With each issue, Trib+Health brings you an interview with experts on issues related to health care. Here is this week's subject:
Randy Strong is a professor of pharmacology at the University of Texas Health Science Center at San Antonio. He earned his Ph.D. from the University of Texas Graduate School of Biomedical Sciences at Houston. He is a member of the Sam and Ann Barshop Institute for Longevity and Aging Studies and the Geriatric, Education and Clinical Center of the South Texas Veterans Health Care System, Audie L. Murphy Division in San Antonio. He is director of the National Institute on Aging-funded San Antonio Nathan Shock Center of Excellence in the Biology of Aging and director of the NIA-funded Aging Interventions Testing Center, where he researches aging-delaying compounds.
Editor's note: This interview has been edited for length and clarity.
Trib+Health: How did your research about compounds that can delay aging come about?
Randy Strong: Our biggest program is from the intervention testing program that the National Institute on Aging established and is funding. We are one of three centers that test for compounds for their ability to extend life span or health span. All this is done in genetically heterogeneous mice. That is to mimic the human condition, and also to prevent us from getting results that are due to something idiosyncratic about an inbred mice strain that might respond differently than other mouse strains.
Over the last 80 years, we’ve known that it is possible to intervene in the aging process. It was discovered years ago that the dietary restriction of rodents makes them live longer. Particularly when the intervention is started early in life, the rodents are smaller and they have fewer diseases and develop disease later in their life span.
This was basically the major finding that provided the impetus for this program, but in addition, there are also people who have used genetics in animals to explore different biochemical pathways in the animals that might cause them to have longer life spans. That tells you there are specific targets in the animal that actually control the rate of aging.
We started looking for compounds about 10 years ago. In 2009, we published the first paper showing that a drug, rapamycin, which was discovered as an anti-fungal agent produced by soil bacteria on Easter Island, later on, was being used to prevent rejection of kidney transplants and other transplanted tissue. That was one of the drugs we tested, and it produced a rather remarkable and rapid increase in life span even when it was started in old age. We published this in the journal Nature, and that same year, the journal Science cited our work as one of the the top 10 breakthroughs of 2009.
One of the things that is very exciting is that the larger community of people doing geriatric and gerontology research are now trying to plan clinical trials to look at these compounds coming out of our program to see if they actually can delay aging or increase health span in humans. I participated in two different conferences since last June where we discussed what it will take to get these studies started.
Trib+Health: Is that still in the talking phase or is it moving forward?
Strong: There is at least one small pilot study that has been done here at the UT Health Science Center. They gave rapamycin to elderly veterans. And while this was not a well-powered study, some of the results appeared promising. For instance, their walking speed improved. That study is still ongoing.
Trib+Health: How are researchers studying aging coming together in San Antonio?
Strong: What we do as scientists is collaborate. These collaborations usually work out because people recognize that other people are doing things that are related to what they are doing.
Another researcher, Suzette Tardif, decided to test the rapamycin in marmosets. She’s been working for the last several years to develop the marmoset as an aging model because it is a non-human primate. So it is much more closely related to humans than mice are, but the life span of a marmoset is much shorter than other non-human primates. So you can actually do an aging study within a five-year span, which is about the duration of a grant.
What Suzette has done is she has done the initial studies to show that you can intervene with rapamycin in these animals and established all of the criteria needed: the blood levels, evidence that the compound is actually doing something biological. She was evaluating it for whether it was producing any toxic side effects in monkeys, and found that it is perfectly safe to give it to these animals.
I think the next step is going to be doing an aging study to see if rapamycin increases life span in a non-human primate. That would give more rationale for doing these studies in humans.
Trib+Health: What is the potential impact if this compound is successful?
Strong: There is a lot of different manipulations now, genetic and dietary restrictions that show that when you do extend life span with one of these manipulations, that reduces a host of age-related diseases like delaying the onset of cancer. We know in mice studies that rapamycin reduces Alzheimer's pathology in mice that are bred with human genes that cause Alzheimer's disease. There is a whole host of different diseases that are delayed or even prevented because of these life-extending manipulations.
So this is really a new way of looking at how to attack the treatment of diseases such as cancer, heart disease, Type 2 diabetes. That is the concept. In a way, it is much more cost effective because we are treating aging as the therapeutic agent, and the result is that you prevent all these other diseases. These animals are not just getting older and remaining sicker longer. You’re not just extending their misery. Actually, these animals are much more healthy and active at an old age.
The drug that we are finding may not necessarily be the ones that end up being used in trying to treat age-related diseases, but they provide new tools for us to be able to dissect the pathways and the mechanism that are involved in the aging process.