Future Directions in Anti-Aging Research: From Rapamycin to Epigenetic Reprogramming

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• Current Interventions and Future Clinical Trials
• Epigenetic Clocks and Aging Biomarkers
• Epigenetic Reprogramming Potential and Challenges
• Stem Cell Therapies for Aging
• Potential Paradigm Shifts in Longevity Research
• Healthspan Impact on Society
• Full Transcript

Current Interventions and Future Clinical Trials

Dr. Matt Kaeberlein, MD, PhD confirms that rapamycin, metformin, and caloric restriction will remain central to aging research. He tells Dr. Anton Titov, MD that the next five to ten years will bring crucial data. Researchers will conduct true randomized clinical trials for these interventions. The focus will be on understanding their impact on healthspan rather than lifespan extension.

Dr. Kaeberlein expects much better data on both risks and efficacy. This research will provide clarity for age-related indications. The field will move beyond anecdotal reports to robust clinical evidence.

Epigenetic Clocks and Aging Biomarkers

Epigenetic changes occur predictably with aging, forming the basis of epigenetic clocks. Dr. Matt Kaeberlein, MD, PhD explains these clocks measure biological aging processes. He discusses their potential for personalized aging assessments during his conversation with Dr. Anton Titov, MD.

The next decade will see major investment in aging biomarker development. Researchers aim to create individual predictive signatures. These could eventually show if anti-aging interventions work for specific people. Dr. Kaeberlein cautions that current commercial claims about biological age testing are premature.

Epigenetic Reprogramming Potential and Challenges

Epigenetic reprogramming using Yamanaka factors represents a cutting-edge approach. Dr. Matt Kaeberlein, MD, PhD describes the excitement around restoring youthful epigenetic marks. This technique could potentially rejuvenate cells and tissues in aged organisms.

Dr. Kaeberlein outlines two critical unknowns about epigenetic reprogramming. The first is whether it can significantly restore healthspan or extend lifespan. The second concerns safety and potential unintended consequences. Companies like Altos Labs are investing heavily in this research area.

Stem Cell Therapies for Aging

Stem cell therapies occupy a similar emerging category as epigenetic reprogramming. Dr. Matt Kaeberlein, MD, PhD notes these therapies are more developed but still lack robust data. During his discussion with Dr. Anton Titov, MD, he expresses caution about current claims.

Evidence supporting stem cell therapies for function or lifespan extension remains limited. However, many researchers are actively investigating this approach. Dr. Kaeberlein anticipates more conclusive data within the next five to ten years.

Potential Paradigm Shifts in Longevity Research

Dr. Matt Kaeberlein, MD, PhD considers the possibility of major paradigm shifts in aging research. He acknowledges that new technologies develop at an accelerating pace. Unexpected discoveries could completely change the anti-aging landscape.

While current interventions might extend healthspan by decades, breakthrough technologies could achieve more. Dr. Kaeberlein remains open to these possibilities while maintaining realistic expectations. The unknown unknowns of aging research could yield transformative approaches.

Healthspan Impact on Society

Extending human healthspan by 10-20 years would represent a monumental achievement. Dr. Matt Kaeberlein, MD, PhD emphasizes this would dramatically improve quality of life. He tells Dr. Anton Titov, MD that this goal is realistic with current research directions.

Such advancements would benefit hundreds of millions of people and their pets. Dr. Kaeberlein stresses the importance of healthspan extension over mere lifespan increase. This distinction ensures people enjoy additional years in good health rather than prolonged decline.

Full Transcript

Dr. Anton Titov, MD: 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?

Dr. Matt Kaeberlein, MD: I think yes, we will continue to hear about rapamycin, Metformin, and caloric restriction. There are a lot of people studying that. The pace of research is going to continue to happen over the next five to 10 years.

I hope that we will start to understand the degree to which any of these interventions can impact healthspan—probably not lifespan in people, but healthspan. I think we will see true randomized clinical trials, and also anecdotal reports and data collection on things like rapamycin and Metformin for a variety of age-related indications.

I'm confident that will happen over the next five to 10 years. We will have a much better feel for both risk and efficacy for known unknowns like rapamycin or Metformin over the next five years.

There are some areas that are exciting right now in the field but of unclear long-term utility, value, and efficacy. One example of that would be epigenetic reprogramming. There's a lot of excitement about that.

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—you can measure these changes in the epigenome. Because they happen predictably, they can give you some information about chronological age, and maybe about biological age.

There are two things about that I think are intriguing and worth paying attention to. One is the further development of epigenetic clocks in the broader context of aging clocks or aging biomarkers in general. 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. Unfortunately, unscrupulous people are already selling things that they claim can do that. They're lying to you—they can't. But I think we might get there in the next five to 10 years. It's quite early days in the aging clock field, but I think that's worth paying attention to.

Related to that specifically is 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. That's where the epigenetic Yamanaka factors come in—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.

That's an area that lots of people are interested in. I'm sure many of your viewers are aware that Altos Labs is focusing on that. They clearly believe that there's potential there, not just for aging, but for maybe a variety of regenerative uses in humans.

I think that will be an area to pay attention to—that's an unknown. We know that this is possible in cells. It's unknown whether it will be feasible in animals or people.

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 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—we'll just have to wait and see.

My feeling is that we'll probably have a much better idea of that in five years. Certainly in 10 years, we may not even completely know the answer to that in that timeframe. I think that's an area that I'm paying a lot of attention to, and we'll just have to see.

There's going to be a lot of investment in that space, 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 unclear.

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. We'll know more in the next five to 10 years.

What are the unknown unknowns? I think that's hard to answer because it's unknown. In a general sense, a question in my mind is whether or not we are going to see what I would consider a major paradigm shift in the field.

I wouldn't say I am optimistic that that's going to be the case. We have to recognize that the world is changing at an accelerating pace and that there are new technologies being developed all the time.

I think there's the possibility that there will be some major discovery that is unanticipated that will change the playing field. Right now, with things like rapamycin and Metformin, and the various pharmacological or genetic interventions that people are studying, it's optimistic to think we're going to do better than a decade or two in humans of healthspan.

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 collection of interventions that people are studying. It may not even be as useful.

Will there be something that's paradigm-changing and you can get beyond that? That I think is impossible to answer. But there's a possibility that that will be the case. I can't say what it will be because it's an unknown, but I think it could happen.

I hope it does because that will make this entire space more exciting and more relevant. 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.

It's important to appreciate the impact that would have in and of itself. I think that is very realistic. I will be disappointed if we can't have that impact, given where we're at today.

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 hundreds of millions of people—and their pets. So I think it's important to keep that in perspective—that's a really valuable and important thing to continue to pursue.

Dr. Anton Titov, MD: Well, ten years of additional healthspan would certainly be a huge prize. And it's important to stress healthspan, not just lifespan.

Dr. Matt Kaeberlein, MD: That's right.