Understanding the “caps” on the ends of chromosomes may soon translate to understanding cancer, lung diseases, and even normal aging.

Question: What are some practical applications of your telomere discovery?

Carol Greider: Well, it turns out that there are really two different areas in which the ability of cells to divide have medical implications. And one is in cancer, where a cancer cell has to divide many, many more times than any of the normal tissue surrounding it. And so the cancer cells have to solve this telomere problem, or the telomeres will shorten and the cells won't divide. And the other area is normal cells in the body which have to do with tissue renewal. So tissue-specific stem cells where—for instance, in your blood the cells need to be able to divide every day to provide new blood cells, because the blood cells only have a very short lifespan. And so it turns out that there are a number of degenerative diseases that are typically associated with aging because the cells have gone through so many rounds of cell division. If they have short telomeres, then there are problems with tissue renewal. So the degenerative diseases of aging and cancer really are the same kind of question of how many times cells can divide.

Question: Will the discovery have anti-aging applications even for healthy patients?

Carol Greider: Yeah, I think that the interest in this age-related disease isn't just limited to certain families where they have short telomeres due to mutations in telomerase. That's where they have been studied, as well as we've studied them in mice which we create that have short telomeres. But the implication is that all individuals, when the telomeres get short, will have a certain risk associated of these age-related degenerative diseases. And it's not limited to just a subset of patients with particular mutations, but rather pointing out a general risk of these degenerative diseases in the whole population.

Question: What other medical mysteries might your research illuminate?

Carol Greider: Well, I think that we're just really trying to understand the role of telomeres in these diseases, and the spectrum of the different kinds of diseases that short telomeres may play a role in, and down the road whether or not there would be some way to have a therapeutic intervention in these diseases. They're really devastating diseases: bone marrow failure and lung diseases. And so if there were some way to intervene and change the process so that the telomeres don't shorten progressively or don't shorten as rapidly, then perhaps there would be therapeutic approaches for these diseases. So going in that direction in terms of the therapeutics, but also I think the work that has been done has opened up many more questions than it really has answered. The number of questions that have to do with how telomere length equilibrium is maintained is greater today than when we started back in the 1980s. What we discovered was the enzyme telomerase that has to provide the raw material to make telomeres longer. But how is that process regulated? There is a very, very tight equilibrium of shortening and lengthening and shortening and lengthening, and it's maintained at a very precise spot in the cell. And we would like to know, what are the molecular details that go into that? Because those molecular details will then tell us about any potential diseases in the future where the changes might lie that have to do with telomere length.

Question: How do you suspect telomere length equilibrium is maintained?

Carol Greider: I think that there are going to be multiple different layers of regulation. When the cell really cares about a process, there are always multiple different inputs and several backup mechanisms. So people are working now on the actual proteins that bind along the length of the telomere, and how those proteins then tell telomerase to elongate the telomere, and how those proteins are modified by other proteins, and I think that it's going to be a fairly complex interactive network that will take some time to tease out. But it's exciting to find out even a few of the little pieces of the puzzle.

Recorded November 10th, 2009
Interviewed by Austin Allen