Professor Kaeberlein, what is the future in aging research? Will we keep talking about Metformin, rapamycin, caloric restriction in the next ten years? What's new on the horizon? What is the direction that aging research is taking? And if I may ask, there are known unknowns, and then there are unknown unknowns. What are those in aging research?

Sure. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. So I think yes, we will continue to hear about rapamycin, Metformin, caloric restriction. There are a lot of people studying that. And you know, the pace of research that's going to continue to happen over the next five to 10 years. I hope that what we will start to understand is the degree to which any of these interventions can impact healthspan, probably not lifespan in people, but healthspan and people. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. And I think we will see that I think we will see, you know, true randomized clinical trials, and then also anecdotal reports and data collection on things like rapamycin and metformin for a variety of age-related indications, so that I'm confident will happen over the next five to 10 years. I think we will have a much better feel for both risk and efficacy for known unknowns like rapamycin or Metformin over the next five years. I think, you know, there are some areas that are exciting right now in the field but of unclear long-term utility and value and efficacy. So you know, one example of that would be epigenetic reprogramming. So there's a lot of excitement about that. So we know it. So let me just take a step back. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. We know with age that there are epigenetic changes that happen in a predictable way. That's where this idea of epigenetic clocks comes from that you can measure these changes in the epigenome. Because they happen in a predictable way, they can actually give you some information about chronological age, that's pretty clear, maybe about biological age. And so. So there are two things about that that I think are intriguing and worth paying attention to. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. One is the further development of epigenetic clocks in the broader context of aging clocks in general or aging biomarkers in general. So this will be a big area of investment and research over the next ten years. Can we develop personalized, individual predictive signatures that can tell you about your biological aging process at an individual level and potentially also tell you about efficacy for a given intervention, like rapamycin or caloric restriction? Is it working for you? Based on your personalized signature of biological age, we are far away from that. There are, unfortunately, unscrupulous people already selling things that they claim can do that. They're lying to you. They can't. But I think I think we might get there in the next five to 10 years. So it's quite early days in the aging clock field. But I think that's worth paying attention to. And I think there will be progress made in that area. But related to that, specifically, is the epigenetic aging and the changes in the epigenome that happen with age. There's a lot of enthusiasm and interest around the idea of reversing that. And that's where the epigenetic Yamanaka factors come in, right, the idea that we can restore epigenetic marks to something that looks like the youthful epigenome and potentially rejuvenate function in cells and tissues in an aged animal or eventually in an aged person. So that's an area that lots of people are interested in. I'm sure many of your viewers are aware that altos labs, you know, has, that's what they're focusing on. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. 

And so they clearly believe that there's, you know, the potential there, not just foraging, but for maybe a variety of regenerative uses in humans. So I think that will be an area to pay attention to that's a no an unknown, right. We know that this is possible in cells. It's unknown whether it will be feasible in animals or people. And feasibility. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. I think there are two components to that one. Does it actually work? Can you significantly restore healthspan or extend the lifespan in a mouse or a person using epigenetic reprogramming that has not been done yet? And then secondly, even if you can, is it going to be safe? Are there going to be unintended consequences that will, from a pragmatic perspective, make it not useful for that kind of application? So that's an unknown, you know, we'll just have to wait and see, my feeling is that we'll probably be able to, we'll have a much better idea of that, in five years, certainly in 10 years, we may not even completely know the answer to that, you know, in that timeframe. So, I think that's an area that I'm paying a lot of attention to, and we'll just have to see, you know, there's going to be a lot of investment in that space. And so I think rapid progress will be made, I kind of put stem cell therapies in that same category. Although those are a little bit more developed, it still really is, is, you know, unclear. And there's not a lot of great data, in my mind, supporting the idea that stem cell therapies can have a robust effect on function or lifespan, yet, but I think there are a lot of people looking at that, and it makes sense. And so, you know, we'll know more in the next five to 10 years. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. So what are the unknown unknowns? Um, you know, I think that's hard to answer. Right? Because it's unknown, I think, in a general sense, you know, a question in my mind is whether or not we are going to see, you know, what, what I would consider a major paradigm shift in the field. And I don't I. I won't, I wouldn't say I, I am optimistic that that's going to be the case, I think, you know, we have to recognize that the world is changing at an accelerating pace, right and that there are new technologies being developed all the time. And so I think there's the possibility that there will be some major discovery that that is unanticipated, that will sort of change the playing field, right. I think right now, you know, with things like rapamycin and metformin, and the various pharmacological or genetic interventions that people are studying, you know, it's optimistic to think we're going to do better than a decade or two in humans of healthspan. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. Not saying it's impossible, but that's kind of what I would predict. We'll see what epigenetic reprogramming can do. But I am not optimistic that it's going to do any better than the current sort of collection of interventions that people are studying. It may not even be as useful. So will there be something that, you know, that's paradigm-changing, and you can get beyond that? That I think is, you know, impossible to answer. But there's a possibility that that will be the case. And I can't say what it will be, because it's an unknown, but, but I think it could happen. And I hope it does because I think that'll you know, that that'll just make this entire space, more exciting and more relevant. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. But I don't want to diminish the impact. If we are successful at enhancing human healthspan for the typical person by 20 years, that's a big deal. And I think that it's important to appreciate the impact that would have in and of itself, and that I think is very realistic. I will be disappointed if we can't have that impact, given where we're at today. So I don't want to diminish the value of targeting biological aging using the strategies that people are using today. And the potential impact that could have on society and quality of life for, you know, hundreds of millions of people and their pets. Right. So I think it's important to, you know, keep that in perspective that that's a that's a really valuable and important thing to continue to pursue. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD. 

Well, ten years of additional healthspan is certainly, you know, would be a huge price. And that's important than it's important to the stress of healthspan, not just of lifespan. That's right. Dr. Matt Kaeberlein, PhD. Dr. Anton Titov, MD.