Blame Our Evolutionary Risk of Cancer on Our Body MassDecember 06, 2006A 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." Up until now, scientists assumed that mice could afford to express telomerase, and thereby benefit from its curative powers, because their natural risk of developing cancer is low-they simply die before there's much likelihood of one of their cells becoming cancerous. "Most people don't know that if you put mice in a cage so the cat can't eat them, 90 percent of them will die of cancer," says Gorbunova. Evolution, it seems, has determined which species are allowed to express telomerase in their somatic cells in order to maintain a delicate balance between cells that live long, and cells that become cancerous. But while most scientists believed an organism's lifespan determined whether it was at a higher risk of cancer, Gorbunova has revealed evidence that it is not our long lifespan that puts us at risk, but our much-heavier-than-a-mouse body mass. The tips of chromosomes, called telomeres, shorten every time a cell divides. After about 60 divisions, the telomeres are eroded away to the point that the cell stops dividing. Telomerase rebuilds those tips, so animals that express it, like mice, have cells that can reproduce more extensively and thus heal better. Cancer cells, however, are those cells that constantly reproduce unchecked, and so evolution has shut off the expression of telomerase in human somatic cells, presumably because the threat of cancer outweighs the benefits of quick-healing. But no one has looked into why mice express telomerase and humans don't. In fact, telomerase activity has been barely catalogued in the animal kingdom. Gorbunova decided to take on the question by creating a unique test. She investigated 15 rodents from across the globe to determine what level of telomerase activity each species expressed, to see if there were some correlation she could find. The species ranged from tiny field mice to the 100-pound capybara from Brazil. Lifespans ranged from three years for the mice, to 23 or more for common backyard squirrels. Acquiring specimens of these animals from around the world proved to be an unusual task. "At one point I was woken up at two in the morning by a guy on a cell phone hunting pest beavers in Montezuma," says Gorbunova. "I'm still trying to wake up and this voice says, 'I hear you're looking for beavers.' " 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. 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. 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." As for the tiny mice: "They don't have to worry about cancer," she says. "They're probably all praying for an anti-cat gene." The University of Rochester |
|||||||||||||||||||||
| Related Telomerase Current Events and Telomerase News Articles Mice regain ability to extend telomeres suggesting potential for dyskeratosis congenita therapy The human genetic disease dyskeratosis congenita (DKC) is an autosomal dominant disease that leads to abnormalities in tissues with a rapid cell turnover - the skin, nails, bone marrow, lungs and gut. National Science Foundation congratulates Nobel Laureates in medicine/physiology, chemistry and economics The National Science Foundation (NSF) congratulates the 2009 Nobel laureates, particularly those who have received NSF funding over the years: Jack W. Szostak, who shared the prize in physiology or medicine; Thomas A. Steitz, who shared the prize in chemistry; and Elinor Ostrom and Oliver E. Williamson who earned the Sveriges Riksbank Prize in economic sciences in memory of Alfred Nobel 2009. Researchers examine mechanisms that help cancer cells proliferate A process that limits the number of times a cell divides works much differently than had been thought, opening the door to potential new anticancer therapies, researchers at UT Southwestern Medical Center report in the Aug. 7 issue of the journal Cell. Handle with care: Telomeres resemble DNA fragile sites Telomeres, the repetitive sequences of DNA at the ends of linear chromosomes, have an important function: They protect vulnerable chromosome ends from molecular attack. Variations in 5 genes raise risk for most common brain tumors Common genetic variations spread across five genes raise a person's risk of developing the most frequent type of brain tumor, an international research team reports online in Nature Genetics. Immune cells from patients with rheumatoid arthritis have prematurely aged chromosomes Telomeres, structures that cap the ends of cells' chromosomes, grow shorter with each round of cell division unless a specialized enzyme replenishes them. Maintaining telomeres is thought to be important for healthy aging and cancer prevention. Testes stem cell can change into other body tissues, Stanford/UCSF study shows Scientists at the Stanford University School of Medicine and at UC-San Francisco have succeeded in isolating stem cells from human testes. UT Southwestern researchers identify gene linked to inherited form of fatal lung disease Researchers at UT Southwestern Medical Center have determined that a mutation in a gene known for its role in defending the lungs against invading pathogens is responsible for some inherited cases of a lethal lung disease affecting older adults. The same mutation may also be associated with lung cancer, the researchers said. Researchers use chemical from medicinal plants to fight HIV Like other kinds of cells, immune cells lose the ability to divide as they age because a part of their chromosomes known as a telomere becomes progressively shorter with cell division. As a result, the cell changes in many ways, and its disease fighting ability is compromised. Scientists identify possible cause of endometriosis Endometriosis is a condition whereby patches of the inner lining of the womb appear in parts of the body other than the womb cavity. It can cause severe pain and affects approximately 15% of women of reproductive age. Endometriosis is also associated with infertility, with 50% of infertile women affected by the condition. More Telomerase Current Events and Telomerase News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||