Cellular aging is thought to be controlled, in part, by the chromosomes’ telomeres – end caps that protect our DNA. But the relationship may be much more complex than scientists thought, as new evidence suggest a mechanism for cancer to bypass aging entirely.
At the end of our chromosomes are protective caps called telomeres. These structures get shorter and shorter with each successive cell division. And when the telomeres get to a critical short length, the cell is signaled to die. In this way, telomeres act as a built-in timer for cell death.
However, in the case of cancer cells, the telomeres seem to escape the usual shortening, and cancer cells can divide past their expiry status. Thus, abnormal functioning telomeres imbue cancer its characteristic immortality.
But how do the telomeres of cancer cells, with their constant growing and dividing, not be susceptible to shortening? As it turns out, scientists at the University of Pittsburgh showed that cancer cells seem to make more of telomerase – the enzyme that lengthens telomeres.
Furthermore, the team found something startling about this process. Whereas factors, like oxidative stress, would damage DNA and shorten the telomeres, telomeres in cancer cells seemed to thrive in this condition. "Much to our surprise, telomerase could lengthen telomeres with oxidative damage," said Patricia Opresko, the study’s senior author. "In fact, the damage seems to promote telomere lengthening."
Oxidative stress also doesn’t seem to affect the process of adding building blocks on to telomeres in the same way that scientists thought. Under damaging conditions, the team found that telomerase can add damaged DNA precursor molecules to the end of the chromosomes, but was unable to add damaged DNA molecules. "We also found that oxidation of the DNA building blocks is a new way to inhibit telomerase activity, which is important because it could potentially be used to treat cancer, said Opresko.
"The new information will be useful in designing new therapies to preserve telomeres in healthy cells and ultimately help combat the effects of inflammation and aging. On the flip side, we hope to develop mechanisms to selectively deplete telomeres in cancer cells to stop them from dividing," said Dr. Opresko.
"Using this exciting new technology, we'll be able to learn a lot about what happens to telomeres when they are damaged, and how that damage is processed," she said.
Additional sources: University of Pittsburgh Schools of the Health Sciences press release, Medical Daily