The Future of Aging with Aubrey de Grey
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Welcome back to the Health Longevity Secrets show with your host, Dr. Robert Lufkin. His book titled Lies I Taught in Medical School is a New York Times bestseller. See the show notes for a link to download a free chapter. And now please enjoy this week's episode as we speak about the future of aging with Dr. Aubrey de Grey.

We hope you can join us this week where Dr. Aubrey de Grey reveals why reversing aging may be easier than slowing it down in this mind-expanding conversation that challenges conventional wisdom about human longevity. The renowned biomedical gerontologist outlines his damage repair approach that's gaining mainstream scientific acceptance after initial skepticism.

At the LEV Foundation, Dr. DeGray is conducting a thousand mouse study, combining four different damage repair interventions in middle-aged mice. And he's aiming for a full year of life extension, which in mouse terms is about 30 years in human terms, which is far beyond the four months normally achieved.

Unlike conventional approaches that rely on dietary modifications, this ambitious project incorporates advanced cell and gene therapies that target multiple forms of age-related damage simultaneously. Now, looking forward, Dr. DeGray offers his characteristic probabilistic prediction, which is a 50-50 chance of reaching, quote, longevity escape velocity, unquote, within 12 to 15 years.

This would enable taking 60-year-olds and rejuvenating them enough that they would be biologically 60 again for another 20 years, during which time further advances would enable additional rejuvenation cycles, potentially creating open-ended healthy lifespans for many alive today.

This episode is brought to you by El Nutra, maker of the Prolonged Fasting Mimicking Diet. If you'd like to try it, use the link in the show notes for 20% off. What's the best imaging test to assess health and longevity? I used to think it was the CT coronary artery calcium score. Well, I don't anymore because now with the same x-ray exposure and time as a calcium score, I can get a complete metabolic heart scan.

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This scan is available anywhere in the U.S. without a doctor's prescription. See the attached link and use the code LufkinCT for $100 off. Join the health longevity medical imaging revolution today. And now, please enjoy this week's episode. Hey, Aubrey, thanks for coming on the show. Well, thank you for having me, Robert.

It's so great to talk with you as an expert in longevity, especially with all the early stage research you're doing. I love it. Well, maybe just start off. We're undergoing a revolution in longevity knowledge and things are moving faster than have ever occurred before in longevity. What are the most exciting things that you've seen maybe in the last five years you think that really surprised you?

Wow, I mean there are surprises coming along all the time and they're pretty much all good surprises I guess the single biggest surprise in the entire industry was the arrival of evolution in other words the commitment by the Saudi royal family to put ideally a billion dollars per year for 20 years into longevity research and development that

has taken a little longer than we were hoping to actually bear fruit. They're certainly not spending anywhere near a billion dollars a year yet, but they have put the right kind of groundwork together. They've certainly got an extremely appropriate person running the show, Mehmood Khan.

And they've had extremely good top management as well. People that I know who are, you know, I really trust to get things right. So that's definitely even though it hasn't really borne full fruit yet, it's definitely a huge thing. And it was a very big surprise.

Quick question on evolution, just excuse me for interrupting you, but in evolution, it seems to follow along several other big companies in that space or big projects with, you know, Calico initially with Google and then, you know, Altos with a number of funders, including Jeff Bezos and now evolution. How do these three companies differ and what are their, how are their approaches different? Yeah.

Right. So actually, yeah, I was going to go to that because, as you say, these companies are, if not as big as evolution in terms of dollars, they are within range. They were not quite such surprises to me because I was aware a long time earlier that both the Google twins, in the case of Calico and Bezos, had considerable interest in this space.

and indeed it was highly frustrating to me that they hadn't actually helped philanthropically at all but they're just the kinds of people who don't really believe in non-profits doing good work in technology I guess and

and eventually they decided to do something that was nominally for profit, though of course they don't actually need to make money out of these things. Calico, to be perfectly honest, has been an absolute disaster. It has been put together in a very inferior way such that it doesn't really have a pipeline. It doesn't really have any way to take proven concepts and turn them into products. It's got...

like the curiosity-driven basic science very well nailed down in terms of the quality of personnel. And it's also got the actual business end, the kind of Genentech Mark II run by obviously the person who used to run Genentech, but it doesn't have anything in the middle linking the two. And so it'll be complete luck if it ever does anything useful. It's an absolute tragedy.

Altos, I have considerably higher hopes for. Bezos started talking to me back in 2006 about aging. Again, never gave us any money, but...

but did eventually decide to put proper money into this area. The good news with Altos is that they hired a lot of the top people in the field, which means that no one school of thought is going to dominate what goes on there. You know, the whole way it's being done is a little curious. You know, Bezos never talks about it. It's kind of only kind of half-cultured.

announced that he is even the main funder. And they are not allowed to describe themselves as a longevity company. It's a little weird. But I do have faith that they're going to do good work.

Then there are, of course, other ones. So a lot of the people in crypto, the big hitters in crypto have been getting into this. And some of them have been helpful philanthropically. Vitalik Buterin is well known as one of the people who have given me and my various organizations quite a lot of money over the years. Brian Armstrong, who created Coinbase, has created a company again, New Limit, very heavily funded.

And then, of course, there's Retro, which is probably the single most promising of these companies because Sam Altman decided to throw proper money at this thing, a couple of hundred million, and he did it right. He actually found a proper longevity crusader to go and run the thing, Joe Betz-Lacroix, who's a great friend of mine, and I have very high hopes that Retro will achieve great things.

And the optimism for retro versus these other companies is based on the leadership of this individual, or is there some strategy they're using that's different or some particular approach to longevity that they're taking? It's mostly the leadership.

Essentially, Joe is the kind of person who actually understands the goal, thinks like an engineer, thinks like me. So he's going to get things right.

Yeah, that makes sense. And well, on this topic, before we can get back into the longevity things, but on this topic, you mentioned Vitalik Buterin, and we were talking off camera a little bit about your experience with,

down in Prospera, that community in Honduras, which just had a wonderful conference. I think you were at there. Maybe you could tell our audience a little bit about this and why you're so excited about it.

So this all started several months ago with the creation of a remarkable event in Montenegro called Zuzalu. And this was essentially conceived and bankrolled by Vitalik Vissarion. Essentially, he was able to bring together a couple of hundred people for a couple of months. I only attended one week of it. But, of course, quite a lot of people attended most of the event.

And the idea of it was to essentially explore whether something that could, something that was longer than a conference, but, you know, still had a couple of hundred people, could do things that no classical format could do. Essentially, if it could, you know,

be more effective at community building, at bringing ideas together, mutual education and so on. And it was very successful. So the whole idea has very much become a kind of a program to do such events all over the world in various places and in various ways.

And the second one, which is called Vitalia, happened. Well, it's happening right now. In fact, it started on, I think, January the 6th. And it normally was going to go until March the 1st. They've actually extended it by another month. I was there for the first month. And it's really going to make a difference.

The thing that distinguishes Vitalia from Zulu, the main thing, is that Vitalia is happening in Prospera. Prospera is a special economic zone in Honduras, not actually on the mainland. It's on an island called Roatan. So it's been set up to be, you know, to have everything that you might want in a special economic zone. It's very safe. It's like, you know, it's Western, really, in most ways. And...

In particular, what they wanted to do is to emphasize biomedical innovation. So they've set themselves up legally in such a way as to really maximize the incentives for clinics and companies to incorporate or relocate there and to get stuff done that they would not be able to do in more traditional jurisdiction.

in particular the regulatory structure, because they have very wide legal autonomy, not over criminal law or the military or anything, but they have basically everything else, they can put together their own regulatory structures. And they are showing very clearly that the safety that people need in the testing of new medical interventions

can be achieved without any compromises in a tiny fraction of the time that it takes in the US, for example. And so, of course, this is rather attractive to rather a lot of people. I cannot speak too highly of these people. They are very, very competent. They have enormous energy. There's a lot of representation from the younger generation, shall we say.

And, you know, they're getting things right. So I will go so far as to say that I think it's quite likely that within even a couple of years from now, Prospera will be the global hub for medical tourism. And it won't just be because of these events like Vitalia, but that's certainly giving the thing, you know, its original impetus.

And the more this happens, the better, of course. So there are other similar events happening around the world that are planned for later this year, for next year. Actually, Vitalik himself is kind of taking a bit of a back seat. I understand that he did not provide financing for Vitalia and he didn't turn up either, whereas he very much did that for Zuzulu.

Well, plenty of other luminaries did turn up, so I wasn't the only one. There's a huge emphasis on the concept of network states, so decentralized, legally autonomous entities. And the guru of that whole field, Balaji Srinivasan, also came along in person.

Various other people have got involved, people who will raise the credibility and reputation of this whole enterprise. So I believe it's got what it needs to make a huge difference. And so Vitalia then will be an ongoing organization there. We'll continue on. It's just not a one-time conference, but it's sort of long-term. So Prospera is the name of the special economic zone. That is absolutely perfect.

The TARIA, I think, is a kind of flexible concept. It was originally supposed to be this two-month thing ending on March 1st. They've already extended it. The companies, the entities that are...

who either coming out of Vittalia or are being attracted to Prospera by Vittalia, these things will obviously in many cases be permanent as well. So it's kind of a little bit of a gray area whether you call Vittalia permanent or not.

I see. Yeah. And well, you mentioned several other conferences, upcoming conferences around the world that you're excited about. Could you share some of those? Well, so let's not call them conferences. Because, I mean, it's a bit difficult to call something that's two months long a conference. What they're actually calling them is pop-up cities.

But yeah, I mean, there are ones planned elsewhere in the world. There's one I know being planned in Africa, I think in Zanzibar. There's a couple of ideas for South America. Uruguay apparently has particularly friendly legislation when it comes to special economic zones. So there's a bunch of thought going on there. I'm not the expert there. You should really talk to the people who are involved.

who are running this show in order to understand that. Yeah, yeah, we'll get some of them on here. But yeah, it's such an exciting area. So it sounds like you see development of biotech projects

In this case, sort of without the bureaucratic over scrutiny or the weight of the FDA on it that slows things down and many people think unnecessary in many cases. And I think I want to emphasize that this is really the most important thing is in the near term, in a small number of years, because...

To the extent that this succeeds, it will create a huge amount of FOMO. There will be enormous incentives for traditional jurisdictions, whether the US or elsewhere, to actually get on with modernizing their regulatory structures so as to compete with structures that are not doing this.

That is already happening to a small extent. So I do want to highlight something that happened last year in Montana, where the state legislature passed a law that very meaningfully extends the concept of right to try.

So I'm sure you know that at a federal level, there's this law that's saying if you're terminally ill and you've been through everything that's been approved, you can access things that have not been approved. You don't get reimbursed for it. You don't get insurance, but it's legal as long as someone has to prescribe it, of course.

What they've done in Montana last year is they've said that if a treatment has got through phase one, so the safety part, and of course, you know, hundreds of 98% of treatments that get through phase one never get to phase three, right? And the ones that do don't get there for a very long time.

This is FDA phase one, just for our audience so they know. Yeah. If something's got through phase one, then you can access it in Montana now, even if you're not terminally ill or ill at all. Again, you don't get insurance, it doesn't have to be prescribed, but it's a vast change. It means that...

you know, we've got access to very many, I mean, huge numbers of treatments that otherwise would not be available.

And, of course, the goal is to spread FOMO across the US and get other states to adopt the same legislation. The state senator, Ken Bogner, who spearheaded this in Montana, is now running for Congress, and obviously that will be a big part of his platform. We were somewhat involved in this. We seed-funded an organisation called A4LI, the American...

the Alliance for Longevity Initiatives, which drafted the legislation and worked closely with Ken to make all of this happen. So I've been following this very closely. But yeah, coming back to the ProHUB cities, I honestly don't believe that that kind of initiative will move nearly fast enough without the incentive from elsewhere in the world to, you know, to compete.

Yeah, wow, so many things happening. That's wonderful about Montana, getting access to these early-stage drugs that have been proven to be safe, but they haven't made it all the way through the system. Now, I guess all we need to do is get the definition of terminal illness modified to include

aging and longevity, which is the terminal illness we all have. Let's talk about that for a moment because terminology is always an enormous barrier to progress. Yeah, language matters. So that may actually be the way to go. The problem that I've encountered throughout the time that I've been engaged in public outreach in this space, and so more than 20 years now,

is fundamentally that the public are deeply suspicious of preventative medicine in general. They are suspicious of new medicines with some degree of justifications. New medicines sometimes don't work.

But in particular, for preventative medicine, you know, the person's not yet sick and they are therefore scared that some new medicine might make them sick and they don't see any real, you know, risk-benefit ratio attraction there. So educating the public that actually prevention is a rather good thing is, you know, really important and really, really, really difficult.

And framing of that, perhaps as simply saying, you're already sick, you've already got aging, is something that may make a difference.

I'm definitely not a natural marketer. You know, I feel, you know, the way I put things out there, you know, to the world, it resonates with some audiences, but not with others. So I'm not the person to trust in terms of my judgment on that. But I do certainly think that it's an option and it's a vital thing to achieve to get the public more comfortable with preventative medicine for the chronic conditions of late life.

Of course, my work, this work on damage repair that I focused on for all these years, is kind of treatment or prevention, depending on how you look at it. It's kind of the sweet spot between the two because it's designed to be applied to people who are not yet going downhill functionally, but equally it does actually turn back the clock in terms of removing damage and putting the body back into a state that approximates how it was at a younger age.

And perhaps that can also be leveraged, you know, rhetorically. But again, you know, it takes marketers to figure that out. Yeah. Well, maybe you could talk a little bit about your work that you're doing, some of these interesting projects. We talked a little bit, again, before off camera, but I'm sure the audience would love to hear about that. Yeah, sure. So, yeah, of course. So, yeah.

So to flesh out what I said a moment ago a little bit, my work for the past 20 or more years has been focused on implementing a really dramatic paradigm shift that I introduced in the year 2000.

which was the idea that if we want to actually treat ageing, then it may be easier to reverse it than to slow it down. This sounds very counterintuitive, and it sure as hell was very counterintuitive to my colleagues. It took me several years to persuade anybody that I was not talking complete nonsense.

But it's now a very widely accepted concept. And essentially, it comes down to the fact that if you want to slow aging down, essentially what you're doing is you're thinking of the body as a machine, you're making it run more cleanly. And that's really hard. You have to really understand how it runs in order to do that without having unintended consequences.

And we just don't understand the body anywhere near well enough to be able to do that significantly. So people have basically got nowhere with that.

But reversing aging is more a case of preventative maintenance. It's a case of simply getting rid of the damage that the body does to itself throughout life in the course of its normal operation and restoring the structure and composition of the body at the molecular and cellular level to something like how it was at a younger age, like in young adulthood.

And you can do that in principle without understanding anything about how the body created the damage in the first place. And yet you achieve the goal of ensuring that the damage does not become abundant enough to exceed what the body is set up to tolerate and thus to make us sick and to make us suffer the chronic conditions of late life. So as I say, this concept has now been broadly embraced by the field, but you've still got to implement it. And implementing it

comes fundamentally into two stages. And the reason it does is because it's a divide and conquer approach. Obviously, the body damages itself in many, many, many different ways. First step to understand how to actually get one's head around that and one's arms around it is to classify those many different types of damage into a manageable number of categories. And that's what I did back in 2000. I defined seven categories.

And then to align each of those categories with a generic approach to actually doing the damage repair. Okay, so that's what I did. And some of those damage categories are much easier to address than others. So in my previous organization, Sense Research Foundation, we focused on the most difficult ones, the ones that other people were neglecting simply because other people had different incentive structures. They needed publications every 10 minutes. They needed, you know, to satisfy shareholders or whatever.

We, being entirely funded by philanthropy, were able to avoid those constraints. And that's why we were able to work on really difficult things.

And that was very successful. We progressed a number of projects over the years to the point where we could spin them out of startup companies. We did that half a dozen times. So that's all great. But it's only stage one because once you have implemented the various methods to repair this or that type of damage, and once you've got them reasonably working, at least in mice,

you've still got to put them all together because each one individually is not going to make much of a difference to how long someone stays healthy. So the putting them together part is something that's only really become a thing in the past few years because it's only in the past few years that there's been enough progress on the individual things, even in mice, to have something to put together. And so now my new organization, LEV Foundation, that's what we're doing. As soon as we kicked off the new foundation,

we kicked off our first really big project, a thousand mice being given four different treatments in various subsets of those four, treatments that address different types of damage in aging and seeing how well they synergize. So that project began a year ago.

A key point to recognize is that we don't start when the mice are young. We start when they're already in middle age. So typical mice, healthy, normal, non-mutant mice, they typically live about two and a half years. And so we start when they're already one and a half years old. So they've got one year to go.

Historically, the best that people have ever been able to achieve by doing anything to my starting when they're already one and a half years old is about four months of extension of subsequent life. And of course, the extra months are healthy months, which is good. We want that. But four is not very many. So we want to treble that. We want to get an entire year of extension of healthy life.

in terms of both the average lifespan and the maximum.

And we don't know whether we're going to be able to achieve that with the current experiment, but we've got plenty of other interventions and combinations of interventions lined up to test in this same way. And the only thing that's holding us back is funding. These experiments are very expensive. They are, well, the first one cost more than $3.5 million, and that's what each of them is going to cost.

but in terms of, you know, information gains per dollar, we believe I'm very confident. I'm very sure that this is the most, you know, um, um, value for money experiment that's being done in the entire field right now. So anyone who feels like helping or wants to know more about this, you know, look at our website. I'm sure you'll put it in the show notes, avf.org. Uh, there's a link at the top to the next study. Um, and of course I'm always available. Um,

by email and by Zoom or whatever to discuss anything like this with anyone who wants to help. - Yeah, that's so exciting. I mean, it's sort of like the interventions testing program

With mice, except you've expanded it to more freedom of things you can test. And you're starting at the older age, which is a much more realistic model for what a human interaction would be, intervention would be. The intervention testing program has been going on for about 15 years now. And I don't want to disparage it. It's definitely done a lot.

But yes, first of all, most of the interventions that they test, they start early in life. In fact, the reason that rapamycin is such a big deal these days, it all started with the interventions testing program accidentally starting their study rather late in life because they had real difficulty formulating the chow.

So that's one problem, that most of their interventions start early. Second one is that, by and large, they're testing interventions individually. Again, they do sometimes combine things, but not often. But the biggest thing, the biggest limitation for the ITP is that they only do orally available things. They only put stuff in the chat.

So that completely excludes cell therapies and gene therapies, which we are completely sure are going to be absolutely unavoidable if we want to get big results. So we are taking that on. We are biting that bullet. And that's a large part of why the experiments are expensive, but it's also absolutely essential.

Yeah. Yeah. Um, or back to, back to language, just a couple of things. I want to be respectful of your time here, but just a couple of last things talking about language, uh, Misha Blaglosconi and Leonard Hayflick have this idea of, uh,

you know they they they propose an idea that aging is due to uh damage cell damage and wear down but longevity is due to hyperfunction in other words with you know mtor and those sort of things is that all semantics or or what what's your take on that well so

Calling one of these things aging and the other one longevity is unhelpful, I think. It kind of already obfuscates things because these words have already got so much baggage from other causes.

But Michel Blagoscoloni's concept of hyperfunction is absolutely fine. It's completely valid, and it's not actually new either. It's really just the kind of modern expression, articulation, of something that was first put forward in the 1950s called antagonistic pleiotropy. Essentially, it just says that...

In the same way that we don't have genes that would be useful late in life because evolution doesn't care about old individuals because they've already passed on their genetic information. Similarly, we don't develop genes that turn off other genes late in life unless that's also useful early in life.

And so some genes will continue to do things that used to be good early in life and become bad. And various examples of this have been, concrete examples have been researched, especially in nematode worms. There's things that go on that are very overt in that regard. But it's a reasonable concept as applied to any species.

The only real question is, how much of a contribution does that kind of thing make to ageing? At this point, we cannot reasonably argue that it contributes all that much.

But of course, again, it depends on your definition. So some people would say, for example, that cancer is an example, that all of cancer is a result of antagonistic pleiotropy because essentially there's a trade-off between how well you

regenerate tissues and how close to the wire you are in terms of letting cells go AWOL, so to speak. Like, let's just look at telomerase. You know, telomerase is a gene that if you absolutely blitz it and you do not have any expression and you can't turn it on, then, you know, it's very difficult for cancers in large animals like humans to grow large enough to kill you.

But the fact is, unfortunately, we need a trace of telomerase in our regularly renewing tissues, like the blood or the gut lining, for example. And so it's not quite turned off. And that means that it can be epigenetically reactivated to an extent that will support cancer. And that's why 90% of human cancers have telomerase turned on at high levels.

Things like that. So there's trade-offs all over evolution, and some of these trade-offs evolution has taken the trouble to optimize, and some of them it hasn't. So the concept of hyperfunction is fine, but oversimplifying the language with which it is described is a bad idea.

The, you, you've talked about so many exciting things that are coming down the, down the road in longevity and the future. Maybe we'll just end up right now. We, you know,

what do we do today, like right now with what's available? Is it lifestyle? Is it going to be supplements? Is it rapamycin and A-carbos? Is it plasmapheresis? What should we be doing now for our longevity today? Yeah, well, I have to be honest and say that my answer to that question has not changed over the years, and it still is. Write me a large check.

At the end of the day, what matters is how much we can hasten the arrival of things that don't yet exist.

things that do already exist, you know, there really isn't much. One thing that we always have to remember is that nearly everything that works well in laboratory organisms is certain not to work well in humans simply because it relies on emulating the metabolic response to calorie restriction. The

You know, one thing that evolution has optimized is the metabolic response to famine.

And, you know, it works pretty well to adjust metabolic priorities away from reproduction and in favor of maintenance so as to improve one's chances of outlasting the famine so that one can have offspring that won't just immediately die before having their own offspring on account of starving. Right.

And that will make perfectly good evolutionary sense, but unfortunately, if you look at that logic even a little bit, you can see that long-lived species are not going to benefit very much, because long famines don't happen very often. And something has to happen reasonably often in order for evolution to care about it. So that means, yeah, that completely explains the very clear observation that's been around for 20 years at least, that

there is this inverse correlation between how long a species lifespan is and how much benefit it gets from calorie restriction. You can multiply the lifespan of a nematode worm by five by doing the right kind of little tricks to it. Of course, I'm not talking about calorie restriction itself on its own. I'm talking also about genetic and pharmacological tricks to trick the organism into thinking it's on calorie restriction.

And that's what nearly everything we have today, rapamycin, metformin, resveratrol, you know, that's what these things do in different ways. But still, that's what they do. So, yeah, I don't really expect to see anything significant in terms of extension of healthy lifespan in humans until we are ready for prime time with proper damage repair in the form of cell therapies and gene therapies of the sort that we're working on.

What's the horizon timeframe for that, do you think? How long do we have to wait? Well, people have been asking me that question for a while. And yeah, I mean, I do not shy away from giving timeframe predictions, but I always make sure to emphasize that they are probabilistic. So I say we have a 50-50 chance of getting to what I've called longevity escape velocity within 12 to 15 years from now, so the late 2030s.

And that's a point where we can take people who are, let's say, 60, biologically 60, average 60-year-olds, and rejuvenate them, not completely, but well enough that they won't be biologically 60 again for another 20 years or so.

during which time people like myself will have improved the therapies so that we can rejuvenate the same people so they won't be biologically sick for a third time until they're 100 or 120 or whatever. This is what we call longevity escape velocity and you have to get those first 20 years in order to activate this kind of positive feedback loop, this kind of thing.

You know, the term escape velocity is actually quite a good analogy with gravitational escape velocity. So, yeah, 12 to 15 years. But there's at least a 10% chance that we won't get there for 100 years because of any, you know, unanticipated obstacles that we may encounter. So I always emphasize the probabilities.

Well, that's such an exciting idea. And thanks so much, Aubrey, for taking the time and spending with us today. You mentioned your website. Maybe you could mention it again and how people can follow you on social media.

Absolutely. Please go to levf.org. L for longevity, E for escape, V for velocity, F for foundation. Everything is linked from there, including the conference. We run an annual conference. Of course, conferences have been a very big part of my work over the years in community building, and they still are. So our conference series now happens in Dublin in Ireland, and the next one is in mid-June, June the 13th to 16th.

They are fantastic events scientifically and socially. And so I encourage everyone to go. The link to the conference website is right at the top of the LEV Foundation website homepage. And also there is a link to our next study that we want to do that I was talking about earlier to be a sequel to the study we're currently doing with a thousand mice. We want to do another one.

And of course everything else about activities is there. You can email me at [email protected]. You can find me on social media, on Twitter @AubreyDeGray, you know, everywhere you would expect. Great. Well, thanks so much for spending time with us today, Aubrey. And thanks also for the great work that you do. Well, thank you for having me and I look forward to next time.

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