Behind the Study is a series of transcribed videos from researchers elaborating on their recent oncology-focused studies published by Aging. A new Behind the Study is released each Monday. Visit the Aging YouTube channel for more insights from outstanding authors.
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Dr. Marina Antoch
My name is Marina Antoch, and I am a member of Department of Pharmacology and Therapeutics for Roswell Park Cancer Institute, and actually working here at Roswell for 10 years now. Recently my group, in collaboration with few other laboratories and the local biotech startup company, Everon Biosciences, summarized the recent research in the paper that was published in the journal, Aging. This paper is related to working out a novel approach that will allow us to assess the overall health in the preclinical animal model organelle.
Working with the company that’s really interested in developing some therapeutics that could combat aging, slow down aging, we really need to get some quantitative tools that we can use to assess the efficacy of those molecules of those potential drugs that they identify in their preclinical studies. There were few works that would suggest some approaches how we can do that, but none of these really satisfy the goals that we have.
So we have to think of some other approaches that we may use, and there were several requirements that we really need for developing the successful protocols. First of all, we wanted this protocol to be absolutely non-invasive for our preclinical animal models, so it could be repeated on the same subject for several times. We can actually look through the lifespan of the subject, how these parameters and overall health is changed with age. They have to be really quantitative. So we didn’t really want to rely on some observational things like the hair grain, for example, that’s been considered the hallmark of aging for many years. Many of these observations, they really require coring by several individual observers and then they are compared, and they’re very subjective. (We) really wanted to get something more objective that we could put in numbers.
This manuscript that was published actually summarized almost three-year work that was dedicated to this problem. We tried many different approaches and finally came up with a protocol that we called determining physiological frailty index. And this frailty index is just the cumulative estimate of many, many physiological parameters that are related to the health of the animal. And they’re very relevant to human studies since these such parameters as body weight or physical strength that we could measure, usually using special equipment or blood pressure that we can measure in animal models-very similar to how we do it in humans, blood cell parameters, and a few others that can really give us the quantitative assessment of each parameter. Then we compare how much it is in older animals – or in animals that don’t feel well. How much of these parameters differ from when compared to the younger animals, and that gave us a certain quantitative estimate. So why is that important? It’s important for the reason of testing, as I mentioned already, various potential biologicals that would be developed as anti-aging drugs.
This protocol will now allow us to assess, quantitatively, the health status of animals then treat them with potential therapeutics, and then down the road, repeat this measurement to see if this frailty index, brought any improvement or not, and that would be indicative of the efficacy of the therapy. So this is one of the major goals of our research and why we developed this protocol. But for all future studies, we have actually another thought in mind, how we may use this particular approach. We’re now related to cancer research as you may know, due to the really successful development of many anti-cancer drugs, and many anti-cancer therapies. There are more and more cancer survivors. Actually in 2016, the American Cancer Society published statistics saying that there’s about 15 million people that went through the very harsh chemotherapeutic and radiation therapies. They are cancer-free. They never had relapsed cancer, but these therapies definitely affect a lot of other aspects of their health. And one of those aspects, besides any specific diseases, that they may develop is the accelerated aging.
With the development of more and more therapeutics, the expectation is that in 2026, there’ll be more than 20 million of cancer survivors. We’ll really need to be thinking about developing novel cancer therapeutics. We really should think not to make them more efficient and less toxic, but also to be able to diminish their damaging effect down the road at the latest stages of the life of basically to improve the quality of life of cancer survivors by adjusting the treatments at the time that we treat cancer. So we have less problems later on. To do that first, we have to test this in our preclinical models and for success of those tests, we really needed some quantitative assay that we can apply.
We think that our protocol of physiological frailty index would serve this purpose very well. So, basically, testing the efficacy and the therapeutic efficacy of different chemotherapeutic drugs. We may also look on a long-term effects to see how that affects animals health and adjust treatments based on the preclinical evaluation. This is why we think it’s really an important tool that could be very useful in many aspects of preclinical studies, and maybe sometimes applied then as many of preclinical studies translated into the clinical applications.
I’m also thinking that it may be very relevant for treatment of childhood cancers. Childhood cancers are very specific type of cancers. First of all, the regiments are actually the same as are worked out for adult people. Although young people and adult people are very different physiologically. They’re just adjusted by the weight, the age a little bit. But in principle, they are about the same.
The rate of cure for some types of childhood cancers nowadays is also pretty sufficient. So there is a large population of kids that went through chemotherapy and radiation that was applied to a very critical moment in their development. So they are effective. It’s really very significant. Actually the longevity of those childhood cancer survivors is statistically lower and they will premature age and develop a lot of different complications. So I think that that could be particularly important for treating various types of childhood cancers, and that can really affect the way we are treating childhood malignancies.
If we are able to reach our goal and adjust the treatment so we’re focusing not only on immediate therapeutic effect, but take into account these long-term complications that would inevitably arise after the treatment, we can significantly improve the quality of life of cancer survivors. That would be a very significant impact on the overall health of the population, I would say.
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