Episode 73: The Science of Longevity

Episode 73: Aging with Nik Schork, Ph.D.

Karie Dozer [00:00:03] I'm Karie Dozer and this is TGen Talks. What if you could simply take a pill a once-a-day, medicine that could delay the onset of physical aging? Instead of taking a medication to lower your blood pressure or stimulate your metabolism. What if, by slowing the aging process, you could prevent those diseases that affect older people the most, like heart disease, diabetes, and cancer? In this episode, we talked to a researcher who studies the physical aging process and is a pioneer in the search for gyro protectors, substances that target the root cause of aging and age-related diseases, increasing not just our lifespan, but our health span. The quality of our years as we age. And our guest for this aging episode of Gen Talks is Dr. Nik Schork, distinguished Professor at TGen. Thanks for being here with us.

Dr. Nik Schork  [00:00:57] Yeah. No, thanks for having me. I have been around for a while now. I, graduated from the University of Michigan 30 some years ago with a PhD in quantitative genetics. So I am a quantitative biomedical researcher. Over the years, I've had appointments at Case Western Reserve University, Harvard University, University of California, San Diego, Scripps Research, and now TGen slash City of Hope.

Karie Dozer [00:01:24] And what brought you here? What were the motivating factors that got you into this area of research?

Dr. Nik Schork  [00:01:29] A great question, I mean, I've always been interested in not only quantitative aspects of science making sense of, big data sets and making mathematical models. But, for about the last 20 years of my career really focused on translational aspects of biomedical science, you know, trying to take something from the bench to the bedside, new drugs, new diagnostics, etc., etc. and there's a lot of kind of numbers, challenges in their data that needs to be analyzed appropriately, you know, drawing appropriate inferences. That's what actually led me to TJ and city of Hope. When the alliance was made, I thought, wow, this is a kind of basic biomedical science, nonprofit research institute connecting with the large health system. So we'll have the patients and the patient data, plus, some people on the inside who know the basic science.

Karie Dozer [00:02:26] What brought you to aging?

Dr. Nik Schork  [00:02:27] Yeah. So again, I'm interested in kind of quantitative aspects of science. So I really don't focus on any one disease area. So I didn't start my career as a diabetes allergist or a rheumatologist or an oncologist. I was analyzing data from different sources. I got very interested in the different areas of biomedical science, and then started to ask questions about what might unify those efforts. So are there factors that influence diabetes susceptibility that also influence cancer susceptibility, that also influence, you know, whatever else? And those more integrative biomedical science questions really motivated my research as of as of late.

Karie Dozer [00:03:10] What's your day-to-day work? What's the focus of your day-to-day research. Consistent.

Dr. Nik Schork  [00:03:14] So in that context I'm really interested in aging and longevity. Because the factors that contribute to aging are varied. And those are the very factors that contribute to susceptibility to disease. So I mentioned I'm interested in integrating things together. So and pulling things together. So aging provides kind of a platform for that because you know, as we age we become susceptible to many different diseases.

Karie Dozer [00:03:41] Everything.

Dr. Nik Schork  [00:03:42] It's everything that's right. Everything. And so understanding how the aging process impacts disease susceptibility of all sorts really is a question that requires the sorts of integration that, you know, I had mentioned I'm interested in. So it's a logical place for me to kind of land.

Karie Dozer [00:03:59] What's the headline if there is one to your area of research, what should we be excited about? Those of us who are aging and not able to do anything about it, right.

Dr. Nik Schork  [00:04:08] Well, there might be something we could do about it if the research amounts to anything. But yeah, what the most exciting, I think features of longevity in aging science, are, are one this kind of unity where there, there needs to be greater integration. So instead of having these research silos, the cancer people study the cancers in the diabetes people study diabetes. Instead, there might be these common elements. I find that fascinating and pretty interesting. But, also to your point, another thing that kind of motivates me and others in the field is maybe we could come up with interventions that actually could impact the way people age and thereby hopefully positively impact their susceptibility, reduce their susceptibility to age related diseases. So instead of making a diabetes drug and a cancer drug and a rheumatoid arthritis drug, we make an anti-aging drug that reduces our suspicion. Debility to all those diseases. So that's what draws a lot of people to this field.

Karie Dozer [00:05:11] I think everyone would buy that. Is that a focus of work worldwide? Is that sort of what everyone in your field is after?

Dr. Nik Schork  [00:05:18] Absolutely. So there's no question the race is on to try to see if one can come up with interventions that prevent diseases of all sorts, or able to treat multiple diseases. Should people have diseases, age related diseases? And there is a global effort kind of race to identify such drugs. And there's some candidate drugs out there rapamycin, metformin a carbo spent a decade okay. Acid which I'm developing a number of other candidate drugs. But there are issues and I'm sure we'll talk about these in vetting those and getting them, say, approved for use as general protectors.

Karie Dozer [00:05:55] What makes the search for a zero protector or something like this, this concept, what makes it so difficult?

Dr. Nik Schork  [00:06:00] Well, general protectors by definition, are drugs that impact multiple diseases. So that means you'd really need to understand processes that are more fundamental than any one disease process that might impact different disease processes. And there are examples of that. So metabolism is a process. If it's disrupted you get metabolic disease. mitochondrial function is another one. It's fundamental to a whole lot of diseases. DNA repair is fundamental process involved in staving off or if, perturbed, causing cancer. So there's three processes and there's many more that might be, appropriate to study if your interest is in understanding what's involved in multiple diseases simultaneously. So if we could develop drugs that target these more fundamental processes, then these drugs or protective drugs could. Fundamentally, beneficially affect multiple disease processes and thereby reduce risk for these diseases as someone ages. So yep. Global race. Pulling things together, not trivial. The different fundamental processes that might be behind all diseases instead of one individual disease. Hard to tease out. Hard to verify. So the race is on to find these.

Karie Dozer [00:07:24] You talk about a race and I know you're talking metaphorically about. We all want to find it as quickly as we can, but there is actually a race. Tell me what it is. And what's the prize?

Dr. Nik Schork  [00:07:33] Yeah, X prize. Yeah. So? So the X Prize is an organization that puts on competitions to kind of solve some of the largest problems facing society today. So they have competitions to, identify better biofuels. They have competitions to develop better diagnostic methods that could be used in the field. So in, rural Africa, you know, in the field, what could we do to diagnose disease? You can't go to a clinic and whatnot. So they have competitions to kind of motivate people to develop new technologies, breakthrough technologies to help this. Well, the X Prize health competition is about having people compete to see who can win the competition, to develop a general protector. So it's, 101 million plus dollars, devoted to the competition. If someone can come up with an intervention, a pill, a behavior modification strategy, whatever it is that ultimately slows people aging rate and returns them to about 20 years previous in terms of life, they'll win $80 million. And so it's just a way of motivating science. Lot of competitors out there. You know, I'm involved in, helping design the study. Like what criteria would people need to pass in order to win the competition? So I'm helping design the study.

Karie Dozer [00:09:01] You're helping to define this thing that everyone's trying to find, while you're also trying to find it yourself. Are you entering or are you judging? Yeah.

Dr. Nik Schork  [00:09:08] So this is a this is interesting where we have, this, compound called Pentadecylic acid or C15. It's an essential nutrient. It's been shown to have beneficial effects on all sorts of systems. So yes, we are thinking of entering this into the X Prize. Of course, if I do that, I'd have to recuse myself from any kind of judgments.

Karie Dozer [00:09:30] It would hardly be fair, but it sure would be handy. Yeah. From your discussion of. Of what? This this might be, it isn't a typical pharmaceutical or it might not be. It might be an essential element. It might be something that should be in our diet that we don't get enough of. Could the answer be that simple?

Dr. Nik Schork  [00:09:47] Yeah. Well, we know this is the case for certain, like nutrient deficiencies, so many people on a global scale suffer from certain nutrient deficiencies. And the way to correct those is to give them the right nutrient. But for people that are, you know, not malnourished, who also want to get an extra ten, 20, 50 years of life and be healthy, what could you give them? Because if it's known they're not suffering from something obvious like a nutritional deficiency, what could you give them? And this is an open question. However, just to put that into context, let's say we do come up with something that could add 20 years to someone's life. Would it work in someone who's malnourished? Probably not. So what you'd need to do is not only give them the pill to give them the extra 20 years but correct their malnourished condition. There's no doubt that maybe what people need to live a long time is sort of a cocktail. It might be nutrition plus pill, plus lifestyle changes. One of the interesting things about this, and I'm sure we're going to get to this later, is what might be needed, might vary from person to person.

Karie Dozer [00:10:55] So almost guaranteed isn't guaranteed.

Dr. Nik Schork  [00:10:57] Yep. You hit the nail on the head. So this is going to make the search for general protectors, probably one that will require people to come up with more individualized or personalized interventions. It might involve a new drug that could be given to someone in addition to other things they would need. But that combination of things that someone might need might have to be very individualized or personalized.

Karie Dozer [00:11:21] You've written about something called an end of one trial. Can you explain to those non-scientists listening, which are most of us, what that means?

Dr. Nik Schork  [00:11:29] Sure. And this bears on kind of this individualization or personalization of treatments. So an of one trials are just focus on an individual and whether they respond to something. So mathematicians use the N to define the sample size of a study. So a sample size of one means you're just studying one thing. So n of one studying one thing in this context, that one thing as an individual human. Being. So if I wanted to know if some particular intervention was benefiting you. What I could do is design a study, collecting appropriate data on you to make the claim that the intervention was benefiting you. If I did that, collected the appropriate amount of data, drew statistically and mathematically valid conclusions, that would be an end of one trial. So I am a big advocate of bit of one trial. What might work for someone, at least in the general protector space or any kind of disease context, might have to be personalized given differences between different people.

Karie Dozer [00:12:33] It sounds like a typical interaction between a patient and their clinician, their physician, that they might see for a specific problem. Often the course of action is to try one thing, and if it doesn't work, to try another. How is a trial and end of one trial different from that treatment of a patient?

Dr. Nik Schork  [00:12:49] Great question, because as you said, most clinical practice is kind of trial and error without a whole lot of objective data collected outside of whatever it is that the physician discusses with the patient. So if you come in and you're exhibiting signs of high blood pressure, your physician might reach into the medicine cabinet and give you one among many different pills that are to lower blood pressure and then send you home and then say, hey, look, if you notice any side effects, if you know you're having issues, let us know. If not, we'll have you come back in X number of months and see how your blood pressure is by measuring it. That's a long, slow, tedious and inefficient process. So with end of one trials, what we would do is we would want to collect, say, your blood pressure after you leave the clinic. Let's say do that every day so we can record what the drug is actually doing to you and know more objectively in a much-reduced time whether the drug is actually benefiting you. So the end of one trials are distinct from the standard clinical practice, in that more objective data are collected to make more efficient and appropriate inferences about whether something is working for you or not.

Karie Dozer [00:14:02] Obviously, it's more personalized, and it sounds ideal. Is it realistic, given that most doctors see hundreds of patients at a time? These trials, while we would like to do them for every condition, for every person. Is it possible to get there? Will we get there?

Dr. Nik Schork  [00:14:17] Logistically, this is a challenge. There is absolutely no question that that's the case. So maybe you could do trials on a subset of patients to learn whether they're allowing us to reach conclusions that might benefit others as well. So instead of trying to find resources to do this on absolutely every patient, there might be subsets. However, there are some developments in biomedical sciences that could enable these sorts of end of one trials. So for example, I'm wearing one of these Apple Watches that collects data 24 over seven. It collects heart rate and collects other things that might be relevant to your condition. So that's collecting kind of information passively. I don't even know what's on half the time. Maybe that information could be used by a physician to determine if you're, say, heart rate's lowering medicine or your blood pressure lowering medicine is actually working. And in that way, you could deploy this at a much larger scale. But we're not quite there yet. With all the devices or all the assays, we'd need to really make these objective claims in an efficient. And in a way that's transparent to the patient.

Karie Dozer [00:15:21] And where do we keep all the data?

Dr. Nik Schork  [00:15:23] That's a great question. Fortunately there are some developments, as you know, in in computer science and in artificial intelligence and machine learning that give me reason to believe and other people reason to believe that despite the massive amounts of data, we might be able to efficiently analyze them, draw appropriate inferences. And you see this too, with developments in AI. You see things like large language models in the form of ChatGPT that can take massive amounts of information and distill it into a single sentence. Hey, this is working for you. That's the vision. Whether we're going to get there in two years or 20 years is an open question, but there's reason to be optimistic.

Karie Dozer [00:16:06] You're also involved with something called the Longevity Consortium. What is it? Yep.

Dr. Nik Schork  [00:16:10] So as I mentioned before, I'm very interested in kind of pulling things together to see if the results of studies in one particular setting really do complement studies in another. And I'll be more specific in studying aging and longevity. You can study it in the petri dish. You can go into a lab, do all sorts of things to bio specimens from patients, all in the lab. You could also study aging and say non-human species like mice. This is done all the time, might turn humans, but they could give us insight. You could also go out and collect data on massive populations, say, of older and younger individuals, and look for the differences. Well, right then and there, there's three different approaches that you might take to try to unlock the secrets of aging. What I would argue is you'd want to. Pull them all together. Do the insights from the lab experiments. Really say the same thing as the experiments on the mice. And do they say really the same thing in humans? If the answer is yes, whatever it is that was revealed in those three sorts of studies, it's going to be highly compelling. So the Longevity Consortium is made up of a group of investigators who at some level, have agreed to trade notes and figure out how they can work together and use the complementary approaches they're taking to, in fact, come up with more compelling claims about what is involved in aging and longevity.

Karie Dozer [00:17:29] All of you different groups are in different physical locations. You use different methodologies. How do you communicate? What are the barriers.

Dr. Nik Schork  [00:17:36] Barriers of, you know, there are physical barriers. Fortunately, zoom we live through Covid. So a lot of people came out of that thinking, hey, it's not so bad to get on a call every now and then instead of flying across the country. Bat. So a lot of virtual interactions, a lot of emails. You know, face to face as well. A lot of results sharing too. So if somebody says, hey, I found process X was involved in aging, you send it over to someone else's lab who's taking a slightly different approach. So a lot of exchange of information beyond kind of physical interaction, say, in a conference room.

Karie Dozer [00:18:10] How long has this longevity consortium been around and how long will it last? Will it live beyond the researchers who are working in it now?

Dr. Nik Schork  [00:18:17] Great question. So the Longevity Consortium was started about 18 years ago and is likely to continue on in the future because of the emphasis on this unification of ideas, of strategies to get at what is and isn't causing disease, where aging might be a key. So we all know that the aging process contributes to susceptibility to disease, right? So if we could understand the fundamental mechanisms aging, maybe that would shed light on, again how we could come up with a general protector and reduce susceptibility to all these age-related diseases or treat multiple age-related diseases simultaneously. Since that problem is here and plaguing us, I can tell you the Longevity Consortium, or at least efforts like the Longevity Consortium are going to exist.

Karie Dozer [00:19:08] It's the one constant. It's the one thing that nobody can prevent. Is it the number one factor, or are there other things that are more important when it comes to whether or not we get sick?

Dr. Nik Schork  [00:19:18] Yeah. Great question. So of course there are other factors that contribute to disease environmental exposures. So you could be exposed to toxic radiation at 12 years old that can lead to disease is not much to do with aging. So there's unquestionably, a number of factors that are more environmental in nature that probably are contributing to disease over and above the aging process. However, the aging process is fundamental to many age-related diseases cancer, diabetes, heart disease, and probably exacerbates the kind of, adverse effects of exposure to environment. So gene environment interactions, as they're called, you know, aging by environment interactions, these things exist. So, yes, the answer to your question is there are things beyond aging that contribute to disease, but aging is one among the things that contribute to disease.

Karie Dozer [00:20:10] What have I missed in asking you about your work today or in the future?

Dr. Nik Schork  [00:20:15] Well, one thing that's very interesting, and we were talking about Gero protectors and how much interest there is, you know, many billions of dollars being spent. There's a lot of investment in the space. You may have heard, Jeff Bezos and some of his colleagues put $3 billion into Altos Labs, creating a Nobel caliber, group of researchers to really try to understand what it is that we could do to affect the aging process and benefit people's health. So a lot of money, a lot of time and energy being expended for all the reasons you discussed. However, one issue that's important to consider is how regulatory agencies are going to deal with the onslaught of insights into drugs that might actually affect people's health overall. Because right now, the way, drugs are vetted is they're associated with what's called a primary endpoint. So diabetes drugs get approved for use in diabetes and heart disease. Drugs get approved for use in heart disease. And that connection between each pill or each intervention and a primary outcome.

Karie Dozer [00:21:23] Is direct, is.

Dr. Nik Schork  [00:21:24] Very specific. And that has been the legacy way drugs have been vetted. You must test them for use in the conditions that you're making the claims for. Now, for all the reasons we talked about geroprotector, drugs are supposed to impact multiple systems and thereby not be confined to only affecting rheumatoid arthritis or diabetes. So a question is, how are we going to prove that they're actually doing that when all the infrastructure we have is focused on testing drugs and specific primary endpoints? So that's. Something that's emerging. That's something that society and governments are going to have to deal with. But it's coming.

Karie Dozer [00:22:03] Are you involved in the process to change the way these substances might be regulated?

Dr. Nik Schork  [00:22:09] Absolutely. And so, as you know, there are regulatory agencies within the United States, the FDA being the biggest one. So I have had recurring calls with the FDA about end of one trials, about gel protectors, about integrated biological research. I've given talks at the FDA to make them aware of what's going on, and they've been receptive. So whereas I can't guarantee that anything I've said to them is going to result in legislation tomorrow, that might result in a sea change, and now there'll be a flood of gel protectors on the market. They're sympathetic to listening to this, I think, in part because they know this is a reality. Yeah, that you're going to have to deal with someone listening.

Karie Dozer [00:22:50] Might want to know what it is that you do, how it is that you live your life. You know everything that there is to know about aging well, or at least as well as we can. Any little bits of advice as we say goodbye? Sure.

Dr. Nik Schork  [00:23:02] Well, you know, I do things that I think are very logical. You know, I exercise, I eat, right, I do go to my annual physical, you know, routinely I pay attention to developments in this space. All that is crucial, you know, in terms of things that I take, I do take Pentadecylic acid or C15. You know, the one potential protector that I had mentioned before. That's the only supplement I take right now. But, you know, also other things that I'm, acutely aware of that I think others should be aware of that could compromise one's health. Stress. You know, we live in very kind of complicated times. I mean, can't turn on the TV without stress a little bit. All of us have to learn how to deal with that. So I think the more logical things that have been encouraged for decades, everyone should adhere to. But I would pay attention to the development of these general protectors. Keep your eye on it, because there is likely something that's going to occur within our lifetimes that could have health benefits that, you know, would have broad effect.

Karie Dozer [00:24:07] I look forward to it. Hopefully you'll have some good news for us. Thanks so much for taking the time.

Dr. Nik Schork  [00:24:11] Thanks for having me.

Karie Dozer [00:24:13] For more on TGen’s research, go to tgen dot org slash news. The Translational Genomics Research Institute, part of city of Hope, is an Arizona based nonprofit medical research institution dedicated to conducting groundbreaking research with life changing results. You can find more of these podcasts at tgen dot or slash TGen Talks, Apple and Spotify and most podcast platforms. For TGen Talks, I’m Karie Dozer.