Longevity Panel - The Scientists working on Reversing Aging

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A couple of weeks ago Avi Roy, alongside Nathan Cheng & Laura Minquini, hosted the Longevity Panel discussion, which assembled some of the biggest scientists in the field currently working on reversing aging.

This discussion was intended to illuminate how they are approaching longevity and to know if we are any closer in achieving it.

The talk was split into two sections: the first being open discussion guided by questions from the hosts. The talk was then opened up to the floor, allowing audience questions. Part 1 will provide the transcript from the first section of the Longevity Panel. Enjoy!

The hosts:

Laura Minquini – the founder of MYKIGAI, a DTC longevity platform dedicated to the education, vetted curation and management tools for people to get on board with longevity as a lifestyle. Having spent most of her career in trend forecasting and branding design and fashion products she sees the potential of longevity becoming the next big consumer category empowering people to take their health in their own hands.
Avi Roy – a biomedical scientist and entrepreneur based in Oxford. He advises and funds startups in the health and longevity space in North America, the EU, and India. He also work with governments to develop and refine policies that enable the longevity infrastructure.
Nathan Cheng – the founder of the Longevity Marketcap Newsletter, a once a week roundup of the developments in the longevity biotech industry. He is also the founder of Longevity List — a website where you can find jobs, companies, and investors in the longevity biotech industry.

The panel:

Alexandra Stolzing – the head of research at SENS research foundation and Professor at Loughborough University. Her research focuses around the amelioration of the hallmarks of aging.
David Sinclair – a Professor of genetics and co-director of the Paul F. Glenn centre for the biology of aging at Harvard medical school. Devid is also the author of ‘Lifespan‘, and his research focuses on understanding and slowing the pace of aging through a variety of approaches.
Liz Parrish – the founder and CEO of Bioviva sciences. Liz’s focus is the advancement of gene therapy for the purpose of extending healthy lifespan in humans.
Aubrey de Grey – the chief scientist officer and co-founder of the SENS research foundation. Aubrey is a biomedical gerontologist, author of ‘Ending Aging‘ and one of the longest proponents to study the field of longevity.
David Gobel – the co-founder and CEO of Methuselah foundation. David’s focus is establishing and supporting research, breakthrough technologies, and regenerative medicine.
Joao Pedro de Magalhaes – a microbiologist and Professor at the University of Liverpool. The goal of Joao’s work is to understand the genetic cellular and molecular mechanisms of aging across all organisms.
Jean Hebert – Associate Professor in the department of genetics at the Albert Einstein college of medicine, and author Replacing Aging. Jean spends his time devising methods of cell replacement for the adult neocortex, where its cells are lost due to damage or age-related to degeneration.
Greg Fahy – the vice president and chief scientist officers of 21st century medicine and founder of Intervene Immune. Greg is also a cryobiologist, biogerontologist, and businessman based in California. His research focuses on organ cryopreservation by vitrification.

The questions:
(The timestamps relates to when the question in asked in the full video)

05:35 – How do you plan on reversing aging?

14:52 – If we want to reverse aging or slow it, what are the most promising approaches to measuring biological aging and the effectiveness of the therapeutic interventions that we’re developing?

28:28 – In 1969, gerontologist Alex Comfort suggested that life expectancy, not simply maximum lifespan, could be extended to 120 years within the next 20 years. That didn’t happen because he obviously is not with us anymore. What will be different this time as we try to get people interested in longevity or promise them that this is imminent in some way or form?

42:53 – What are two or three things that you intrinsically believe are inevitable in the future of longevity/aging/health within the next decade?

Here’s what was said:

05:35 – Avi Roy: Thanks Laura. Thanks for doing the hard work of introducing everybody. Although everybody here probably is very well known by all the people in the audience and worldwide. So I’m going to begin with a rapid fire question. So please keep your answers as succinct as possible. I’m sure many people have asked you this question before, but how do you with your research and your work and the companies that you advise, how are you plan to reverse aging?

And so that everybody doesn’t jump in at once. Maybe we can go ladies first and with first names, Alexandra, do you want to go first? How do you plan to reverse it?

Alexandra Stolzing: Thank you for the question. Yes. How do I want to do it? And so I work for the SENS foundation our paradigm has been to reverse damage that has accumulated with aging, and we have a couple of these like damages in our body and we have projects that try to reverse them. And apart from the science bit, being out and about and informing the public and talking about it, I think is the other thing that would really help us reversing aging. And I’ll leave it at this point.

Liz Parrish: Okay. I think that’s probably next. I’m the only other lady here, outside of Laura. BioViva is committed to reversing aging through gene therapy. A lot of people probably know that if you don’t check it out, it’s pretty cool. And we are, we have developed a new vector delivery system that can deliver multiple genes, decent sized genes, and so we hope to deliver the first mini-artificial chromosome to work as a protector, maybe something like a vaccine against aging, but we’re really looking to upregulate regeneration more than the degeneration at the cellular level. So we go after the hallmarks of aging and by doing that, we hope to accomplish our task of not only slowing or stopping aging, but reversing it.

Avi Roy: Fantastic! Aubrey?

Aubrey de Grey: Yeah. So Alex, more or less that it’s, I delighted to have Alex on our team at SENS research foundation. We are interested in repairing the various types of damage of aging, which have been of course described in classified in various ways, by various authors over the past 20 years.

But that doesn’t really change the priorities in of what we need to develop. We are, at the foundation, working on the most challenging aspects of that, because both of the aspects that other people whether for financial reasons or other reasons have been neglecting, and our business model is essentially to work on damage repair of a particular type for as long as it takes to get to the point where it becomes investible.

At which point we spin projects out of startup companies. And so of course we work very closely with the private sector and the eventual goal is to be able to apply many of these therapies to the same people at the same time. So as to keep all aspects of their accumulation of damage within the threshold level that the body is able to tolerate, and to prevent, and preempt, all of the health problems the late life.

Avi Roy: Thank you. Either of the David’s.

David Gobel: I will yield to David Sinclair first.

David Sinclair: Thanks, David. So we’re pretty excited in my lab about reversing aging through epigenetic means. So this is what we call partial reprogramming. We published a paper in December about the use of three of the Yamanaka factors to restore eyesight in old mice and mice that had optic nerve damage.

And we’re continuing to use that technology to tick off the various tissues and organs in animals to see which ones can be rejuvenated from old age deterioration. And so we’re looking at that, we’re doing a number of screens to figure out how this actually works out.

As a possible, there’s a backup copy of a youthful epigenome in mammals, and we’re working towards clinical trials, which will head into primates by the end of this year. With the goal of a trained blindness initially, but ultimately having hopefully some more molecules and other easier treatments than gene therapy to reverse either individual tissue aging or whole body.

Avi Roy: Thank you. David G…?

David Gobel: So Methuselah foundation is in the business of identifying holes and filling them. The first hole, we filled in partnership with Aubrey, when Aubrey was my co-founder at Methuselah foundation, the first hole was: no scientist could actually pursue this project we’re on without losing their career, and we had a Methuselah mouse prize and Aubrey’s presentations in the public, the book that turned that situation around. And now it’s an inevitability.

The next hole was that it needed to be investible. And so we started Methuselah fund, and that started what we hope and think has become something of a reference portfolio. In the portfolio are epigenetic reprogramming as David Sinclair mentioned, turn.bio out of Stanford, senescent cell ablation. We’re partnered with the SENS foundation, in Ocean Bio and with or on Oncosenics, excuse me. So those are just a couple of examples. The next hole was associated with our strategy of new parts for people. You can get parts for an old Corvair, 1961 Corvair, but if you need new parts for people, you can’t do it.

You gotta get plastic and titanium, and ceramic. I think that’s ridiculous. So we partnered with NASA to create a solution to the rate limit for scaling up 3D printed tissues to macro-sized tissue. And that was just won last week – it exists, the hole has been filled. Of course, there’s lots of little holes around it that need filling, but that is a breakthrough of titanic proportions.

And I don’t mean the sinking Titanic either. So that’s what we do, we find holes and we fill them. There’s still plenty of holes to fill.

Avi Roy: Thank you, David. Greg…? I think Greg has just dropped off. Would you like go Jean?

Jean Hebert: First, thanks for having me. Yes, I come from the perspective – echoing a bit what Alexandra said about damage – but I come from the perspective that the complexity of macro molecular damage that occurs with age and it’s really, well-documented really mandates a tissue replacement as an essential component to beating aging.

And, as you’ve just heard from David G, that’s underway for lots of parts of the body. A lot of people are interested in that. But what we’re focused on is the neocortex, the part of the brain that we use for our highest cognitive functions. And we’re taking sort of a ‘Ship of Theseus’ approach, where we plan on progressively being able to replace the whole neocortex over time, piece-by- piece of tissue by piece of tissue and the proof of concept that this should work is already well-established due to the nature of how the neocortex works, it’s a very plastic substrate. The execution, however it is far from being achieved. So there’s a lot of work that needs to be done there, technical hurdles. And those are the things that we’re working.

Avi Roy: Thank you. Joao, our final participant for the answer.

Joao Pedro de Magalhaes: Yeah. Sure. Thank you. Pleasure to be here. So I would say on one hand reversing aging, I would like to understand the mechanisms of aging. Why do we age? What are the molecular cellular genetic mechanism range? What’s the driver of aging? So that’s one of the things I’ve been working on.

I don’t think we understand the process of aging. I’ve just put up this pre-print criticizing the hallmarks of aging as a paradigm. So not, I think Hallmarks of Ageing is a wonderful review, but I don’t think it explains aging. I don’t think it’s the dogma of the field of aging that sometimes people perceive it as. I’m not even sure damage causes aging.

So, I don’t think we understand well the process of aging and in order to intervene and to reverse it, I think we need a better mechanistic understanding of aging. So that’s one of the things I’ve always been interested and I’m still working on in my lab. In addition to that I also work with several companies, technology development in particular.

In particular, I’m also the CSO of Sentara, which is a Swiss based company when developing new technologies and particularly for artificial chromosomes and gene therapies. The idea is that if we can, even if we can figure out why we age and we need to do it to actually develop the therapies and that’s not straightforward.

So we’re also working on developing the technologies that hopefully one day would allow us to reverse aging. And lastly, I’ve always done outreach and I’ve always been interested in spreading the word of the importance of research on aging. I don’t think that’s as necessary than when I was started, more than 20 years ago, because now there’s lots of websites and lots of advocates, but that’s something I still do.

Avi Roy: Thank you Joao. Nathan, next question.

14:52 – Nathan Cheng: Hey, thanks Avi, and thanks to all the panelists for your responses. So for our next question, I’d like to start off so Siddhartha Mukherjee writes in his book ‘The emperor of all maladies’ that science begins with counting. So if we want to reverse aging or slow it, what are the most promising approaches to measuring biological aging and the effectiveness of the therapeutic interventions that we’re developing? So this question is open to anybody on the panel. Maybe we’ll start with David Sinclair.

David Sinclair: Great. I’m talking from my car. Hopefully you can hear me okay. So we are a field that has had a real breakthrough in the last decade with the discovery of the epigenetic clock, it was really good. The first truly accurate measure of biological age. There are more now, there is the glycan age, there’s an immuno-age, there’s a proteome that you can look at.

But I’m still a big fan of the accuracy, and the underlying biology of the DNA methylation, also known as the Horvath clock. That is a pretty good predictor of future health, both in animals and in people, and now across species, and the fact that you can use the same clock to look at aging and bats and sheep and dogs and humans. It’s quite a remarkable thing that Steve Horvath has shown us. So that’s the best one, and do a bit of a reveal here, my lab does work on lowering the cost of that test. We’ve made some breakthroughs, and we are looking to commercialize that in the near future, to democratize it.

So that people will be able to monitor their biological age, which I think is actually just as important, if not more important than their actual age.

David Gobel: May I take a stab?

Nathan Cheng: Yes, please.

David Gobel: So I come from an additional viewpoint. Not clocks. But the fact that we have as mammals an excruciatingly sophisticated methodology of finding those who are young and fertile.

We look at body plan and the face. And so for me and our organization, we look for empirical and functional results, i.e. we know it when we see it. We are very much against the ‘we’re going to take 130 pills and hope for the best’ route. Our view is if you’re already old, let’s say that 50 means you’re on a decline, if you don’t feel better because of an intervention, either prospectively, or actually, then is it really doing anything? Now, scientifically the numbers may be better, but I argue that perhaps you don’t know what the numbers mean yet. For instance, in 1974, the United States won on a tirade to make sure that our cholesterol was down low and that the numbers were supremely important, and now we’re finding out, oh, wait a minute it was inflammation. So I follow what the Supreme court justice said when he said “I don’t know how to define pornography, but I know it when I see it”. So we focus on things like skin improvement, deep skin improvement, functional improvement, muscular improvement.

The reason that we invested in turn.Bio out of Stanford, was because their results were functionally apparent, it was unarguable. They worked better, stronger, and the bones healed faster. So we know it when we see it is our clock.

Liz Parrish: I agree with the epigenetic clock. BioViva we have a clock now that offers people five different results based on different peer-reviewed agreed upon clocks.

And I think that the epigenetic clocks are great. But I do the immune clocks. I like all of the things that both of the David’s talked about. There is also cognitive function, and those tests are getting better. And I think they’re going to be really important. You’re going to see that come out in one of the papers that we’re going to be releasing soon.

And then as to David G, the what’s happening inside the body is as important as what’s happening outside. When you’re looking at treating aging you may have to start with an eye and the case of David S’s case, or you may have to start with a kidney. Some of us would like to start with the whole body. And the truth is that in order to cure aging, you’re going to have to be able to target every tissue.

Now, in some cases, we might have better results with certain areas of the body or not, and the great thing about treating traditional disease is it gives us the ability to have end markers that we know what we have to meet. Whilst the better biomarkers of aging are developed. But speaking to that, inside and outside of the body, the MRI images of an old and a young person are very evident, and actually, Avi this speaks to one of the brilliant ideas that you had some, I don’t know, five or 10 years ago, which was like creating an encyclopedia of the slices, the cross-sectional analysis of MRI images throughout a human body, because the brain, the liver, the organs, they all change.

And so it’s not just on the outside it’s all the way through. So some sort of cross section and with some of the gene therapies we do that we actually pick imaging because we want to see all the way through if there are any changes. So I think that’s going to be an important marker coming up.

Jean Hebert: Can I build on that? Maybe? The imaging idea, I think is very good especially for certain parts of the body, like the brain. We do two photon imaging to look inside the brain, the live brain, and we see in model animals, and no reason to think it would be different in humans, that the you know, light penetration and diffraction starts deteriorating as soon as you reach adulthood. And then the longer you go, the worse it gets, it’s this very measured phenomenon. And it’s also interesting that it’s very it can be disconnected completely from cognition, so I’m not so sure it cognition is a good measure. So there’s a lot of things that will reverse cognition to what is considered a younger performance stage. Caffeine, for instance, for a lot of people improves their cognition and, but does that really reverse aging?

And we look, if we look at this less performance based but more anatomical based imaging method, we see that aging is not reversed even though cognition or the performance is. So I think we have to be careful about what we’re measuring because yes, maybe we’re improving performance, and that’s great, and we should do that. But we’re not necessarily reversing the aging process, however you define it, I would define it as the accumulation of damage. And that’s pretty apparent in the brain because of this light diffraction that occurs progressively over time. We might be able to improve our quality of life to a certain extent, to a certain age, but if this accumulation of damage goes unimpeded we hit that wall at around 100-120 (years old) and that’s actually been calculated for certain molecules that don’t turn over much like elastin or don’t turn over at all.

The vasculature can’t survive past a 100-120 years without being replaced. But that’s, generalizable for other aspects of tissue structure and tissue components. So you have to be a little weary I think of performance as a measure of age reversal, and try to be stick to more biological, molecular, or anatomical measures.

David Gobel: I’d like to jump in and make a quick comment.

One of the problems of our field is funding. If you want to get fast funding, help people look and perform younger, and the funding will come in like a flood. I don’t speak against what you said technically though Jean.

Aubrey de Grey: Yeah. I think one of the important things to highlight here is that even though we have become very much better, in the past decade, at developing clocks of aging rating of one sort or another, in other words, predictors of how soon you’re going to start suffering from the health problems of late life, that are based on large quantities of data that were previously technically inaccessible. Even though we’ve got enormous progress there, what we still are really at square one on, is identifying clocks that can be validated in the context of interventions. In other words, clocks that can reliably be assumed to give us good information, advanced information, regarding whether an intervention is working. Of course, it’s very true that we want to be predicting that before there is any substantial functional decline, ideally before there’s any substantial cosmetic decline, to go back to what Dave just said, but we might be getting there. But in the context of actually, whether an intervention will break the clock will be uncoupled from the clock, in other words, whether the clock will actually reliably tell us whether the intervention is working, I think we’re still very much at the very early stage.

Nathan Cheng: Okay, thanks for that. Oh, okay. Greg welcome to the stage. We missed you a little earlier. Maybe you can answer this question and at the end you can maybe just tell us a little bit about your sort of perspective on how you were reversing it.

Greg Fahy: Sure. And I apologize, I had a little technical difficulty ringing in before.

Yeah. So just to pick up on some of the things that have been said Intervene Immune. We are actually using interventions that can be applied right now to do things like epigenetic programming, but by changing the signals that a cell sees in the body so that their instruction set for how they should behave changes in a more youthful direction.

And we’ve been trying to reverse the aging of the immune system by regenerating the thymus, but in the process of doing that, we’ve also found that a epigenetic aging has been going in reverse in our treated volunteers based on all four of the standard clocks, plus a plasma-based clock that we applied retrospectively to our data set recently after our first clinical trial.

So to marry that information with what’s been discussed, I think we have an example of situation in which you see both performance enhancements and epigenetic clock reversal just by changing the signaling paradigm that the body is being subjected to. And we have people saying that they feel great subjectively, but then objectively we see things like kidney improvement, reduction of prostate cancer, risk improve lung function, and all kinds of other things that can be objectively measured.

So we have both the performance/subjective aspect looking good, and the object of epigenetic clock based measurements looking good as well. And our goal is to do something about aging in the near term and not have to wait for the development of much more sophisticated therapies in the future, because we’re all aging now and we need some answers sooner rather than later.

Nathan Cheng: Great. Thank you, Greg. Is there anybody else wants to chime in. Joao Pedro? Alexandra?

Alexandra Stolzing: Let me just some very short comments. We need more clocks, even though we have a couple of very good clocks already in the market, I think we need more. And we need them cheap as mentioned before, and we need them so that everyone at home can have them as well. That would be really like helping a lot with like clinical translation.

If people don’t have to come in for an in very intensive or expensive measurement. So it would be really great and having positive markers, or something that is actually involved, as Pedro said, like in how will your aging, like knowing that your marker is actually involved in that process would be really nice.

So yeah, we need more of them.

Joao Pedro de Magalhaes: So yeah, I don’t have much to add. I agree with David Sinclair, that the epigenetic clocks is the most reliable now, and it’s also fascinating how particularly now this preprints wrote from Steve Horvath of how it works across mammals. I’m still trying to get my head around it, I think it’s incredible.

But I would agree with Aubrey. In fact, Aubrey once said that the major outcome of aging is of course death. So that’s what we need to predict. And although there are epigenetic clocks, I think there’s Grim age, for instance. I’m not sure we know enough to do a clinical trial based on it. So we still have some way to go before we can use this for for trials.

Greg Fahy: I guess I just need to say that, we did observe a reversal of GrimAge in the TRIIM trial that we did, and we are now launching something called TRIIM-X, and we have preliminary evidence, at least based on the plasma clock, that we’re seeing similar effects.

But we do plan to emphasize the GrimAge clock as something that can be modified by an available intervention going forward. So I do think that there’s actually a lot of potential for using GrimAge clock for monitoring the course of clinical trials in the near term.

Nathan Cheng: Okay, great.

Thank you for all your answers. I’m going to hand it over now to Laura for the next question.

28:28 – Laura Minquini: Thanks Nathan. So I’d love that David Sinclair mentioned about the democratization of some of these tools that people will be able to use for, to look at something like the biological age, which as you mentioned, is more important than your chronological age, because that’s your health, your actual health.

I have a question for the panel because I know that longevity science, though it’s really advancing in the last twenty years, people have been talking about this for a long time. In 1969, gerontologist Alex Comfort suggested that life expectancy, not simply maximum lifespan, could be extended to 120 years within the next 20 years.

That didn’t happen because he obviously is not with us anymore. What will be different this time as we try to get people interested in longevity or promise them that this is imminent in some way or form? And this is a lightning round questions so if the panelists could give a succinct answer to how we can get people to believe that this is a possibility.

David Gobel: I’ll jump in first and say that the largest, most wealthy generation in history does not want to go quietly into that good night.

And they are more and more going to be putting their money into this. So it’s going to be raining and the floods. Number two, look at the size of the audience of this clubhouse and the quality of the presenters. There is no snake oil here.

Liz Parrish: I’d like to thank you, David. That’s awesome. I’d like to add to that, that unlike the 1960s, the 1970s came on and actually some amount of evidence started to come on that we could actually modify organisms at the genetic level and we started to see then thereafter, the first model organisms that had extended lifespans and we continue to do that. And we’ve gotten better at looking at the natural world and identifying what’s happening with certain organisms that live very long, outside of humans. And so that gives us the ability to be a lot more confident plus you’re going to see there’s going to be a lot of human data coming out over the next few years.

They’re going to show certain areas of age reversal and certain persons, sorry. I was running to an appointment and that’s going to, Greg Fahy, for instance, with his thymus regeneration, he showed some age reversal, you’re going to continue to see that in human work, human studies, and in the biohacker community.

So I think that this is the time that we’re going to get a platform to take off. I think that we do have the technology that can extend human lifespan to the point of getting that takeoff velocity that Aubrey talks about, but we have to get out there and we’ve got to get in into humans and we actually have to use it.

I don’t think that we can afford another mouse study. They’re not good predictive models of humans, and we now need that human evidence. So my hat goes off to all of you out there who are getting and collecting good data. Thanks.

Aubrey de Grey: Yeah. I’d like to agree with Liz about the relevance, and the critical relevance of human data, but we must also go back and ask ourselves what we are able to flee from laboratory data.

And I think a large part of the problem. That is encapsulated in the question, a large part of what does make things different now is still ongoing. Namely, we have more and more areas where we can point to dramatic progress. But then other areas where we can’t. So to put extreme examples, we can take nematode worms and make them live 10 times longer than they normally do just with a single genetic intervention.

But if we look at mice, the amount that we can extend the lifespan, whether the mean or maximum, is pretty much the same as it was in the 1930s, when Clive McCay discovered the benefits of calorie restriction, which is not a cause for optimism. We have to, I think, accept that we still have a way to go in providing a really coherent body of data and a message to humanity to really justify the claim that we are on brink of dramatic breakthroughs.

And maybe we’ll never get there. I think one way of saying what Liz just said is that maybe the youth utilities of animal model is just not sufficient. And we will actually just get there by getting there with humans in terms of convincing humanity that it is possible.

Joao Pedro de Magalhaes: I would just add that, in addition to the genetic manipulations, there has been a lot of progress in animal models in pharmacological level. So I am fairly optimistic about developing longevity drugs, and I’m sure you’re aware of a lot of folks that are working in this area in several companies as well.

Now that’s still far away from reversing aging. But at least we can show that in animal models, we can delay aging with pharmacological interventions, and I think that can serve as an impetus to, to say we need more studies in this topic to have even more impactful therapies.

David Gobel: Since the topic of human models has been brought up, Methuselah foundation’s portfolio companies: Organovo and Visciant Bio, already use human tissue constructs in searching for and validating small molecule drug interventions.

And so it isn’t something that’s coming, it’s something that is here. So as it’s been said, the future is already here, it’s just not evenly distributed. And so that is something that our foundation, Methuselah foundation, is going to be working with NASA on as a next step in our tissue challenges series.

David Sinclair: Actually, David, I agree with you on that. The exciting thing about the future is that a lot of it is here. So I’m sitting here with a biosensor, just stuck on my chest, that’s reading my vitals a thousand times a second. I’ve got this ring on it, I’ve got a watch. I have blood tests. I can do mouth swabs. It’s just the beginning of being able to monitor ourselves to know ,sometimes years in advance, whether we’re going to get sick or not.

I don’t think in the future, people will die from heart attacks very often because of these devices. But what’s exciting about this world that we’re very rapidly moving into – and this device, by the way, now that I’m wearing there were many companies working on this and doctors use them to send patients home early from hospitals, so that’s a huge saving – but what we’ll see is you can stick these devices on a million people and take a million swabs, or blood samples, and process those. And combine that with the medical records, and either supplements or drugs that they’re taking either in small cohorts or just because that’s what they want to do, we are going to learn so much over the next decade. And I know we don’t have a decade, but when you have a million, and a lot of them are going to be old and frail. We’re going to learn so much just by these massive experiments that are becoming within grasp in terms of the cost to be able to carry them out.

Jean Hebert: If I could add something. Laura, I think the way you framed the question right, was how we’re going to get enough of the population to reach a 100-120, somewhere between there. And for that, I think a lot of what the panelists are talking about, there’s a good reason to be optimistic.

But I think we use the term age reversal a little too loosely, again, referring to performance measures or markers that have not really been validated in the sense of age reversal. Where, if you reverse age 20 years, you live 20 years longer. I think, again, those are more related to, just the certain states of performance or states of physiology, or cells, but not necessarily the core of aging.

And as Aubrey pointed out earlier, these haven’t a lot of these markers, although excellent for measuring the biological age are not necessarily validated or haven’t been validated yet for rejuvenation. But I think we can do better than 100-120 years.

I think we can beat aging. The things that David G. has been alluding to with human tissue constructs, there’s a lot of interests, a lot of progress being made there. And yes, they’re great for testing drugs, but they’re even better for replacing the old body parts that, you know, in the elderly with the young ones that, that will reverse all aspects of aging and biological age. All the forms of damage which are known to cause all these other things, hallmarks of aging.

So I’m hoping, more in that direction will lead to more optimism in terms of, just breaking the cap off of the 100-120 year maximum that we’re talking about.

Greg Fahy: I think I want to just agree that the meaning of the epigenetic clocks needs to be revalidated.

So the clocks had been developed to sort of correlate with data that already exists, but if reversing the clock actually reverses aging or aspects of aging, we need to be able to show that by measuring aging in some other way. So one of the things that we’re doing is to see if we can link GrimAge changes to changes in coronary artery calcification, or cardiopulmonary exercise testing capacity, because these things predict your longevity over time and in the fairly near future too.

If your exercise capacity is much greater, and if we can actually increase that and show the grim age is reduced exercise capacity is increased. That would be pretty strong evidence that these therapies are actually working in the way that we hope that they are to actually reverse aspects of aging.

There’s actually evidence in population studies that metformin use can reverse coronary artery calcification, which is a leading cause of heart disease and death, and that’s part of our cocktail. So we have some hopes that we’ll be able to show these functional, or let’s say risk factor improvements, that should be able to independently predict that the risk of death and hopefully agree with the predictions made by these clocks, but it’s still early days.

Laura Minquini: Thank you for that, everyone. I wanted to say that my question was centered around the idea of, I am very interested in getting people wanting to have to seek longevity or to have it as a lifestyle. So the reason I asked this question was because if we promise people 120 years or more of life right now, are we promising them something realistic versus if we say you’re going to live longer with healthspan, within your life’s current lifespan, they might be more inclined to join our longevity lifestyle. And that’s why that was the direction more that I was thinking. But I loved all your answers, David,

David Gobel: To reply to your question directly, January 15th, I decided that it was time for me, at the age of 67 my own dog food.

Under doctor’s care, I started taking episodic rapamycin, metformin, fisitin, melatonin. I’ve lost 35 pounds. I had the gate speed of a 90 year old. I now am below the measurement point where people would be bothering to test my gait speed. I can do a pike and an L sit without worrying about it.

The speed of my thinking has improved. Basically when people see me, especially after the pandemic, they say “Wow, what’s happened to you?”. That’s what’s needed Laura! Mere civilians looking at you and said “Oh my darling, you look so wonderful. What have you done?” And then we get to tell them!

Laura Minquini: Longevity! Definitely David, I fully agree with you.

David Sinclair. You wanted to say something.

David Sinclair: My first thought was well done, David. That’s fantastic that you’ve done that and you’re a real role model for everyone. I was curious whether you’ve measured yourself before and after with some of these biological age clocks?

David Gobel: I did not do any of the clocks.

What I did do was all of the standard, plus extended, blood tests, all of the performance tests whole brain MRI and joint MRI, and CT scan thorax. So I have lot of data that will be before and after, but none of the clocks. The reason I didn’t do the clocks is because of the error bar. At the time that I was looking at them, the error bars were plus, or minus five to seven years. And so I did not feel that it was strong enough to spend the money because it’s expensive.

Laura Minquini: The best testament is how you actually look. And I know that in longevity discussions on clubhouse, we’ve said that if people can see the difference or feel it, it will be the biggest proof that this leading a longevity lifestyle or taking some of these therapies do work with that said we are almost at the top of the hour and I wanted to quickly reset the room.

Also open the room for questions and let everybody else know that we will be bringing them all up. We do hope that you have a bio and for you to be able to come up on stage. So we’ll be doing that momentarily. But again, we wanted to welcome everybody to this panel with the scientists reversing aging and without having to go into further introductions.

I will let Avi go to the next question while we open up the stage for the Q&A.

42:53 – Avi Roy: Thank you, Laura. And thank you everyone for answering the question. If anybody feels that they haven’t been able to answer something or something came up as in they thought about something just now feel free to answer while you’re answering the next question.

So the next question is a little bit interesting. This comes up all the time. I know many people here, like Aubrey, David Sinclair you have written books and put out the way you guys think and what you guys are thinking about the world of tomorrow. But many people ask about, and they try to get to this question.

So the question is, what are the two or three things – it doesn’t have to be two or three things if it’s just one – what are the two or three things that you intrinsically believe that it is inevitable in the future of longevity/aging/health within the next decade? So it’s a short timeframe I realized, but what is it that you pretty much base all your experiments?

You know your companies that you’re building, all of these things that you were thinking about, your research. And so what are those things, and what are the obstacles do you think that can impede that progress? And this is only over the next decade. Please jump in.

Aubrey de Grey: Yeah, let me jump in first, because I’m afraid I have to jump off the call in a few minutes at the top of the hour.

So actually the thing that I think is most inevitable over the next 10 years, since that timeframe you asked about, is a change of public attitudes with regard to what’s going to happen in the subsequent 10 or 20 years. At the moment, almost everybody in the world still believes that they’re probably going to live only a few years longer than their parents did.

And they’re going to stay healthy for only a few years longer than their parents did. And I’m convinced that there will be a tipping point where the results, and indeed the public statements of people like myself and David are going to change that. And when they do those states, those changes are going to happen very suddenly.

I believe there’s going to be a really sharp tipping point. When people like Oprah Winfrey get on board with this, that is going to introduce, there’s going to be going to herald a very turbulent few years while we figure out what to do with the general belief on most people’s path that they’re going to live healthily for a lot longer than their parents did.

This is something that I don’t think anybody’s really ready for, and whether it’s in governments or in the financial services sector or whatever. And I think that it’s very likely to happen within the next 10 years. I would say it’s quite likely to happen within the next five years.

David Sinclair: Yeah, Aubrey well said. I can feel it already in society. I think this clubhouse meeting here is evidence of that. We’re living through this really historical moment where, I don’t know if you’ve followed over in me for that long, but even just 10 years ago, and certainly 20 years ago, we were really on the fringe and people thought we were crazy.

And it was actually frankly, close to career ending to talk about age reversal. I think it was about seven years ago I first started using that, and it was outrageous at a talk at Stanford. So now it’s not mainstream, but it’s about to breakthrough. And it’s an exciting time. I just want to add what else will I see in 10 years?

I think it’ll be common to be monitored by your doctor. It’ll be common to take senolytic cocktails. It’ll be common to treat diseases with therapies that reverse aging. Whether it’s the eye or the whole body, I don’t know, but I’m certain there will be ways to reverse age. Not just by a few years and Greg, your work is amazing and awesome, thank you for that, but by a decade or two. And we’ve seen at least in animals now that the epigenetic age reset and the restoration division it goes on for a long time. This may be quote unquote, a permanent reset until you age out again, and then you can keep resetting the body. And we don’t know how many times you can reset the body yet. We know it works once, but I would bet that it works 10 or a hundred times. And then we’re really talking about a change in the way we can view our lifespan.

Greg Fahy: By the way, we’re very interested in that same question with respect to the thymus, David, if we regenerate the thymus, can we then regenerate it again and again. So if that’s something we look forward to finding out.

Liz Parrish: Oh, so I guess I’ll chime in here. I agree with that. I think that a lot of what you’re going to see is attitudes changing and I think that’s fantastic and that’s absolutely necessary. You’re going to see the slow drive of data that’s going to start to come through scientific papers, showing extended lifespans in model organisms, and then, soon in humans.

You’re going to hear more people talk about it, but of course, an obstacle is always, how difficult it is for small companies to get into clinical trials. So right now I’m doing my thesis for my MBA and it’s vastly on a new route of regulation not through the FDA, going around the FDA, but through the same departments of human and health services. In order to get people who are terminally ill access to better drugs. And so the right to try, doesn’t give access to the drugs that we’re talking about today. I call them best choice medicine, and that’s the drugs that perform better in early basic research than anything we have available on the market and those drugs exist, and that’s what everyone on this call is talking about. But these are still vastly experimental, but without human data, we can’t really get to them. So hopefully we’ll get the regulators to look at new routes that indemnify themselves from the difficult choices that they have to make and making decisions about new drugs.

People will see that they will see new options open for patients to take part in. They’ll see more data coming out and, what can block us is of course the enormous amount of money that it costs otherwise to get to even the regulatory service.

Millions and millions of dollars’ worth of animal data that again is not a very good predictor. And then the 2.6 billion estimate from Tufts university to actually get a drug approved. Let’s remove those roadblocks.

Avi Roy: Anybody else want to chime in about intrinsic knowing what, what the next decade looks like?

David Gobel: I can tell you what our provisional roadmap is, if you’d like?

Avi Roy: Yeah, please. That’ll definitely be based on your system that, on your things that you can believe, right?

David Gobel: Our vision is to make 90 the new 50, by 2030. We deliberately chose a falsifiable goal, 2030 that’s eight and a half years.

So we have to figure out where the holes are that would prevent that from happening. And so, in no particular order, we need to be able to deliver biological payloads to select body compartments far better than is available today. So delivery as a whole, we need reliable high quality bulk sell supplies. Right now there’s not nearly enough high quality cells available to purchase one of the biggest rate limiters for the competitors in the vascular tissue challenge competition was they just couldn’t get the cells in order to do their organoid constructs. So we need high, reliable bulk cell supplies.

Distribution. Who’s going to deliver these interventions? It’s going to be licensed practitioners. Do any of them know anything about what we’re doing in significant numbers? My experiences that physicians pretty much stopped reading papers the day they get out of the university, because they have no time they’re spending all their time dealing with the insurance companies and such.

And of course I’m speaking hyperbolically, I know there are exceptions and they are wonderful. So also trusted validation – do you know that the pill that you’re taking actually has any of the crud you’re actually trying to get inside of you? I have no idea if the stuff I’m taking is actually the stuff I think I’m taking.

What’s missing? Let’s see, the regulators need to accept patient trials in a dish because models that are based on animal models are awful. They’re not just not very good, they’re awful, and they’re awful in ways that people don’t even think of anymore. If you were to say is it okay to just take these animals, and torture them, and ruin them, and break them apart, and stick things in them? No, it’s not okay. It’s just what we have to do today.

We have to get away from that, it’s a moral imperative. Aside from patient trials are just much better. Vastly better in terms of speed and accuracy of coming up with interventions. Engineered functional organs, so we need to go to a next level for the vascular tissue challenge to scale it up to actual, clinically relevant, constructs like liver patches, and so forth.

Optimize nutrition biofeedback. Okay, you’re eating this leaf. Is it really good? Sure, it says organic, but is there anything in it that I need? And by the way, what do I need? And that’s based on our deep space food challenge with NASA. You should perhaps look that up ‘Deep space food challenge‘, is a wonderful challenge being put on by NASA and Methuselah.

Individuals need to own their own bio-data so that they can get prescriptions and diagnosis. This might go on to the blockchain, and then let’s see. One more thing.

There’s always one more thing. I think I’ve taken up too much time. Sorry.

Jean Hebert: I might add very briefly because I’m sure we want to get to questions that, and hopefully this is a safe prediction, that the enthusiasm for longevity research and the funding that goes along with that continues to increase in the next 10 years.

That’s all I wanted to set to add.

Joao Pedro de Magalhaes: Two quick points. I certainly think that in terms of longevity, as Jean was saying, yes, I think it’s going to increase, people are not going to get younger, we still have an aging population, so they will continue to be interested in developing interventions.

So I certainly see the developmental longevity & pharmacology longevity drugs as becoming a reality in the next 10 years. I’m a little less optimistic about rejuvenation technologies or reversing aging.

First, because we don’t really know how to do it in, even in animal models, we can manipulate aging, we can delay aging in animal models, including in mice, but we don’t know how to reverse aging. So I think there’s still a lot we have to figure out in that context. I think there’s some promising approaches; David Sinclair was talking about the Yamanaka factors, all three of the Yamanaka factors that they have used. But it’s still not very clear how you then turn that into a human therapy for instance.

So I would say the next 10 years, yes. I see a continued growth in longevity industry, longevity biotech, research on aging, developing the longevity drugs but not necessarily, unless there’s a big, massive discovery, not necessarily on reversing aging or rejuvenation technologies.

Laura Minquini: Thank you, Pedro. I want to give a chance to Alexandra and Greg to perhaps also answer this before we go into the Q&A. We’re very happy to have so many people interested in asking questions and wanting to chime in the conversation. Just wanted to move this along as you saw, a couple of our speakers had to leave.

So I want to make sure that we get to answer as many questions as possible, as some other of us speakers probably have to leave as well. But, Alexandra, Greg do you want to want to chime in?

Greg Fahy: I’ll let Alexandra go first.

Alexandra Stolzing: Okay. If you want to, I would hope that people would take more interest in their own the health and would become more empowered, and all these kinds of like positive signs that are coming from the trials that are currently running would kind of inspired them to really become invested in their own health, and try out more, and pay more attention to their health. So I would hope that this is a trend that carries on and becomes bigger.

Greg Fahy: And I just think that the example that we’re trying to set, which is to show that aging intervention can be done now begins to catch on as a concept, and as the evidence accumulates, I think it’ll become more and more obvious something significant is actually happening. Sergey young has recently bought into the idea of using repurposed drugs to advance the cause of aging intervention.

I think it’s a really good idea because the barriers to getting these things through FDA approval process are quite light. For example, with our therapy, we were able to show statistically significant improvements in kidney function in nine guys in a one-year period of time. So if that could be made into a yardstick for FDA approval, we should have a ridiculously easy time compared to people who are attempting to develop entirely new drug entities.

And by the way, there are ways that we can improve human growth hormone to make that into a separately approvable drug that we can essentially own ourselves as well. So that even though it’s a repurposed drug, it’s effectively a new drug. So this kind of paradigm, if this leads to early signs that you can actually do something meaningful on a clinical basis about aging, I’m not in 10 years or 20 years, but maybe in one or two or three years, then I do think the attitudes will begin to change in an optimistic direction. I’m already seeing lots of signs of this. I’m seeing increasing enthusiasm over the possibilities. So I do think that there is a sea change coming and it’s going to be boosted by many different advances that are all coming into aging from different directions.

But I think that we’re beginning to see signs of this happening already.

Laura Minquini: Thanks, Greg. We’re going to go now to our Q&A part of this discussion.

We would like to say a huge thank you to all of the panelists for giving us a portion of their busy schedules, and providing such an enlightening and thoroughly fascinating conversation. Our thanks also goes out to the hosts who