says Gorbunova.

The special gene

Now, Gorbunova believes she has found the primary reason these small animals are staying cancer-free, and it appears to be a kind of overcrowding early-warning gene that the naked mole rat expresses in its cells.

The findings, presented in The Proceedings of the National Academy of Sciences, show that the mole rat's cells express a gene called p16 that makes the cells "claustrophobic," stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. This is why the cells refused to grow beyond a certain density in the petri dish.

The effect of p16 is so pronounced that when researchers purposely mutated the cells to induce a tumor, the cells' growth barely changed, whereas regular mouse cells became fully cancerous.

Double barrier

Like many animals, including humans, the mole rats have a gene called p27 that prevents cellular overcrowding, but the mole rats use another, earlier defense in gene p16. Cancer cells tend to find ways around p27, but mole rats have a double barrier that a cell must overcome before it can grow uncontrollably.

"We believe the additional layer of protection conferred by this two-tiered contact inhibition contributes to the remarkable tumor resistance of the naked mole rat," says Gorbunova in the PNAS paper.

Gorbunova and Seluanov are now planning to delve deeper into the mole rat's genetics to see if their cancer resistance might be applicable to humans.

This research was funded by the National Institutes of Health and the Ellison Medical Foundation.

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