Some cells in our bodies carry an internal fountain of youth—telomerase, an enzyme that allows cells to keep dividing virtually forever. This immortality, however, carries a steep price: cancer.

“If you over-express telomerase in mice, you get a mouse that heals very fast, which is related to aging, but you also get a mouse that generates tumors very rapidly,” says Mike Jarstfer, PhD, an assistant professor at the UNC Eshelman School of Pharmacy who is studying telomerase.

“Mortality is an evolutionary trait that protects us against cancer. So it’s a tradeoff: You can be mortal and not get cancer or be immortal and get cancer, which would kill you anyway. It’s a double-edged sword.”

Aging, in part, is the process of the body’s cells being told to stop dividing and sometimes to die. Cancer cells, on the other hand, continuously divide, not having the normal signals to stop or to die. In very simple terms, cancer cells have escaped the aging process, and telomerase could be the responsible party, Jarstfer says.

“Telomerase has generated a fair bit of interest since its discovery in the 1980s because it plays a role both in aging and in cancer,” he says. “Telomerase helps to make telomeres, which are the ends of the chromosomes.”

Frayed shoelaces

Jarstfer likens the telomeres to the plastic caps on the end of a shoelace. The cellular reproduction process can’t replicate the end of the chromosomes very well, causing the chromosomes to decay a little from the end each time they are reproduced. Telomerase replenishes the lost DNA, keeping the end from “fraying.”

“It’s a quirk in the DNA-replication mechanism,” Jarstfer says. “Telomerase overcomes the loss of DNA during each cell cycle.”

Telomerase is present in embryonic stem cells, which divide repeatedly to form the fetus. In most normal cells, the enzyme is switched off soon after birth. As we grow and age, our chromosomes literally shrink from the ends. Normal cells can only reproduce so many times before their DNA is so degraded that replication can no longer take place, and they stop dividing. We experience this as simply getting old.

Most types of cancers can turn telomerase back on. The few that don’t are much easier to treat. Jarstfer is studying how telomerase works and looking for ways to block or perturb the action of the enzyme. The National Science Foundation has awarded him a grant of $503,011 over three years for his project, “The Interaction between Telomerase and the Chromosome.”

“Even though this is basic science, we want to be able to use the information gleaned from these experiments to rationally design drug molecules to perturb telomerase function,” Jarstfer says.

“It’s an important target that is poorly understood, and learning how it functions is certainly going to facilitate the drug discovery process. Most drugs on the market today are targeting things that were discovered many, many years ago. Telomerase was first identified in the late ’80s, early ’90s. So it’s actually quite new.”

Some drug molecules and antibodies that target telomerase are already in early clinical trials, he says.

Beyond Telomerase

Jarstfer, who joined the School’s Division of Chemical Biology and Medicinal Chemistry in 2001, is also engaged in several other projects, including a collaboration with Bryan Roth,  a professor at the School, and Cort Pedersen, a professor in the Department of Psychiatry, on finding a treatment for autism.

Jarstfer is also examining the use of RNA in biotechnology for drug-related purposes. One idea involves using a module of RNA to hold a drug in an inert state during delivery. When the RNA reaches the target site, a signal triggers the release of the drug.

Jarstfer says the signal could be either something physicians can control, such as heat, or a naturally-occurring phenomenon in the body, such as pH level (for instance, the pH level around cancer cells is lower than around other cells).

Jarstfer is also conducting research into micro RNAs, a class of non-coding RNAs. Unlike messenger RNAs, non-coding RNAs, which have drawn a lot of attention in recent years, don’t code for proteins.

“Instead, these are small RNAs that regulate the translation of genes, and they do that by binding to portions of the mRNA,” Jarstfer says. “We have over 500 of these things, and each of them can regulate up to 100 different genes. So it turns out that there is this second layer of regulation.

“We’re looking at the role of non-coding RNAs in determining cellular lifespan. We’re looking at how the telomere length regulates micro RNA expression levels and how that correlates to whether our cells divide or not.”