The TAME trial and beyond (Dr. Nir Barzilai — AECOM)

Welcome to Translating Aging, a podcast about how the science of human longevity is transforming the way we treat disease. In each episode, we bring you conversations with the researchers, entrepreneurs and investors who are working at the vanguard of the field. Translating Aging is produced by BioAge Labs, a clinical stage biotechnology company developing therapies to extend healthy lifespan by targeting the molecular causes of aging. I'm Chris Patil, VP of Media Media at BioAge. Joining us today is one of the titans of geoscience, Professor Nir Barzalain, founding director of the Institute for Aging Research, the Nathan Schoch center of Excellence in the Basic Biology of Aging, and the Paul F. Glenn center for the Biology of Human Aging Research at Albert Einstein College of Medicine of Yeshiva University. He is also the author of the recent book Age, healthspan, Lifespan and the New Science of Longevity, which I personally recommend to anyone who hasn't yet picked it up. In parallel to his own groundbreaking work on the genetics of aging, Nir has worked tirelessly to bring aging research into the mainstream and is now working on multiple fronts to make safe and effective aging therapeutics widely accessible. I've been attending Nir's talks for more than 20 years, even since before I entered the aging field, and I'm thrilled that I and the listeners of Translating Aging have him all to ourselves today. Professor Barzilai, thank you so much for joining us.

Thank you. My name is Nir. Thank you for this introduction that only says how old I am. Really.

All right, if it's all right with you then, Nir, I'll call you that for the rest of the call. Happy New Year. By the way, how's 2022 treating you so far?

Happy New Year so far. It's been great.

Glad to hear it. All right, I just want to dive right in. I have so many questions for you. In order to treat aging, we need to overcome many kinds of obstacles, both scientific and regulatory, and they're each rate limiting in different ways. We know that you can speak fluently about the scientific aspects, but in this interview, I mostly want to focus on on the regulatory matters, the legal, societal and governmental structures within which longevity biotech is operating. So first, can you tell our listeners about the ways that you think existing regulatory frameworks create impediments to longevity biotech as a sector?

Yes, sure. Then that's a great question. And in fact, look, yeah, I'm a scientist, but my really major mission these days is to lead this trial that's called tame so that there's a pathway for drugs that target aging. Let's call them gerotherapeutics to go into mainstream. So there are several obstacles, and I'll start with the first one, the fda. But it's not only fda, it's the government. And other scientists don't really know the major news that aging has a biology. I mean, we all know that aging has a biology because we know who's old and who's young, but that this biology can be targeted and aging can actually be delayed. Aging drives diseases, and those diseases can be delayed. And that we have shown that we can target aging and we can enhance healthspan and lifespan. Okay? This thing that is so trivial, everybody in our field will say the same sentences is not something that's uniquely accepted. So, for example, you can get an indication for a drug that treats sarcopenia and frailty. And I will tell you, this is a setup for failure. Those are end diseases, okay? It's very hard to take a sarcopenic muscle and rejuvenate it on an old body. I think it's more important to say, why don't we just prevent sarcopenia? Why don't we just prevail frailty? Because this is easier to do than take a pretty much dead organ and try to rejuvenate it. So this concept that aging can be preventable and prevent a disease is a major problem. This is as far as regulation, but it goes beyond regulation. When the FDA was established in 1938, there was a list of diseases that the FDA was in charge of trying to cure. Most of them are irrelevant now. Like, tuberculosis is a treatable disease now. And the question was, do we need to identify aging as one in a disease to make progress? And, you know, a lot of us say yes. And I say yes to the idea that if aging drives all the diseases, then it's the mother of the diseases. Okay? Of course it could be identified this way, but practically, this is a big mistake, because look, after the COVID experience, elderly don't want to be called old because what happened, you drove them into isolation and loneliness. I mean, is that what we're going to do? We're going to declare everybody above 65 that they are sick? And what about those who are not sick? What about those who are biologically young? Are we going to call a whole population? They don't want it. And those are the people we want to help. They don't want to be called sick. The FDA doesn't want to call them sick. The aarp, the retirement organization, doesn't want to kill the elderly. Sick American Federation of Aging Research doesn't want it. Call them sick. And we found out in negotiations with the FDA that we don't need to call them sick because after all, what are we trying to do? We are trying to prevent a cluster of age related diseases. We know it's aging, we call it aging. And they don't have to, but we have a template to move on.

And actually this is a great segue into the very next question I was going to ask you, which is I want to talk about this clever way that you've devised to advance the clinical application of aging biology while avoiding some of these pitfalls that you just mentioned and overcoming some of the regulatory obstacles that were sort of implicit in my first question. Of course, that's the TAME trial, which you already mentioned, and that stands for targeting aging with Metformin. For our listeners who've never heard of it or maybe aren't familiar, what is metformin?

Metformin is a drug that it's actually a nutraceutical, you know, it's an extract from the French Lilac.

I didn't know that. I never knew it was a natural product.

But it was modified. Okay. And it's a drug and you need a prescription. So it depends if you want to feel good about it or not, but it's really an extract of the French Lilac that is manufactured. It was used hundred years ago to treat flu and malaria and inflammatory diseases. When it popped parallel. It was also discovered that it lowers glucose in diabetic patients. And really it was hijacked to diabetes. The good news is that it's used for diabetes for over 80 years. Since diabetes is a chronic disease, there are tens of billions of people's years experiencing metformin. I don't think there's any drug that has been used more. And because of that, we know a lot about this drug. There are really two things that we need to know as major about this drug. A, when you give it to animals, they live healthier and longer. And B, when you give it to people in clinical studies on, when you look in association studies, it has been decreasing all age related diseases, cardiovascular, cognitive and Alzheimer's cancers, and it's even decreased mortality.

And to be clear, this is in retrospective studies for people who've gone and they've taken cohorts of people who've been on the drug and they've said looking back over the last 20 years, these people have seem to have less of these diseases. Am I getting that right?

No, no, no. When I said clinical studies I meant control studies. So two examples. The diabetes prevention trial was giving metformin to people without diabetes and seeing if it prevents diabetes. It had a 30% effect. The study had to be ended early in order to allow the placebo to go on metformin. Another study is the UK pds, where the UK PDS is a big UK study that was comparing the effects on metformin versus insulin or sulfonylureas, which is other drugs to treat diabetes. Again, a clinical study. And metformin had benefits on cardiovascular outcomes. There are clinical studies on people with mci, that's mild cognitive impairment, that without diabetes, people without diabetes, they got metformin for in one study for six months, in another study for a year. And they showed improvement in some cognitive domains. So there are clinical studies and they are association studies. I think the very convincing association studies are on cancer. There are about 250 papers now about patients on metformin and all of them are showing the same thing, that people on metformin have less. 30% less of any cancer. Maybe prostate cancer is not definitively, but almost all other cancers are less with people who take metformin. So I'm just protecting. It's not that it's noticed by association studies that are known to be complicated and not always predictive. Those are clinical studies. In fact, I would say that every part of the study that we do in TAME has been done for a single disease, but we're doing for all of them together.

This is a great time to talk about what the actual trial protocol is. How will you be targeting aging with metformin and what will you be reading out?

So we are going to take about 3,000 people. We might extend it to 3,500 post Covid calculations, but 3,000 to 3,500 people in 14 to 16 centers in the United States. And 3,000 people will be divided to placebo and metformin and be followed up for up to six years. We ask for funding for six years. It might happen earlier. I hope it does. And the primary outcome that the FDA wants to see is that we move a cluster of disease. In other words, if the cluster of disease will happen in control, it will be prevented or delayed in people on metformin. So it's the time until events. The really cool thing about this study, which is really different than any other study, is that since we are coming from an aging perspective, since aging is driving this disease, we don't know which disease you're going to get next. If your mother is diabetic, and you're obese, you'll get diabetes next. But we are agnostic. Every disease that you're going to get, you're going to get the point. And it's really the cluster that is our outcome.

Could you quickly just run down what diseases are in the cluster?

Yes. It's cardiovascular disease, cancer, cognitive decline and Alzheimer's and mortality.

And you're going to be studying, you said up to 3,000 to 3,500 potentially people. And these will be people who are already elderly between the ages of 65 and above.

Correct. Those are people that they are not totally healthy. They have to show signs of aging. Right. We don't want to recruit 3,000 people who will be centenarians. We'll never get anything from them. So they have to have something. They have to be slow walker or had already an age related diseases so that we can predict that they are at high rate of getting a second disease or some outcome in the next couple of years.

I see. And is the idea that they have to have some sign of aging was that important to getting the study approved? Like, is it easier to get the study approved if you're targeting people who already have an illness and you can't just start with completely healthy people?

No, the calculation to do that is because if you start the study at age 50, for age 50, you don't have enough of those outcomes. So we needed a bunch of people that have a lot of outcomes. We know also from other studies that it's never too late to start a general therapeutic. The mechanism of aging exists even after you got your first disease. So we chose the age where there's enough event for those 3,000 people to get an outcome.

So let me make sure I understand the logic of the trial. Aging is the primary risk factor for multiple diseases. And these diseases are, at least on the surface, quite mechanistically different. So if we find that this drug can delay the onset of more than one such disease, it must be affecting the underlying aging process that puts us at risk of illness. Do I have that right?

Yeah, you just passed the test, the final test in flying color. That was really nice.

Excellent.

Send me the text so I use that the next time.

I'll send you a transcript. Thanks very much. I'm glad that I got it right. It's a great idea and it kind of cleverly circumvents a lot of the obstacles and objections to, as you said earlier, defining aging as a disease, which is problematic from a societal standpoint as well as kind of from a medical standpoint here, you're simply saying we are seeking to delay the onset of a cluster of age related diseases. And you and I both know that that means that we therefore must be targeting some underlying unifying aging process. That's fantastic. So beyond the primary endpoint, what other kinds of data will you be collecting over the course of tame and how will these be used?

The most important thing after proving the FDA is to really get a good set of biomarkers that will be available to the growing industry. So look, we have developed biomarkers for aging. It's been accelerated in the age of omics. I'm dealing a lot with proteomics. Bioage is dealing with proteomics too. We're dealing with methylations, we're dealing with metabolomics. We're starting to close on really a lot of biomarkers that are associated not with chronological age, but with biological age. But the most important thing is to find those biomarkers that not only tell me what's the biological age, but if I intervene, will they change? Also will they predict the effectiveness of any of those drugs? So this is a major thing that we're going to capture in tame. In other words, we're going to have enough resources, enough blood and plasma and DNA to establish a whole set of omics in order to capture what have changed in the first few months of treatment in tame and how would that predict the outcomes? And I think this is really important because you cannot do what we're doing. It's a phase three trial, basically, you cannot do it for any drug because it's a, you know, kind of a billion dollar investment. And we know that 95% of those studies fail. So we need to have some biomarker that we can do a phase two study over a couple of months and show that indeed it changes biomarkers for aging and therefore it makes sense to go and try the drug in a phase three trial.

What is the planned use and distribution of these biomarker data that you collect? Is the idea that they're going to become available for licensing by pharmaceutical companies? Are they going to become publicly available in some sense? Like how will they be useful to academic research as well as to industry research?

Well, no, they're not going to be commercialized. They're going to be available. First of all, they'll have to be a consensus and scientists will have to look at them very well, will probably have arguments of stuff, but they're going to be posted as soon as we can. They cannot be patented because natural Things cannot be patented. You know, I've been finding longevity genes. I used to patent them initially, but you cannot patent anything anymore like that. That doesn't mean, by the way, that there's no marketing opportunity. Right. That companies will take sets of biomarkers and make them available for people to test. But that's not keeping it from the science or the companies or anyone who wants to use those biomarkers for whatever they need.

That's fantastic. So one of the things that's going to come out of tame, in addition to the primary endpoint and our knowledge about whether metformin is capable of delaying the onset of diseases of aging, is a giant resource of biomarkers and other information that can be used by the longevity biotech sector going forward in order to test drugs more rapidly and monitor our progress in a quantitative and objective way that we really can't right now. It's one of the greatest challenges of the field.

Better said than what I've tried to do.

You're much too kind, Nir.

Thanks.

You've set us up very well to understand the purpose of the trial and how it's going to be run. We have a sense of the ambition of it. Obviously, things like this aren't cheap. What is the status of the trial?

Right now the trial is going to be run by the American Federation of Aging Research. That's going to be the supervising and funding source. The money itself comes from a source that I cannot reveal now for lots of reasons. And the trial will start first of all, when Covid is over. Which one of the. You know, this study was delayed several times. We lost funders for a variety of reasons. And then Covid started and we were lucky in a way. Well, we might have been lucky. You know, around the world, there are nine studies that showed that people on Metformin had less hospitalization and less mortality from COVID if they were on metformin.

I mean, that's not surprising, actually, if we believe that metformin is a broad spectrum. I know you don't like the word anti aging, but a broad spectrum JIRA protector.

Right.

You would expect it to have positive outcomes on the aging immune system, which, as we know, the deterioration of immunity over the course of aging makes elderly people particularly susceptible to Covid, to the point that many people have called it a disease of aging. So it's not surprising to me those studies gave those results. It's also not surprising to me that Covid caused problems with your study. As an employee of a company that's running clinical Trials right now, during the era of COVID it has really gummed up the works around the world. So I can totally see the advantage of waiting a little while. But I want to go back to something that you said. You're playing your funder close to the vest, but it sounded like you implied that the funding is set and ready to go for whenever the study is ready to start. Am I hearing that correctly? Yeah.

And as you said it so carefully, I'll add that the money is not in the bank yet, but we're comfortable that it's in transit, so. But it's not in the bank.

Okay, so I see. So the order of events then is by some definition the pandemic will end. The definition of the end of the pandemic is a bit slippery as it transitions into something resembling more like endemic seasonal flu. But at some point we'll say, okay, the pandemic is over enough that we can go ahead with this trial. And then the next step will be this big check will clear and you'll say the money is now in the Bank. And then Afar and 14 Centers who are going to be running the trial will start recruiting patients. Is that the order of events? Yes. How long after the trial starts? And let's say the start day is the day the first patient is enrolled. How long after that do you hope to see interim results?

You know, it's hard, Yogi Berra. Right. It's hard to make predictions in particular about the future. And I'm known as optimist. And so I'm thinking, boy, we could do it in a little bit over four years. But the truth is we don't know. I'm pretty confident that six years are enough, but I really hoping that it'll be before.

Okay, so you have a six year kind of plan for the study. You're hoping that the data are strong, the effect size is large enough that you can start making calls earlier than that. But obviously the reason why we have to do studies is we don't know what the results are going to be yet. Right, Right. So, okay, I understand that you're an optimist and I appreciate you making that qualification. So you're. Now everyone knows that NIRA is optimistic. Let's imagine ourselves now a few years in the future at that four or six year time point when the results are in. And let's further imagine that the results are positive. What happens next?

I think what will happen next? And by the way, I should tell you, it's happening now. A large percentage. What Is large percentage. More than 1% of the population, probably of the elderly population, is probably already taking Metformin. The sales of Metformin around the world has increased by 50% in the last years. And it's not because diabetes Is increased by 50%. So a lot of people are trying that. I know just me and my colleagues know it just because of the number of emails that we're getting either to prescribe Metformin or the cuter one are we would like to volunteer for this study. As long as we're not on the placebo.

Right.

People are interested. And I think what will happen next is that health care providers will be eager to implement that. And why? Because Metformin is so cheap. You know, the problem with health care providers is new drugs that are costing a lot of money. And that's not going to happen with Metformin. I mean, even if Metformin doubles the price because of demand, it's still going to be the cheapest drug in the pharmacy.

Can you put some numbers to that? Like when you say cheap, do you mean like it costs $5 a day? It costs, like, how much does it cost?

Well, 500 pills are for $50, approximately.

Oh, wow.

It depends on the supplier. You know, many people are getting their metformina from Mexico or glucophage from Canada and it's much cheaper.

I see. But we're literally talking about Chinese appeal. Much less than a dollar.

Right. We're talking dependence. And if you're interested, let's talk about the economy of that. Okay?

Absolutely. I absolutely want to talk about the economy of that.

So let's start with this fact. There's a study out this year by professor of Economy in London School of Economy. His name is Andrew Scott. I can forward the paper to you.

I have it on my desk right now. And I've been in correspondence with Andrew. Yes, absolutely. Go ahead.

Let me tell you, it's very difficult to understand. I spent time with Andrew. I tried to talk with the reviewers of the paper that couldn't explain to me what's in the paper. Andrew Scott explained it to me, and I'll tell it very simply. We were always looking at the medical expenses in the last two years of life and for example, in centenarians. And I'm studying centenarians. It's third the cost compared to what you spend on 70 years old. This is CDC data. So there's a lot of saving by being healthy. Healthy and dying with a contraction of morbidity, you know, not being sick at the End of life. So Andrew Scott basically said, hey, you're really underestimating it. Why? He said, because, you know, if you're going to contribute a year or two of healthspan, then there are other things that happen. It's not only that they're not sick, but they're going to travel, they're going to buy gadgets, they're going to buy, I don't know, house for their kids. The value, the economical value of those people is immense. And 40% of the resources in the world, of the money in the world is owned by elderly people. So he said, you underestimated. And it really, it's trillions, 300 trillions of dollars in the next 10 years. Now he's doing another very cute thing, and that's why I mentioned it. He took all the data from our study for our grant, really, and he calculated, and he shows that people who will be on Metformin in my study, they're going to benefit from not having cancer, not having diabetes, not having cognitive function, or less of them, of course. So you add those up, and then you also add up the additional value because those guys are going to be out there spending money. And so he calculates that for the 1500 people, basically, that are taking Metformin, we are going to save $150 million of value. This study is going to cost us $50 million. So we are actually contributing $100 million to the economy by doing this study of, Wow. I think when healthcare providers will see that, they'll say, sure, sure, get on Metformin and we'll start cutting costs and making more money, Right? Cutting cost on health and making more money. This is one way to look at it. Now there is another way to look at it. And let me make a provocation here, because it's not only about people who are 65 years and older. It's about people who survive cancer. And they're aging rapidly because we just give them radiation, right? And chemotherapy that ages them. Children with cancer get heart attacks, sometimes at age 35. They're rapidly aging. People with HIV get diseases 10 years before their age. Disabled people. But poor people, too, because poor people, they're interacting less with two major things. Their nutrition is bad. Not that they don't have food. They don't have the right kind of food. Right. They don't eat fish, they don't eat fruits and vegetables. And also they don't exercise because they cannot afford the gym, or maybe gym is not in their neighborhood. And they cannot afford buying whatever machines. So if you think of it, if you want to spend money in order to buy better food and provide it to to the poor people and by the way, also convince them that this food that they don't like is something that they should eat anyhow, okay, you're going to spend a lot of money. If you want to build gyms and make them exercise, you're going to spend a lot of money. But if you give them Metformin, you're going to spend hundred thousand dollars for every $1 of metformin to make it equal with the other interventions. Now, please understand it's a provocation. I don't really want anybody to say we should find a way to pass nutrition and exercise. I'm talking from a value perspective, right?

It's a thought experiment that illustrates the point. I think that you are describing a world in which the TAME trial's positive results, if positive they are really lead to a transformation in the way we think about diseases of aging. We adopt a more preventative approach and we recruit providers simply because the value proposition is so obvious. Healthcare providers are going to get on board and start encouraging patients to get on this medication and hopefully reap not only economic but also health benefits for lots and lots of people. And that sounds fantastic. So a related question is, do you think that in a world where TAME has yielded positive results, that this leads to a series of other similar trials of other drugs with similar endpoints to tame?

Yes. Part of the idea of TAME is to have a template so that any company that has a medication, they can use exactly our template and make basically the same investment in phase three trial. I would tell you that because we use only 3,000 people or 3,500 people for any single disease, you would need to do study in more than 12,000 people with diabetes. You have to do enough trial to show that there is a cardiovascular outcome. So we are giving a template that is going to be much more affordable for people to do that. Another point I want to make, we are preparing exactly paper. We actually submit. There is a paper in review where we looked at all FDA approved drugs that have a geroscience sign of them. In other words, every drug that showed to extend lifespan in a mice or in an animal model. Actually no, in a mammalian, in mice or rats. And we think that there'll be several TAME like trials in parallel to this TAME trial. Because I think maybe pharmaceutical will be interested to increase their drug purposes and definitions. So maybe that will happen in parallel too.

So I want to shift gears a little bit it's clear from the conversation we've had thus far that tame is kind of a clever way to play within the existing regulatory framework, but ultimately result in an expansion of that framework. And what I want to talk about for the next little while is you're already very invested in other efforts to expand sort of the regulatory and legal framework for putting aging therapeutics into the clinic. You're one of the founders of the Longevity Biotech association, which is an alliance of founders and scientists and investors who are working to develop therapies that treat the root causes of aging. And in this vein, I should mention that the CEO of BioAge, Dr. Kristin Fortney, is also one of the founding members of the lba. The group has an ambitious mission, and two of the main aspects of that are to educate the government, media and public and to work with regulators. Those are obviously related to each other. The educational mission is important to the work with regulators. What I want to invite you to talk about now is how is the Longevity Biotech association going to achieve those goals? What happens first?

Actually, we launched this association just in November in London, and those Fortney and Kristin and some of the founder are going to have our initial work meeting next week. So I'm not going to say much more before we approve a plan, but this is the highlights. Okay, first of all, my mission there, I'm representing the American Federation of Aging Research as their scientific director. I'm also representing the Academy of healthspan and Lifespan because what we want to provide, because this gero biotech, longevity biotech is kind of new and we're trying to get more people in, we want to hook them with the right scientists so that they can tell them the story. And the reason that is very important is because we have those hallmarks of aging. Seven to nine hallmarks of aging. We all agree that there are several hallmarks of aging. We're still arguing if there are seven or nine or which, if there are hierarchy between them. But to be a hallmark of aging, you had to show that something goes wrong with aging and if you fix it, you get an extension of health span and lifespan. That's how you become a whole. It's not the same as the causes of aging, but it's a good way to start. And the way investors are dealing with this, they are pretty much choosing a hallmark. So investors will come and say, hey, what's your favorite hallmark? And I said, well, if I had eight daughters, I wouldn't tell you who's my favorite daughter. So tell me what you want to hear about. And I'll tell you what you need to know so we can assign expertise and educate the investors on the science and the hope and promise of a certain hallmark or a certain approach. So that's about how do we recruit intelligently more people. The second thing that we have to deal with is the fact that there are standards that we have to talk about. So for example, if you want to get all the way to longevity, it's a longer Runway, okay? Your company needs a longer Runway than to get just to a simple disease. So you have to think about the standards. You have to think about what it means to go to longevity, what resources you have, how do you talk with your investors in each company and what are other things that are industry specific. What is it that you really can say of something that is a gerotherapeutic? You know, maybe you are using the term, but it's not really a gerotherapeutic because we don't know, we don't have evidence that it enhance healthspan or lifespan of anything. So there's a lot of standardization that we have to do. The third thing is education. And one of the things we were considering to do and we decided not to, is to do lobbying. I'm actually involved in a lobbying effort here in the United States. But because the association is international and it has people from all over the world, from China, from Russia, it wasn't making sense for foreigners to be involved in lobbying in the United States. So we kind of spread it out to somewhere else, which is actually quite an interesting story. So those are examples of the things that are moving us now.

That's a really nice statement of mission. And I understand that you don't want to talk about what happens first before you have your meeting next week with the leadership of the organization. But can you just pick maybe one or two dream outcomes for the next five years? Like what's on your wish list, like your personal wish list in terms of outcomes and results?

Oh yeah, look, it's very simple. The total money in longevity biotech is estimated to be $12 billion. And by the way, I'm quoting somebody, I don't know how they accumulated the

data, but it sounds right to me.

But it doesn't matter. But it doesn't matter. So there was about a billion dollar investment about three years ago. There was a four and a half billion investment in the last year. And so we are looking for an exponential investment. We want the whole world to be investing in longevity rather than in other things. So the mission is to make it the next big thing. Okay, the next big thing in the industry, or to count the investment. And if you ask me how many, you know, $100 billion. Okay. I want it in the next five years to be $100 billion industry. That's really what we need to do.

You know, I think that sounds achievable, and I think that what's nice about it is you have, like, a specific number that's measurable. You'll know how well this is going, and you'll know that you're winning. When Longevity Biotech has its $100 billion, and the oncology field needs to have a bake sale to raise money for its next drug. I certainly wish you the best of luck with getting to that goal. Last month, in a related vein, I had the privilege of sitting on a call with you and several luminaries, including two former members of Congress, one of whom was speaker of the House, entitled Creating a Bipartisan Movement to Increase Healthy Lifespan in the United States. What I was struck by was how much these two politicians, neither of whom were scientists, how much these two politicians knew about the value of what you and I would call the geroscience hypothesis, the idea that because aging plays a major role in many diseases, therapeutically addressing aging will prevent the onset or mitigate the severity of multiple diseases. So was that knowledge, the politician's ability to talk about this so fluently, was that the product of past educational efforts on the part of you or others?

Oh, absolutely. Look, Newt Gingrich called me about a year ago, and he said, is that true? I mean, I hear that aging doesn't have to be that way, that we can prevent aging. Is that true? I said, yes. He said, well, tell me your story. So I wasn't the first one, and I wasn't the last one. Newt Gingrich. It clicks. Steve Israel sounds. It was the same for me. The eureka moment in this meeting was something that I asked because they said, it's a bipartisan issue. Okay, it could be a bipartisan issue. And I said, just a minute. Science is not a bipartisan issue the way I see it now. And Newt Gingrich kind of took over and said, no, no, no, you misunderstand. It's not the science. It's the fact that the government makes you take something. Some drug, right? Some vaccination. He said, but if we're going to hit aging, it's going to be bipartisan because you are not making people take it, right? If you want to, you take it. If you don't, you don't take it, which I hope that's true. They also said something interesting, that all member of Congress, whether they are far right or far left, need to show that they work across the aisle. And so they are looking for agreements like that so they don't have to fight about the politics of others. So I think, and look, those are really important people because they've been really top leadership in the Congress. So they kind of know the game and they seem to be very committed to the cause.

That was my impression as well. And what I wanted to ask you about is in your interactions with politicians and people in government who are policymakers, you talked about your one eureka moment about framing the issue in a way that was palatable to people on both sides of the aisle. But what other aspects of the conversation with government are challenging that are harder than you expected them to be and are obstacles that you feel like still need to be overcome?

So I was meeting about tame, and that was probably five years ago, Senator Cochran from Mississippi, who was actually the head of the Ways and Means Committee, so he's probably the most important senator from a financial right, from an influential point of view. So I learned some things and the first one was the preparation. The politicians have to sign few things and the first is, is it good for their states? So with Cochrane, I said, you know, you're in Mississippi. The rate of death from cardiovascular cancer, all those diseases is the highest in the country. Okay. The rate of obesity is the highest in the country. And there's less metformin usage in your state than any other state. And Senator Cochran said, what's the problem of my people? What is the problem of my people? I said, Senator Cochran, your people are victims. They're victims for the good food of Mississippi. They cannot help but eat a lot of the good meat of Mississippi. And he was so happy, he said, I'm going to use it. They are victims. They are victims of, of the good food. But the point is that when you're a lobbyist, I discovered when you're a lobbyist, you have to be really to prepare. You have to check what's good for your people, if it's good for your people or for your party, I guess then you move to the nation and the world. So one of the things we're trying to get a senator from Pennsylvania involved and we've identified a really good gero scientist in University of Pennsylvania. So we'll have to check can educate people to do the right pitch when we get to that.

Yeah, there's this old saying in the US that all politics is local. And what you're telling me is very consistent with that.

By the way, there's another lesson that I learned. So Senator Cochran, so what are they doing? He didn't come and say, you know what? I'm doing the budget. I'm just going to put $50 million from it for me. Right. He said, you should go to the Department of Defense. Department of Defense, everybody knows, has a lot of money. You can get extra things through there. We went to the Department of Defense, but there was another set of problems that we're not prepared to because they do have a list of diseases that they are ready to treat, but aging wasn't part of it. Right. So we try to be wise about it and say, you know, you have diabetes. Well, a drug that treats diabetes actually also prevents other diseases. It didn't go well because it wasn't diabetes.

Your LBA is an example of the field helping itself. All right, are there other things, Are there other initiatives that you can imagine that haven't gotten off the ground yet? That haven't gotten started? Are there things that the industry, that the sector, the field should be doing to help ourselves that we haven't yet started to do?

So I'm focusing mainly on getting enough money to enhance the pipeline. Look, as I said before, we have hallmarks for aging, but those hallmarks is not equivalent to the mechanism of aging. I'll give an example, you know, because people know about rapamycin, and rapamycin is an MTOR inhibitor, and MTOR increases with aging. So when you give a MTOR inhibitor, you get better healthspan and lifespan. But that doesn't explain why MTOR increases with aging. Okay, we're not there yet.

We.

We're trying to get more things, more upstream and downstream things. So we need much more science, and we have to get A, more money to the science of the biology of aging, and B, we need to get more people to do this science because most of the scientists are not geoscientists and we need to pick the people that actually have the capacity to enhance our field. We need more regeneration people. We need more stem cell people. We need more technology people. We need people who can do machine learning to solve some of our problems. So we need to extend the field and extend the actual funding to do it. And the reason I'm saying it is, look, I'm always talking about three things that is easy for the public to know. One is the Dorian Gray scenario. Right? Dorian Gray was not Aging. But when he looked at the mirror, he saw his true age. By the way, you should try it. It's working for me. I'm looking at myself in zoom and I say, oh, I'm much younger. That's a Dorian Gray picture. Okay. And this is kind of what we're doing. We're trying to take us at our age and stop and delay aging as much as we can. Scenario two is the Wolverines or the fountain of youth is to take old people and make them young again. And I'll tell you, this is not going to happen, at least not in the foreseeable future. It's like what I talked about, sarcopenia that is too late. But actually senolytic is an example for something that takes at least at mice. They are very old. You give them senolytics and their healthspan is improving, although their lifespan has not. Okay, but taking a person into a pool and then he comes young out is not going to happen. So the third scenario that I think is really the ultimate scenario is the Peter Pan scenario. Peter Pan doesn't grow old. And I think the idea that will soon still to be defined was soon will have an ability maybe to take a 20 year old person and basically rejuvenate him every month or every year and repeat it. So we delay aging enough in order to really pass a lot of the stages of diseases and maybe break the maximum lifespan of humans. That is about 115. Those are things that we're talking about. And by the way, I think the Peter Pan eventually will be the easiest thing to do. I think it's probably technically going to be the easiest thing to do, but what we need to do is to work on of that in parallel. Okay. It's not that we're saying let's just do what we think is good for the next, you know, to get to 115. I think we used to use our science in order to start advancing them and there'll be crossovers probably with time also.

That's fantastic. Well, I think I join our listeners in saying that we wish you and the other people working in the field the greatest possible success with those endeavors. Professor Nirbarzilai, thank you so much for your time and thoughts today.

Thank you so much. And for your organization. You've done really great leadership, took really great leadership role in this field and I appreciate that and that's why it's such a pleasure to be with you.

I know that Kristen and the rest of the leadership at Bio Age will be really proud to hear that you said that. Many thanks as well to our listeners and subscribers. If you have feedback or suggestions for future episodes of Translating Aging, you can contact us by email podcastyourage labs.com on Twitter @BioAge podcast or via our LinkedIn page. You can also follow our sponsor, BioAge Labs, on Twitter and LinkedIn. We'll see you next time.