December 11, 2006
Larger Body Size Cancer Risk Lowers Telomerase Expression

Telomerase is an enzyme that rebuilds tips of chromosomes. The tips or ends of chromosomes get shorter each time a cell divides. As humans age our chromosome tips get shorter and once they get too short our cells can not divide well. Chronic stess not coincidentally shortens telomeres and also accelerates the aging of our bodies. So why don't our bodies just make enough telomerase enzyme to rebuild our chromosome tips? Evolutionary biologists theorize that selective pressures reduced telomerase expression to reduce cancer risk.

The link between telomerase and aging makes telomerase research an interest to biologists who study aging and cancer. Vera Gorbonova decided to compare the telomerase expression in 15 rodent species from around the globe and found telomerase expression is inversely correlated with body mass.

A key enzyme that cuts short our cellular lifespan in an effort to thwart cancer has now been linked to body mass.

Until now, scientists believed that our relatively long lifespans controlled the expression of telomerase—an enzyme that can lengthen the lives of cells, but can also increase the rate of cancer.

Vera Gorbunova, assistant professor of biology at the University of Rochester, conducted a first-of-its-kind study to discover why some animals express telomerase while others, like humans, don't. The findings are reported in today's issue of Aging Cell.

"Mice express telomerase in all their cells, which helps them heal dramatically fast," says Gorbunova. "Skin lesions heal much faster in mice, and after surgery a mouse's recovery time is far shorter than a human's. It would be nice to have that healing power, but the flip side of it is runaway cell reproduction—cancer."

The activation of telomerase could help rejuvenate bodies. But telomerase activation would probably come with higher risk of cancer. We need cures for cancer not only to avoid death from cancer but also to make it easier to use stem cells and other cell types to create replacement parts. Without those replacement parts we'll die from worn out organs and work out capillaries and other parts failures even if we can avoid cancer.

Are rodent species as close to each other on the evolutionary tree as this scientist assumes? How far back did the first branching of existing rodent species occur? Anyone know?

For over a year, Gorbunova collected deceased rodents from around the world and had them shipped to her lab in chilled containers. She analyzed their tissues to determine if the telomerase was fully active in them, as it was in mice, or suppressed, as it is in humans. Rodents are close to each other on the evolutionary tree and so if there were a pattern to the telomerase expression, she should be able to spot it there.

To her surprise, she found no correlation between telomerase and longevity. The great monkey wrench in that theory was the common gray squirrel, which lives an amazing two decades, yet also expresses telomerase in great quantity. Evolution clearly didn't see long life in a squirrel to be an increased risk for cancer.

I am guessing she was expecting to find an inverse correlation between telomerase expression and longevity. Shorter lived species ought to be able to allow greater repair by turning up telomerase since shorter lived species will die from other things before cancer.

But that line of thinking does not make sense anyway since we know short lived mice die from cancer. Their cells deterioriate and they lose control of them more quickly. Do their cells mutate more rapidly than human cells? I dimly recall that mice or rats have DNA polymerase enzymes that make errors at higher rates than human DNA polymerase.

Bigger bodies mean more cells which mean more risk of a cell mutating into cancers. So it is not surprising to me that bigger body rodents have less telomerase.

Body mass, however, showed a clear correlation across the 15 species. The capybara, nearly the size of a grown human, was not expressing telomerase, suggesting evolution was willing to forgo the benefits in order to reign in cancer.

The results cannot be directly related to humans, but Gorbunova set up the study to produce very strong across-the-board indicators. It's clear that evolution has found that the length of time an organism is alive has little effect on how likely some of its cells might mutate into cancer. Instead, simply having more cells in your body does raise the specter of cancer—and does so enough that the benefits of telomerase expression, such as fast healing, weren't worth the cancer risk.

One reason why the results do not directly relate to humans: We may have evolved better mechanisms for controlling cancer. Or maybe the rodents evolved better mechanisms to control cancer. But I would also expect rodents to differ between species in the quality of their mechanisms for doing cell replication and in their immune mechanisms for stopping cancer.

Larger animals have even larger numbers of cells and therefore, all else equal, even greater chances of developing cancer. Every additional cell is an additional risk for cancer. So the bigger an organism gets the greater the need to develop additional methods to control cancer.

Gorbunova points out that these findings raise another, perhaps far more important question: What, then, does this mean for animals that are far larger than humans? If a 160-pound human must give up telomerase to thwart cancer, then what does a 250,000-pound whale have to do to keep its risk of cancer at bay?

"It may be that whales have a cancer suppressant that we've never considered," says Gorbunova. "I'd like to find out what kind of telomerase expression they have, and find out what else they use to combat cancer."

We might eventually find genetic mechanisms for cancer prevention in other species that we could adapt to humans. Genes transferred from other species into human stems cells could serve to make youthful replacement organs less prone to become cancerous.

Here is the abstract and link to the paper.

Share |      Randall Parker, 2006 December 11 04:01 PM  Aging Mechanisms

Dan said at December 15, 2006 8:19 AM:

How do whales prevent cancer? They live underwater. It's hard to smoke there.

John said at August 19, 2008 12:03 AM:

Perhaps the answer lies in the more advanced immune systems of the larger creates, verses the higher metabolic rates and cell replacement of the smaller creatures.

Ebbe Lundsgaard said at May 17, 2010 6:20 PM:

Read my article on web: 'Cancer - Tamlin group'.

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