The immortality enzyme? Telomerase fights aging, fuels cancer

Investigating a powerful target for extending lifespans — and suppressing tumor growth.
Written by: Matt Windsor
Media contact: Yvonne Taunton

Tollefsbol 700Trygve Tollefsbol is a renowned expert on telomerase, an enzyme that plays crucial roles in determining our lifespans and fueling cancer growth.In a lab in the heart of Campbell Hall, UAB biologist Trygve Tollefsbol, Ph.D., D.O., stores the secret to immortality—but you may not want it.

Telomerase, the enzyme in question, is a quirky character. Even though it is dormant most of the time, it appears to play a key role in all three of Tollefsbol’s main research interests: aging, cancer, and epigenetics.

Telomerase’s job is to lengthen telomeres, little caps at the end of our chromosomes that keep the chromosomes from becoming unstable during cell division. (They’re kind of like the plastic cylinders on the ends of shoelaces, Tollefsbol says.)

But a little bit gets shaved off with each cycle of division. Eventually, there is very little protective telomere left, and cells age and stop dividing.

Immortal Cells—With a Twist

“We can make cells live forever in our lab by giving them telomerase,” Tollefsbol says. But don’t book your next 200 vacations just yet. “Being able to do things at a cellular level and for a whole organism are two entirely different things,” Tollefsbol cautions. His lab continues to investigate telomerase as a potential way to extend lifespans. But strangely enough, they’re working to eliminate telomerase as well.

There’s a wrinkle in the telomerase story: “Most cancer cells are addicted to it,” says Tollefsbol, who is a senior scientist in the UAB Comprehensive Cancer Center. “They have to have their telomeres maintained to keep replicating. Telomerase doesn’t cause cancer itself, but most cancer cells can’t be cancer cells without telomerase.” That’s what allows them to keep growing.

In fact, 90 percent of cancers are fueled by telomerase, Tollefsbol explains. “And the more malignant the cancer, the higher the telomerase expression. Some people believe that aging is just a tumor-suppression mechanism—we down-regulate telomerase so we will not be as susceptible to cancer.”

Several research groups, including Tollefsbol’s, are trying to find ways to selectively target the telomerase in cancer cells. (He recently co-edited a book on the topic with his wife, UAB researcher Lucy Andrews, Ph.D.) His team has had some success in inserting “RNA interference” sequences into telomerase genes that tag the enzyme for destruction by the cell’s repair mechanisms.

They are also looking into the process that allows normal cells to turn telomerase back on. But Tollefsbol is also exploring ways to “get ahead of the curve”; that is, to prevent the tumors from forming in the first place.

Food Finds

Tollefsbol is particularly interested in sulforaphane—“a major active component of cruciferous vegetables” such as broccoli, cabbage, cauliflower, and kale—and green tea polyphenols. “We’ve discovered that many of these dietary compounds can prevent the telomerase gene from being activated,” Tollefsbol says. “We’re very excited about this, because it suggests that if one eats the right diet during their life that they may be able to keep telomerase from becoming active, which would lower the risk of cells becoming cancer cells.”

These compounds seem to control telomerase through epigenetic means—that is, by altering the chemical markers on the telomerase gene to stop the enzyme from being produced. (In the late 1990s, Tollefsbol and Andrews were the first to propose that telomerase is under epigenetic control, publishing their hypothesis in a theoretical journal. “We were right, fortunately,” he says.)

Tollefsbol recently received a $1.5-million grant from the National Institutes of Health to investigate the cancer-fighting effects of a combination of broccoli sprouts and green tea polyphenols.

Tollefsbol says his lab has already worked out what appear to be the optimal concentrations of these foods in a diet. For green tea, “generally it’s about two to five cups per day, depending on the size of the person,” Tollefsbol says. For the cruciferous vegetables, “it’s about a cup a day,” he says. “It seems that this could be incorporated worldwide and affect hundreds of thousands, if not millions, of people.”

What if you don’t like broccoli? “Usually what I recommend is using some low-calorie sauce, such as soy sauce, to make it taste better,” he says. And it’s better to eat the whole food than take a supplement, he notes. “We find that whole foods tend to be much more effective, because there’s a synergy between the many different compounds in the whole foods.”