Every Thursday, Laboratory Equipment features a Scientist of the Week, chosen from the science industry’s latest headlines. This week’s scientist is Dr. Ronald DePinho from the Dana Farber Cancer Institute. DePinho and his team partially reversed age-related degeneration in mice, resulting in new growth of the brain and testes, improved fertility and the return of a lost cognitive function.
Q: How did you come to focus on the telomerase enzyme in relation to aging?
A: Our lab working in cancer genetics and the most important risk factor for cancer is advanced aging, sow we wanted to better understand age and development of cancer in humans. Humans typically get epithelial cancers which makes up about 85 percent of cancers. We thought telomerase might be important for a different number of reasons. We started studying it in the mid-1990s and found that mice had longer and a more promiscuous expression of telomerase than humans. We thought that might account for species difference between mouse, who get cancers like lymphoma most often, opposite of epithelial cancers in humans.
We collaborated to knock out telomerase, and we generated mice that now could experience telomerase dysfunction. We made them shorter like in human cells, and the cancer threat shifted toward epithelial cancer. This was an insight into a link between telomerase and cancer. And that is how we then got into the aging work.
Q: What do you see as an immediate impact of your research? What about further down the road?
A: I think this research as illuminated a path to thinking about regenerative medicine in a slightly different way. It teaches us that aged tissue, even degenerative ones, have a capacity to retain if you remove the underlying cause. In this case, the cause was excessive telomerase damage and DNA damage, which is a major cause of aging in mice and humans. The next step is to understand how tissues retain the capacity to regenerate. I think it will help motivated many to understandhow to better regulate telomerase. Although years and decades away, I think pharmaceutical interventions can be done to restore telomerase and maintain tissues health. They contribute a lot to againg. We have found that shorter telomerase is linked to an increased risk of cancer, cardiovascular disease and Alzheimer’s in humans over the age of 60.
Q: What was the most surprising thing you found in your research?
A: The way we did it was to engineer mice that could flip telomerase on and off. In the off position, we saw advanced aging prematurely. We saw smaller brains, gray hair, impaired cognition and infertility. When we turned it back on, we were expecting stabilization or even a slowing of the againg process, but instead we saw a dramatic reversal of the signs and symptoms of aging. It was the first time age has been revered in an animal. It teaches us aging can be reversed if the underlying cause is removed.
Q: What is the take home message of your research and results?
A: Our message is that aging is a complex compress, btu there are important factors and roles for telomerase in this process. It is important to emphasize that telomerase is one of several, but information from these and human studies say telomerase is an important contributor.
It is important to understand there is a lot you can do now for healthy living. Excessive DNA damage accelerate aging, and it is increase in those who suffer from obesity, unmanaged diabetes, don’t exercise and those who smoke. You can increase years of healthy living by exercising, eating right and not smoking. Those are important to avoiding disease and maintaining a healthy living in years.
Q: What is next for you and your research?
A: We want to better understand the specific ways in which tissue can regenerate themselves. Is it that reserves are reawakened, or committed cells are able to differentiate? We need to understand the very basic process of how tissue can regenerate.