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The Need for Unity and Stability in Transhumanism – Article by Arin Vahanian

The Need for Unity and Stability in Transhumanism – Article by Arin Vahanian

 

Arin Vahanian


Although Transhumanism is heavily inspired by (and also inspires) advancements in science and technology, I believe the movement could also benefit from implementing cultural aspects; in particular, those from China.

This became very clear to me not just after living in China, but also after reading the works of Dr. Martin Jacques, British professor and journalist, who is, in my mind, one of the most knowledgeable Westerners when it comes to Chinese culture and history.

Specifically, in his writings and public appearances, Dr. Jacques has elucidated various aspects of Chinese culture, two of which I think are important for Transhumanism to consider: unity and stability. I shall cover each one briefly here, and explain how our movement would benefit.

Although the Transhumanist movement is rather decentralized, and I believe in keeping it this way, we most definitely need unity, especially in regard to our values and objectives. To this end, the U.S. Transhumanist Party has published its values on its Web site, which include but are not limited to: eradicating disease; the cultivation of science, technology, and reason; support of all emerging technologies that improve the human condition; life extension; reversing aging; tolerance and inclusivity of all individuals, and so forth. I believe every Transhumanist would support these values, all of which are noble, and all of which would most certainly contribute to having a better, more prosperous, and safer world.

Any organization, family, company, group, team, or political party, for that matter, needs unity in order to stay together and fulfill its goals and aspirations. Conversely, lack of unity may lead to chaos, discordance, and dysfunction. According to Dr. Jacques, the primary political goal for the Chinese is unity. Indeed, there would have been no way for Mandarin to become the national language, nor any way for the dizzying progress (whether it is technological, societal, or economic) we have seen in the country to have occurred, without unity. Please note that I am not advocating for a change in the political process anywhere else, nor am I suggesting that other countries adopt the same political or economic system as China. I am simply stating that being unified in our goals and values is incredibly important if we wish to fulfill these goals and proliferate our values.

Just as the Chinese look at themselves as Chinese, so we must look at ourselves as Transhumanists. However, there is one major difference; while not everyone can be Chinese, anyone can be Transhumanist. Our movement is inclusive to all individuals, regardless of race, gender, class, religion, and sexual preference. Therefore, I believe that we can be unified while also being open, tolerant, and accepting of all humans.

This leads me to my next point, which is stability. There is no question that in China, as well as other Asian countries, stability is paramount. After all, an unstable society cannot work together to fulfill its objectives and protect its values. Fortunately, we have stability in the Transhumanist movement in the areas of political leadership (Zoltan Istvan, Gennady Stolyarov II), life extension (Max More, Keith Comito), aging (Aubrey de Grey), and more. What’s fascinating is that the movement is so diverse and broad, and the areas for improvement on Earth so plentiful, that we have had individuals naturally dedicate themselves to causes they deemed worthy. This has contributed to stability in the sense that people are working on what they are passionate about, and these same people have, as a result, provided stable leadership in these areas. We must ensure that this stability continues, and that we help advance the causes we believe in by promoting them on social media and mass media. We must also support those who are bravely and selflessly dedicating their lives to helping humanity move forward. All of these actions will contribute to further stabilizing the movement and what it stands for.

Additionally, we must maintain stability in our relationships with each other, as well as the messages that we communicate to others. No matter how small or large a role we each take on, our mandate as Transhumanists is to push for reforms that will improve the human condition for as many people as possible, with as much beneficial impact as possible. In doing so, we must communicate our message that science, technology, and rational discourse should be used for efforts such as curing disease, increasing human longevity, alleviating poverty, and battling climate change.

While we are completely opposed to the proliferation of nuclear weapons, we are completely open to tolerance and inclusivity of individuals, and offer assistance to those who may have been shunned by the system, either due to disability or the desire to challenge society so that we may be better humans. We are an organization that values and promotes pacifism, and by doing so, we are creating a more stable society, and world.

So my call to action today is this. Rather than argue whether a certain economic system is better than another for Transhumanism, we should focus on our values and goals, thereby fulfilling our mission, and be supportive of whichever economic system best helps get that done, whichever country we happen to live in. Different economic systems work in different countries, and we should not be dogmatic, but rather, flexible and solution-oriented.

Additionally, rather than debate one another, we must instead discuss and cooperate, again, with the intent of pushing forward our goals. Debating takes valuable time and resources away from achieving our goals, and the time that is spent on needless arguments could be spent on finding solutions to challenges that threaten humanity. While it is perfectly acceptable and in fact, desirable, to have differences of opinion, we should use these differences to collaborate and help develop solutions to the problems we humans face. We are finally getting more traction in social media, mass media, and in various communities and countries all over the world, and so we should take advantage of these trends to further spread our messages of peace, increased health and longevity, and technological innovation that will benefit humanity.

One of the challenges the Transhumanism movement currently faces is an inaccurate and unfair perception that it is a niche movement, unable to appeal to most people, and the product of wealthy technophiles in Silicon Valley. However, nothing could be further from the truth. Among our ranks are people of all nationalities, social statuses, races, genders, and religions, and we are the only movement that supports morphological freedom. Further, we are dedicated to goals such as alleviating poverty, curing disease, eliminating nuclear weapons, spreading peace, and using science and technology to make life better for all humans, not just a privileged few. Surely these are values that most, if not all humans, could stand behind. Based on this, it is quite clear that Transhumanism is most certainly not a niche movement, and that it is one of the most progressive and inclusive movements the world has ever seen.

Therefore, the best way we can promote our messages and fulfill our objectives is by being unified in our purpose, mission, and values, and be stable in our leadership, approach, and relationships. Let’s not do our detractors’ work for them by being splintered and divided, nor become detractors ourselves. Let us coalesce for the betterment of humanity, and turn our detractors into friends, supporters, and partners. Indeed, the future of the world, and that of humanity, depends on it.

Arin Vahanian is Director of Marketing for the U.S. Transhumanist Party.

Interview with Dr. Aubrey de Grey by Yuri Deigin

Interview with Dr. Aubrey de Grey by Yuri Deigin

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Yuri Deigin
Aubrey de Grey


Editor’s Note: The U.S. Transhumanist Party is pleased to publish this in-depth interview by Yuri Deigin of Dr. Aubrey de Grey, the U.S. Transhumanist Party’s Anti-Aging Advisor. Herein Dr. de Grey offers original, in-depth insights regarding the current state of research and public opinion regarding the pursuit of advances in rejuvenation biotechnology that will hopefully achieve significant life extension, one of the U.S. Transhumanist Party’s Core Ideals, within our lifetimes.  This interview was originally published in the Russian language here. The English-language version was first published by one of the U.S. Transhumanist Party’s Allied Organizations, the Life Extension Advocacy Foundation (LEAF), here

~ Gennady Stolyarov II, Chairman, United States Transhumanist Party, July 29, 2018

Note from the Life Extension Advocacy Foundation (LEAF): Today we have an interview with Dr. Aubrey de Grey from the SENS Research Foundation. This interview conducted by Yuri Deigin, CEO at Youthereum Genetics, was originally published in Russian language and he has kindly translated it into English so our audience can enjoy it, too.


Yuri: Aubrey, thank you very much for agreeing to this interview. Why don’t we dive right in? I am sure everybody asks you this: how and when did you become interested in aging, and when did you decide to make it your life’s mission to defeat it?

Aubrey de Grey: I became interested in aging and decided to work on it in my late 20s, so, in the early 1990s. The reason I became interested was because that was when I discovered that other biologists were almost all not interested in it. They did not think that aging was a particularly important or interesting question. I had always assumed, throughout my whole life, that aging was obviously the world’s most important problem. I thought that people who understood biology would be working on it really hard. Then, I discovered that wasn’t true and that hardly any biologists were working on it. The ones that were weren’t doing it very well, not very productively as far as I could see. I thought I’d better have a go myself, so I switched fields from my previous research area, which was artificial intelligence.

Yuri: By the way, do you think there are disproportionately many people from computer science in aging research these days?

Aubrey de Grey: There are a lot, and there are lots of people who are supporting it. Most of our supporters are, in one way or another, people from computer science or from mathematics, engineering, or physics. I think the reason why that has happened is actually very similar to the reason why I was able to make an important contribution to this field.

I think that people with that kind of background, that kind of training, find it much easier to understand how we should be thinking about aging: as an engineering problem. First of all, we must recognize that it is a problem, and then we must recognize that it is a problem that we could solve with technology. This is something that most people find very alien, very difficult to understand, but engineers seem to get it more easily.

Yuri: So do you think that people who don’t have such a background, this way of thinking, have a chance of understanding the importance of this problem, or are they better off letting people with an engineering mindset figure it out?

Aubrey de Grey: Well, of course, there is always an overlap. The reason I spend so much time doing interviews and running around the world giving talks is precisely in order to help people, for whom this is not obvious, to think about these things. For any new idea or any new way of thinking, there are always people who understand it first and who then communicate that knowledge to other people.

Yuri: Right. And you have been running around giving talks for a very long time, as I understand. It’s been, what, twenty years?

Aubrey de Grey: Well, at least 15 years that I’ve been doing a lot of it.

Yuri: So between the time in your twenties, when you realized that aging is not something that’s being adequately covered by biologists, and the time when you decided to have a go at it yourself, how many years have passed? And can you give a bit more background on when you founded SENS and what SENS is?

Aubrey de Grey: Sure! The year in which I switched fields properly is probably 1995. For the next five years, I was basically just learning. I was going to all the conferences, getting to know the right people, leaders in the field. Learning a lot of what was known and doing a huge amount of reading, of course. The big breakthrough came in the summer of 2000 when I realized that comprehensive damage repair was a much more promising option then what people had been doing before. Since then, it has been a matter of persuading people of that.

There were a few years when I was just ignored and people thought I was crazy and didn’t think I made any sense. Then, gradually, people realized that what I was saying was not necessarily crazy. Some people found it threatening, so in the mid-2000s, I had a fair amount of battles to fight within academia. That’s normal; that’s what happens with any radical new idea that is actually right, so that happened for a while. This decade, it’s been rather easier. We founded the SENS Foundation; we’ve started getting enough donations into the SENS Foundation to be able to do our own research, both within our own facilities as well as funding research at universities and institutes. Gradually, this research had moved far along enough that we could publish initial results. Over the past two or three years, we’ve been able to spin off a bunch of companies that we have transferred technology to so that they can actually attract money from investors.

There are, of course, an awful lot of people out there who believe in what we are doing, but they fundamentally don’t like charities; they don’t like to give money away. They have been waiting for the point when these projects move far enough ahead that they are investable, and that’s resulting in much more money flowing into these areas.

Yuri: This is a good point you bring up – that a lot of wealthy people for some reason aren’t prepared to spend money on fundamental research on aging but somehow desire a financial return on their investments in this field. Do you know why that is? Why can’t they realize that in their position, it is much more rational to try to convert their wealth into something much more valuable that they cannot yet ever get back, which is years of healthy life. Why do they try to also make money on this research?

Aubrey de Grey: Well, it’s not really a rational decision, and it’s different for every individual, whether it’s for that reason or any other. Let me first say that it actually seems less of a problem in Russia. Our single biggest donor at the moment is Vitalik Buterin, the guy who created Ethereum, who is a Canadian of Russian heritage. Another major donor of ours is a guy named Michael Antonov, one of the co-founders of Oculus. I think maybe Russians have less of a problem with this. However, in general, the kind of people who have a lot of money and who are also visionary enough and understand technology enough, they tend to be the kind of people who made their money by doing certain things; they got it through the capitalist system. So, those kinds of people are inherently biased in favor of that system and against philanthropy. Then, of course, there are many other reasons. There are some people who won’t give us money because they don’t think it’s a good idea to defeat aging. There are plenty of people who want to give us money, but their wives think it’s crazy. I am not kidding! There are at least a couple of our major verbal supporters who I know for a fact that that’s why they are not giving us significant amounts of money. Another reason, I think, is that some people just have overly big egos, so they think they can do better than us even when they can’t.

Yuri: Let me probe you a little bit more on this. You brought up wealthy Russians and people who think they can have a go at aging themselves. Would Sergey Brin qualify as one of those people who decided they know better and founded their own company, Calico, for precisely this reason?

Aubrey de Grey: Yeah, I had a funny feeling you might ask me about that. I have a very low opinion of Calico. The fundamental reason for this is because of Larry and Sergey. In fairness to Sergey, my understanding is that Calico is mainly a Larry project, or at least more so than a Sergey project. Of course, they are both on the Board of Directors, and they both share the responsibility. At the end of the day, Calico is a catastrophe, and it’s their fault. They just created it wrongly.

They’ve known me for fifteen years; they could easily have told me, “Listen. We don’t like charity. We want to create a company, and we want you to run it,” and I would’ve said “No problem!” and they knew that. Instead, they decided to be more traditional about this. I don’t know why. Maybe they don’t like people who have beards.

The fact is that they made an absolute catastrophe of it. They started out reasonably sensibly by hiring Art Levinson, the world’s best biotech CEO, but what they didn’t do was tell him what to do next. They gave him a job to cure aging, and he doesn’t have the slightest idea how to cure aging, and he knows that he doesn’t have the slightest idea. So, he hired someone who he thought would have an idea how to do it and made him Chief Science Officer. Unfortunately, he didn’t know how to make that decision either, so he hired completely the wrong person. He hired a completely inveterate basic scientist, David Botstein, who is a fantastic scientist but who doesn’t understand technology. In fact, he went on record saying that he doesn’t have a translational bone in his body. You don’t get that sort of person to run an outfit that’s supposed to be solving a technological problem. Sure enough, they are doing fantastic research that will understand aging better and better as time goes on over the next century, but they will never, ever, if they follow their current strategy, actually make any kind of difference in how long people can stay healthy and, therefore, how long they can stay alive.

Yuri: Why do so few people have a sense of urgency that we need to do everything possible to combat aging within our lifetimes and not centuries to follow?

Aubrey de Grey: There are two answers to that. The David Botstein answer, the Calico answer, is that they just don’t understand the idea of knowing enough. People who work on basic science understand how to find things out, but that’s all they understand. For them, the best questions to work on are the questions whose answers will simply create new questions. Their purpose in life is to create new questions rather than to use the answers for a humanitarian benefit. They don’t object to humanitarian benefit, but they regard it as not their problem. You can’t change that. Botstein is a fantastic scientist, but he’s in the wrong job.

The other part of your question, why people, in general, do not regard aging with a sense of urgency, has a different answer. People weigh up the desirability and the feasibility. Remember that everyone has been brought up to believe that aging is inevitable, I mean completely inevitable in the sense that stopping it would be like creating perpetual motion. If the probability of doing something about this thing is zero, then the desirability doesn’t matter anymore. So, under that assumption, we really ought to put it out of our minds and get on with our miserably short lives. That’s all we can do.

Yuri: So it’s a case of learned helplessness?

Aubrey de Grey: Yes, exactly, it is learned helplessness, and it’s a perfectly reasonable, rational thing to be thinking until a plan comes along that can actually solve the problem: a plan that demonstrates that we actually might be within striking distance of genuinely solving the problem. That only happened quite recently. Of course, I have a huge mountain to climb to persuade people that we have crossed the boundary from this being just a recreational, exploratory field to it being a technological, translational field.

Yuri: Have you had success in the past fifteen years that you’ve been climbing this mountain; have you seen that the public’s perception has greatly improved?

Aubrey de Grey: Absolutely. Things have got hugely easier. I mean, there is a huge amount of the mountain still to climb, but we have climbed a hell of a lot of it. Just the nature of a conversation, the kinds of people who want to hear about this. The way in which credentialed scientists with reputations that they need to protect are willing to embrace this. We could not conceivably have created the scientific advisory board that we have now fifteen or even ten years ago. There are thirty people there who are all world-leading luminaries in their fields, and they are all signed up very explicitly to the ideas that comprehensive damage repair is a thing and that it actually has a good chance of genuinely defeating aging. So, I’ve won the scientific argument.

People are even reinventing the whole idea of comprehensive damage repair and pretending it’s a new idea. Five years ago, there was a paper called “The Hallmarks of Aging” published by five very senior professors in Europe. That paper is saying pretty much exactly what I said eleven years before it. The key difference is that unlike my work, this work is being noticed. In fact, it’s been more than noticed. It’s become the definition of what’s useful work to do. This one paper that was only published 5 years ago has been cited more than 2,000 times already. There’s no question that it’s going to be, by far, the most highly cited paper in the whole of the biology of aging this decade, and it has the same ideas that I put forward the previous decade. So that’s fantastic. I’d like to have more credit, but I really don’t care about that; what I care about is that the idea is now in the mainstream.

Yuri: You mentioned your plan for comprehensive damage repair; could you elaborate a little bit more on what the plan actually is?

Aubrey de Grey: Sure. The idea is to emulate what a mechanic would do to maintain a car. We know that this works; there are cars over a hundred years old that are still running and are doing so just as well as when they were built. We know that they are not doing that because they were designed to last that long; they were probably designed to last only ten years. They’ve vastly exceeded their warranty period, and they’ve done so because of comprehensive damage repair.

The only reason that we can’t do this to the human body already is that the human body has more complexity and more types of damage. However, it’s a manageable amount of complexity. In particular, the big thing that led me through to this route was when I realized back in the year 2000 that we could classify all of the types of damage that the body accumulates into seven major categories, for each of which there’s a generic approach to fixing it.

For example, one of the categories is cell loss, which is when cells are dying and not being automatically replaced by the division of other cells. The repair, of course, is stem cell therapy. We simply put cells into the body that have been pre-programmed into a state where they know what to do to divide and transform themselves into replacements for the cells that the body is not replacing on its own. That’s just one of the seven types of damage that I enumerated, and, of course, that direction is very well advanced. We have hardly ever done any work in stem cells because we didn’t need to; other people are doing all of the work that’s necessary.

The other six categories are more neglected; they are in an earlier stage. That’s why we created the SENS Foundation to push them forward. We’ve been very successful. A number of those things have reached a point where we could actually create a startup company and transfer technology into it, so it would attract investment from the kinds of people I was mentioning earlier who don’t like to give money away.

Yuri: So you’ve created several startups, could you elaborate on the ones that have the most potential?

Aubrey de Grey: They’re all doing pretty well. Let me just focus on one as an illustration: Ichor Therapeutics. Ichor is all about macular degeneration, which is, of course, the number one cause of blindness in the elderly. The category in SENS that it comes under is the accumulation of molecular waste products inside cells. They accumulate in different cells in many different ways. It’s a side effect of their normal operation. Different cells accumulate different types of waste products. One of them is a byproduct of vitamin A that is created in the eye as a side effect of the chemistry of vision, and it poisons cells at the back of the eye called retinal pigmented epithelial cells.

What we’ve done is identify enzymes in bacteria that are able to break down this toxic waste product. If they can break it down, the waste product no longer accumulates. We have identified the genes for these enzymes, and we’ve been able to incorporate them into human cells in such a way that they still work. Ichor is pursuing that, and it will probably soon start clinical trials to pursue this as a cure for macular degeneration later this year. This is dry macular degeneration, the major form in the elderly.

Yuri: Could you tell us about some other startups that you’ve spun out from SENS?

Aubrey de Grey: Sure. Ichor was part of LysoSENS. Another one that we’ve spun off is called AmyloSENS. We’ve got a problem of waste products that accumulate not inside the cells but in the spaces between the cells. In theory, those waste products are easier to get rid of, because they’re inherently easier to break down. The way we do it is by actually getting cells to swallow this stuff, internalize it, and then break it down. There are various ways to trick the immune system into doing that. In the case of Alzheimer’s, this was done some years ago, and it’s already working in clinical trials.

Our focus has been on other types of waste products that are similar to the plaques in Alzheimer’s disease, but they consist of different proteins, and they occur in different tissues. We’ve been able to fund a group in Texas that was able to create some antibodies that could break down the extracellular garbage which is actually the number one killer for really old people, people over the age of 110. That’s now been turned into a company.

Another example is a company that’s being run by the person who used to be our Chief Operating Officer. It’s a company focused on organ preservation. It’s well-known that there’s a huge shortage of organs for transplants. Many thousands of people die every year on waiting lists, just waiting for an organ that is sufficiently immunocompatible for them and that happens to be donated by somebody who dies really nearby. That is a requirement for that organ to be given to the recipient fast enough before it breaks down. We want to solve that transport problem and create whole banks of organs with a variety of immunological profiles. In order to do that, we need to be able to freeze them, but in order to freeze them, we need to develop ways that will not cause damage to the organ in the process of freezing. The company we spun out has got a wonderful new technology that is really good at that.

Yuri: Is that Arigos? The company that uses helium persufflation for cryopreservation?

Aubrey de Grey: That’s the one. You are very well-informed!

Yuri: Can you comment on Human Regeneration Biotechnologies?

Aubrey de Grey: That was our first spin-off, actually. It’s now got a shorter name. It’s called Human Bio, and it’s run and funded by a guy named Jason Hope, who was, for some time, one of our most major donors. He’s now focusing his funding on the company. It was initially created to do something very similar to what we’re doing with Ichor in macular degeneration. In that case, it was for atherosclerosis. The target was not this byproduct of vitamin A; instead, it was oxidized cholesterol, and they have kind of run into the sand a little bit on that. We’re trying to reactivate it right now, but they’ve got other interests as well. They’re working on senolytics, drugs that will kill senescent cells. They are potentially going to be quite a big player in a number of different areas at SENS. At the moment, they are a bit stealthy; they don’t need money, because they are funded by this wealthy guy. They are not going around telling everyone all that much about what they are doing, the way that most of these companies are.

Yuri: What about enzymes that are meant to break glucosepane crosslinks? Is there a startup for that?

Aubrey de Grey: We have funded research on glucosepane at Yale University. We’ve funded that for about 4-5 years now. They had a fantastic publication 2 years ago, where they made a huge breakthrough in this area. Essentially, they first had to be able to make glucosepane in large quantities without a high expense. That was published in Science; that’s our highest-profile publication in any area. It was important because it allowed them to proceed with obvious things, such as identifying enzymes that could break it. That was very successful: they have identified half a dozen enzymes that seem to be promising. For a couple of those enzymes, there’s a pretty good understanding of how they work. Now is the right time to create a company out of that, and that’s exactly what’s happening. That company is a month or two from being incorporated, and its funding is established.

Yuri: Great, so we’ll be on the lookout for an announcement for that company to be spun off.

Aubrey de Grey: It’s going to be called Revel.

Yuri: Ah, let’s hope we can one day revel in its accomplishments.

Aubrey de Grey: That’s right!

Yuri: We might have gotten a bit too deep into science for a casual reader. Maybe we can step back and you could elaborate on what you think actually causes aging? I know there are different schools of thought on that in the scientific community so maybe you can share your perspective?

Aubrey de Grey: I get rather sick of this question, actually. You know, there’s nothing that “causes” aging. What causes the aging of a car? You wouldn’t ask that question: you know that that’s a stupid question. All I really want to tell you is that the aging of a living organism is no different fundamentally than the aging of an inanimate machine like a car or an airplane. Therefore, questions like “What causes aging?” are no more sensible for a living organism than they are for a car.

Yuri: If the underlying causes of aging are the same for all organisms, why do you think there’s such a big difference in lifespan between different species: some live for just a few months, while others for centuries?

Aubrey de Grey: The analogy with inanimate machines like cars works perfectly well there too. Some cars are designed to last 50 years, like Land Rovers, for example, but most cars are only designed to last 10 years. It’s just the same for living organisms. Some living organisms have evolved to age more slowly. A perfectly good question is what causes evolution to create this disparity? Some species in a particular ecological niche, say, at the top of the food chain have an evolutionary imperative to age slowly, whereas species that get eaten a lot don’t need to have good anti-aging defenses built into them. That’s really the basis for why there is this variation in the rate of aging across the living world.

Yuri: The more interesting question is when will humanity actually conquer aging?

Aubrey de Grey: It all depends on how rapidly research goes, and that depends on money. Which is why when people ask me, “What can I do today to maximize my chances of living healthy and for a long time?” I tell them to write me a large check. It’s the only thing one can do right now. The situation right now is that everything we have today – no matter how many books are written about this or that diet or whatever – is that basically, we have nothing over and above just doing what your mother told you: in other words, not smoking, not getting seriously overweight, and having a balanced diet. If you adhere to the obvious stuff, you are doing pretty much everything that we can do today. The additional amount that you can get from just any kind of supplement regime, diet, or whatever is tiny. The thing to do is hasten the arrival of therapy for the betterment of what we have today. That’s where the check comes in.

Yuri: Some people probably couldn’t afford to write a sizable check; maybe they can do something else?

Aubrey de Grey: What I always say in relation to that is that the poorer you are, the more people you know who are richer than you. Therefore, the less you can do in terms of writing your own check, the more you can do in terms of persuading other people to write checks.

Yuri: So it’s activism, being vocal about aging research?

Aubrey de Grey: Absolutely. It’s activism and advocacy: it’s all about spreading the word and raising the level of people’s understanding of the fact that aging is the world’s biggest problem.

Yuri: Do you see any increase in funding for longevity research over the past 10 years?

Aubrey de Grey: Things have certainly improved. I mean, there’s more money coming into the foundation, a little bit more money, but there’s a lot more money coming into the private sector, into the companies I mentioned and other companies that have emerged in parallel with us. The overall funding for rejuvenation biotechnology has increased a lot in the past few years, and we need it to increase a lot more. The private sector can’t do everything, not yet, anyway. There will come a time when SENS Research Foundation will be able to declare victory and say, “Listen, everything that needs to be done is being done well enough in the private sector that we no longer need to exist.” For the moment, that’s not true. For the moment, there are still quite a few areas in SENS that are at the pre-investable stage where only philanthropy will allow them to progress to the point where they are investable.

Yuri: It’s great to hear that there is money coming into SENS because from what I understand, there was a time when you had to use your own money to fund the foundation, is that correct?

Aubrey de Grey: That’s right. I inherited 16.5 million dollars of which I donated 13 million. That was back in 2012 before we had any projects that we could spin out into companies. That inheritance was very timely, but the point is that I would still do it even now. If my mother died today, I’d probably do the same thing, because the foundation is still the engine room of the industry. For the foundation, it’s kind of double aid. The more progress we make, the more credible the whole idea becomes, which, of course, improves our ability to bring in money. We are also creating new opportunities where you can invest rather than donate, so it’s kind of a disincentive to donate. There’s a balance there. Of course, every donor is different; some donors are more philanthropically inclined than others.

Yuri: From what I understand, you’ve had some high-profile donors like Peter Thiel who’s been supporting the foundation for a number of years. Is he still a supporter?

Aubrey de Grey: Peter started supporting us in 2006, 12 years ago. He’s actually pretty much phased out now. I understand that. Ultimately, he’s much more comfortable with investing than donating. He wanted to be sure that we’re actually creating something, and sure enough, we are. We speak all the time to his investment advisors, who focus on investment opportunities in the biotech sector, especially in the anti-aging sector. I’m sure that he will continue to contribute financially to this field, though the contributions are quite likely to be focused more on the companies rather than the foundation.

One way in which Peter is donating indirectly right now is that he funded Vitalik Buterin four years ago as a Thiel Fellow under the 20 Under 20 program. That was how and where Vitalik created Ethereum, which of course made Vitalik very wealthy, and Vitalik donated 2.5 million dollars to us a few months ago. He is very much philanthropically inclined. So, Peter is still donating to us by proxy.

Yuri: What about his PayPal co-founder, Elon Musk? Has Peter ever connected you two or maybe you spoke to Elon yourself?

Aubrey de Grey: I have indeed met Elon many years ago, probably 10 years ago. I haven’t met him recently. In general, I think it’s quite unlikely that Elon will get heavily involved in this just because he’s got other things to focus on. It’s a bit like Bill Gates, though in the opposite direction. Bill Gates has pretty much explicitly said that his priority is to help the disadvantaged. He’s much more interested in mosquito nets in sub-Saharan Africa and less interested in people who already have advantages. Elon is kind of at the other end of the spectrum. He is more of a “toys for boys” kind of guy. He’s more interested in space travel and solar energy and so on. The thing is I don’t want to take money away from either one of those two people. I think that both of them are doing fantastic work that really matters for humanity. There are plenty of other people, such as Peter Thiel, who are in the middle, who do understand the enormous value of defeating aging, and who have the vision to understand who is likely to be able to do it, so I don’t want to distract either Elon or Bill from what they’re already doing.

Yuri: Do you think Elon might be moving in a somewhat different direction of mind uploading for circumventing aging?

Aubrey de Grey: Yes and no. I kind of pay attention to what he is doing with Neuralink and what people like Bryan Johnson are doing with Kernel. I am closely connected with those groups. I know a lot of people in that space. At the end of the day, I think they know as well as I do that it’s very, very speculative. Ways in which we might transfer our consciousness, our personality to different hardware, while still satisfying ourselves that we are genuinely the same person after the transfer rather than just creating a new person – those are pretty speculative ideas. There is a long way to go to make them even slightly comparable to something that competes with medical research.

Yuri: So you think that mind uploading, even if theoretically possible, is still far off in the future as something feasible?

Aubrey de Grey: It’s always dangerous these days to say that such and such technology is definitely not going to be developed until some particular number of years in the future. At some point, people said that the game of Go would never fall to a computer, but then AlphaGo came along. However, it is a certainty that the distance that we have to go is much larger in the case of mind uploading than in the case of the boring “wet approach” of medical research.

Yuri: Speaking of AlphaGo and AI, some researchers in the aging space are working AI as a kind of proxy to help us solve biology. What do you think about that approach?

Aubrey de Grey: There is definitely an intersection there. I actually know a lot of people who are at the cutting edge of AI research. I actually know Demis Hassabis, the guy who runs DeepMind, from when he was an undergraduate at Cambridge several years after me. We’ve kept in touch and try to connect every so often. I think it’s reasonable to view these things as very linked. I certainly agree with you that there are some AI researchers who are working on AI precisely because they don’t trust people like me to get the job done by the “wet approach”. That’s fine; they may be right, and if they are right, I’ll be just as happy for them to save my life rather than me saving their lives.

Yuri: Do you think we’re close to having AI help us with biology, or do you think it’s still years away?

Aubrey de Grey: There are some medical AI startups that are looking at ways to use machine learning against aging. One of the most prominent is InSilico Medicine led by Alex Zhavoronkov, which is largely focused on identifying drugs that can work in particular ways. It’s a very important area. I’m sure that we will use AI a lot in medical research in general. Whether we will go as far as supplanting medical research with the mind uploading approach, that’s a different question altogether.

Yuri: One of your most famous quotes is that you think that a person who will live for over 1,000 years has already been born. Do you still think so and what are the chances for, say, a 50-year-old person today to reach what you call Longevity Escape Velocity?

Aubrey de Grey: I certainly think what I used to think, and it is indeed as a result of the concept of the longevity escape velocity. I do not believe that even within the next hundred years, we’re likely to develop therapies that can completely 100% succeed in repairing all the damage that body does to itself in the course of its normal operation. I do believe that we have a very good chance within the next 20-25 years of fixing most of that damage, and most are good enough because it buys time to fix a bit more and then a bit more. The reason it buys time because the body is set up to tolerate having a certain amount of damage without significantly declining function. I think we’ve got a very good chance of getting to that point while we are staying one step ahead of the problem by improving the comprehensiveness of the therapies faster than time is passing.

Yuri: So that is essentially the definition of Longevity Escape Velocity, right?

Aubrey de Grey: Yes, to be precise, Longevity Escape Velocity is the minimum rate at which we will need to improve the comprehensiveness of these therapies subsequent to the point where we get the first ones working so they get us a couple of decades of extra life. The good news is that longevity escape velocity goes down with time, because the more we can repair, the longer it takes for the stuff we can’t repair to become problematic.

Yuri: If you had unlimited funding, how long do you think it would take for us to reach Longevity Escape Velocity or the technology necessary for it?

Aubrey de Grey: It’s actually pretty difficult to answer that question because the amount of funding is kind of self-fulfilling. Every increment of progress that we achieve makes the whole idea more credible, makes more people more interested, and makes it easier to bring in the money to make the next step. I think that, at the moment, unlimited funding could probably let us increase our rate of progress by a factor of three, but that does not mean that we will change the time to get to Longevity Escape Velocity by a factor of three, because when we get even a little bit closer to it, it will be easier to get money, and that factor of three will come down. I think that right now, if we got like a billion dollars in the bank, then, in the next year, we would probably do the same amount of work and make the same amount of progress that we would otherwise make in the next three years. In the year after that, only two years of progress, and in the year after that, only a year and a half, and so on. What that adds up to is that if I got a billion dollars today, we would probably bring forward the defeat of aging by about 10 years. And it’s a lot of lives, maybe 400 million lives.

Yuri: Yes, given that 100,000 people die per day from aging-related causes, it’s a lot of lives.

Aubrey de Grey: Yup.

Yuri: So, you said, “if I had a billion in the bank”. The Chan/Zuckerberg Initiative – they said they are prepared to spend 3 billion dollars to eradicate all diseases by 2099. Maybe they can set aside 1 billion for your work. Did you ever communicate with them?

Aubrey de Grey: All I can say is that my email address is not very difficult to find online. No, we have not been in talks, and they have not made it easy for us to get in touch with them.

Yuri: That’s disappointing, especially given your close geographic proximity and the fact that you probably have an overlapping social and professional network.

Aubrey de Grey: Yes, it is very disappointing. Of course, you can argue that it’s not quite as disappointing as the situation with Calico. Because in the case of Calico we are talking about people with equally deep pockets who have known me for 15 years and who have already decided that aging itself is a thing to target. Zuckerberg, first of all, he never met me, God knows how much he knows about what we even do. Certainly, none of the pronouncements from the Chan/Zuckerberg Initiative indicate that they even understand that aging is a medical problem. They may have a long way to get to the point of even considering this.

Yuri: Yes, they do use some odd phrasing, speaking about “eradicating all diseases”, considering that all age-related diseases have one root cause – the aging process.

Aubrey de Grey: This is part of the problem. People simply should not be using the word “disease” for age-related diseases. The fact is that if a medical condition is age-related, then it’s part of aging, as it mainly affects people who have been born a long time ago. That means that it shouldn’t be described using the terminology that makes people think that it’s a bit like infection. People will often tell each other that I say that aging is a disease or a collection of diseases. But that’s completely wrong: I say the exact opposite. I say that not only should the word “disease” not be broadened to include aging, it should be narrowed to exclude the so-called diseases of old age.

Yuri: So that would be cancer, Alzheimer’s and all kinds of heart conditions…

Aubrey de Grey: Yes, and atherosclerosis, everything that’s bad for people who have been born a long time ago but that very rarely, if ever, affects people in young adulthood.

Yuri: So would you call Alzheimer’s a pathology then? If it’s not a disease?

Aubrey de Grey: I would call it part of aging. The problem is the idea of carving up little bits of aging, pretending that they are separate from each other. They’re not; they’re all parts of – consequences of – a lifelong accumulation of damage.

Yuri: Interesting. There’s been quite a large ongoing effort among the aging research advocacy community to persuade WHO to include aging as a disease in its International Classification of Diseases.

Aubrey de Grey: Yes, it seems to be going quite well, and I am very pleased to see that this effort is being led by some Russians: Daria Khaltourina, who is very much Russian, and by Ilia Stambler, who is from Israel but of Russian extraction. Again, the Russians seem to “get it” much easier than most people and it’s very heartening to me.

Yuri: Do you support this inclusion of aging into ICD as a separate disease?

Aubrey de Grey: The ICD is a little bit different. The “D” in the ICD stands for disease, but the purpose of the ICD is to determine which things medicine should be attacking. It really should be the IC of “medical conditions”. We should be distinguishing medical conditions that are extrinsic, such as infections, from the ones that are intrinsic consequences of being alive, that are age-related. I believe that it would be better if we did that by using different words, but medical conditions of old age are medical conditions, and they ought to be listed in the ICD.

Yuri: I see. Thanks for clarifying! Can I ask you about your new role with Michael West at AgeX and BioTime?

Aubrey de Grey: Michael West and I have been friends for 20 years, and, of course, we have very closely aligned goals in life. We’ve never been able to work together in a formal capacity until now, but we’ve been very much mutual admirers. I’ve always looked up to Mike as someone who, way before anyone else, did something that I thought was impossible with the creation of an actual gerontology research company, as was the case with Geron 20 years ago. He’s done it three times by now: Geron, then Advanced Cell Technology, and now with BioTime.

AgeX is a new subsidiary of BioTime that is about to be floated independently on the stock market. The goal, of course, is very much our goal: damage repair. The area that AgeX is focusing on is stem cells. There are two main themes within AgeX. One of them is stem cell therapy in the normal sense: in other words, injecting stem cells. The particular differentiator that AgeX and BioTime have is the ability to create particularly pure populations of a particular type of stem cells, ones that will only do what you want them to do – they are lineage committed in a particular way. That’s something that other organizations don’t have the ability to do nearly so well, and it’s very important; you want to be able to give the people the type of stem cells they need and not give them the other ones in the wrong place, which might do damage. That’s one side.

The other side of AgeX, which is at a much earlier stage of development, so you shouldn’t be looking out for any products on the basis of this yet, is induced stemness. In other words, it’s giving an organism not stem cells per se but rather reagents that would cause cells already in the body to revert a little bit, become more stem-like and be more able to regenerate the tissues. We already have one compound that has this effect, but we have lots and lots more work to do that will allow this to be done safely and effectively.

Yuri: Is this based on Michael West’s work in planarians, axolotls and other animals that demonstrate the ability to regenerate lost limbs even in adulthood?

Aubrey de Grey: No, not really. Certainly, we pay attention to the regenerative capacity of lower organisms, but the main focus of AgeX’s work is on what happens in early development in mammals, particularly the phase change that happens during early development, which we call the embryonic-fetal transition. It’s a little bit imprecise; we are still characterizing it, and there’s still work to do and stuff to be understood. Basically, what happens is that over a relatively short period of time during development, there is a change in the level of expression in a number of genes; some of them go up, and some go down. The particular change that happens across the entire embryo seems to coincide with – and we think it’s causally related with – the loss of regenerative capacity. In other words, before this transition, a particular type of injury to the embryo is entirely reversed by regeneration, whereas after this transaction, the same type of injury is not reversed, it’s rather patched up with scarring. That’s what happens in the adult as well. We believe that this is very indicative of something that’s going on across the whole body and that has a close relationship with the decline in regenerative capacity and repair capacity against various problems within aging.

Yuri: Is that the COX7A1 gene that was described in a paper in conjunction with Alex Zhavoronkov?

Aubrey de Grey: Yes, COX7A1 is one of the genes that change expression during the embryonic-fetal transition. We do not yet know, or at least we’re not sure, whether it plays a causal role or whether it’s just a marker. We are definitely looking quite a lot at other genes that also change, but COX7A1 is the one we focused on first and most at this point, basically just because it has the sharpest transition in the cell types that we studied so far.

Yuri: Would gene therapy be the vehicle to deliver to the body a way to modulate that gene?

Aubrey de Grey: It might be. Exactly what you do depends on which cell types you decide matter the most in expressing or not expressing a gene and in terms of what gene you want to express. Yes, we might do it with gene therapy. Of course, there are different types of gene therapy. For example, if you want to knock a gene down, you can do RNA interference, which is something that doesn’t involve integrating a new gene into the cell’s DNA. If you want to knock a gene up, you can sometimes also do it by RNA interference, because you can sometimes find the genes that antagonize the gene you want to knock up. If you knock down the gene that antagonizes the gene you want to knock up, then it happens indirectly. There are lots of tricks that are specific to the details of the genetic network, but in general, we would want to manipulate the level of expression and effectiveness of certain genes that change during the embryonic-fetal transition.

Yuri: Can I ask you about a different potential gene therapy, for example, partial reprogramming using Yamanaka factors? Do you think it has any potential as a systemic anti-aging therapy?

Aubrey de Grey: This is the idea that’s actually very similar to what I just described when I talked about the idea of restoration of stemness that we are pursuing at AgeX. Mostly, we don’t know which way is going to work better. We believe that we have a priority in terms of intellectual property, which, of course, is important for investors, but that’s not my problem; I’m focusing on the science.

Obviously, we don’t know which way is going to work best. There are lots of possibilities. The guys who pioneered the idea of partial reprogramming in vivo – there’s a group in Spain led by Manuel Serrano, who is someone I know very well; he’s spoken at one or two of our conferences in Cambridge. He’s a great guy doing a number of other really useful things; he’s got a brilliant new innovation in terms of killing senescent cells as well, which is a completely different area of SENS, of course. More recently, someone in San Diego named Juan Carlos Izpisua Belmonte developed a similar technique that he was able to make work, and his technique involved the intermittent inducible expression of the Yamanaka factors. Essentially, what will determine which of these approaches is the best is not just how well it works but how much harm it does, because there is always a possibility with these things that you will cause cells to become more regenerative that you wished were less regenerative, such as cancer cells, and we need to find a way to control that. It’s possible that AgeX will be able to do this better by using different genes.

Yuri: Okay, great. The reason I knew about Arigos earlier is that I am a big proponent of cryonics. I wanted to ask about your views on cryonics and whether you would personally consider it for yourself?

Aubrey de Grey: Cryonics in general – my position is well known. I’ve been a member of Alcor and a member of its scientific advisory board for 16 years now. I am definitely a very strong supporter. I think that it’s an absolute tragedy that cryonics is still such a backwater publicly and that a large majority of people still believe that it has no chance of ever working. Complete nonsense! If people understood it better, there would be more research done to develop better cryopreservation technologies, and more people would have a chance at life.

The question is what can we do to make cryonics work really well? I certainly don’t have a strong philosophical position with regard to what kinds of revival constitute actual revival and what kinds constitute creating a totally new person from information that you got from the old person. I am not a philosopher, so don’t ask me about that. My personal inclination is that if I have to be cryopreserved at all, and I hope not to be just like any cryonicist, then I prefer to be woken up by being warmed up rather than by being rebuilt from some kind of information restored from slicing and scanning my original brain. Therefore, I am really interested in improving the cryopreservation process: in other words, reducing the amount of damage that is inflicted by the process of cryopreservation and therefore would need to be repaired for successful reanimation; of course, this is along with the damage that the body already had that led to it getting declared legally dead in the first place. Arigos, with its helium persufflation approach, is, in my mind, a massive breakthrough, a breakthrough even bigger than vitrification, which was made 20 or so years ago by Greg Fahy and his peers at 21st Century Medicine when they identified a rather elaborate cocktail of cryoprotectants called M22 that allows biological material of any size to be cryopreserved without any crystallization at all. It eliminated over 90% of the damage that cryopreservation would hitherto have done to biological tissues. After that, it had become the standard of care at Alcor, the Cryonics Institute, KrioRus, and elsewhere.

We need more because the fact is that we still got a lot of cracking that happens – large-scale fracturing – and we’ve also got the toxicity of cryoprotectants, which is mild but non-trivial. Persufflation appears to solve both of these problems pretty much 100% by pumping helium through the vasculature, thereby stopping cracks from propagating, and cooling so much faster that you can vastly lower the concentration of cryoprotectants and still get no crystallization.

Yuri: Did you work with Greg Fahy or Mike Darwin at all on this technology?

Aubrey de Grey: I don’t work with any of these people, but I certainly talk to them. I am not sure what Mike Darwin has done, but Greg, as far as I know, had no work with persufflation itself. Obviously, he pioneered vitrification, but persufflation is something that was first explored in the Soviet Union, I don’t know exactly where, decades ago. Rather like parabiosis, it’s an area that was explored in the Soviet Union and then fell into neglect, and then everyone forgot about it for a long time, and then people in California found out about it and started to do something. The big innovation that Arigos has introduced was using helium, which has a number of advantages for cryonics purposes, but we are definitely building on what was originally done in the Soviet Union.

Certainly, Greg Fahy has been involved in the conversation. He has been advising a lot, and my current understanding is that he is very optimistic about the promise of persufflation, which tells a lot about Greg. The fact is that if persufflation works as well as it’s probably going to work, it’s going to blow Greg’s last 20 years of work out of the water. It takes a lot of honor.

Yuri: Absolutely; Greg is an amazing scientist and human being. I think for him, just as for you, it’s all about defeating aging first, and everything else is secondary. In any case, do you have any other cryonics research planned as part of SENS or Arigos?

Aubrey de Grey: Not as part of SENS, but, of course, I talk to all these people all the time. Something that you might be aware of, which happened very recently, was that Alcor received a very large donation of 5 million dollars specifically for research from Brad Armstrong, one of the people who made plenty of money on cryptocurrencies.

Yuri: It’s great to see crypto millionaires donating money to longevity research.

Aubrey de Grey: Yes, 5 million dollars is a hell of a lot of money for research in cryonics compared to what’s been available up until now. I am actively helping Max More, CEO of Alcor, to decide how to spend it.

Yuri: That’s great to hear. Maybe we’ll get some research done on the restoration of brain activity after cryopreservation. I know that Greg Fahy has done some prior work on assessing LTP preservation, but it’s probably outside of the scope of our interview.

Switching topics, there’s a lot of talk about the biohacking community lately, and a lot of people call themselves biohackers these days. Some claim that taking supplements or working out qualifies as biohacking. Do you consider yourself a biohacker; do you take any supplements or nootropics like Ray Kurzweil or Dave Asprey or do anything else that could be considered as biohacking?

Aubrey de Grey: I don’t take any supplements; I don’t do anything special with my lifestyle. I am not saying that that’s my recommendation for other people. My situation is very strongly that I am prepared to listen to my body. I know that I am just a lucky guy. I am genetically built so that my aging is slow, and I am fortunate enough to have been tested for a total of five times now over the past 15 years; they’ve measured 150 different things in my blood and did all manner of physiological and cognitive tests. I always come out really well, way younger than I actually am, so I should be conservative: if it ain’t broke, don’t fix it.

I eat and drink what I like, and nothing happens. I will pay attention to the situation when it changes, but it’s not changing yet. There’s a couple of things that I do that are bad for my health, especially the fact that I travel so much that I am not getting enough sleep. I think I’ve been coping with that so far as well, and, of course, the reason I do this is to hasten the defeat of aging with all the work that I do. Maybe it’s a net win. The bottom line is that I’m lucky.

I don’t say that Ray Kurzweil is being dumb in doing what he’s doing. On the contrary, Ray is one of the unlucky people; he came down with Type 2 diabetes in his 30s, and his family has had a lot of cardiovascular problems. It probably makes sense for him to be taking all of these supplements in order to largely normalize his rate of aging. For somebody whose rate is normal or better, there’s no evidence that taking supplements could actually have any benefit.

Yuri: What about the cognitive enhancers that Dave Asprey is recommending? Have you ever found anything that works or that you have considered trying?

Aubrey de Grey: No, I let my brain do what it normally does. Even for jet lag or needing to go to sleep, I don’t need these things. I can get to sleep whenever I am tired, whatever time of day it is. I occasionally thought it might be good to have a stash of modafinil just to be able to get through times when I need to stay awake for a long time, but I managed to work my way around those periods, so I haven’t done that either.

Yuri: Maybe your brain is already overactive – I read that you do math problems for fun, and what was this preprint that you published that made a splash in the media?

Aubrey de Grey: I’ve always played with maths for fun. I am reasonably good with certain types of maths, especially those that don’t need too much background knowledge because I don’t even have a degree in maths like graph theory or combinatorics. Yes, earlier this year, I got lucky and made some progress on a very famous long-standing maths problem called the Hadwiger-Nelson problem, and that got a bit of attention. The thing that strikes me the most about all that is that a number of people said, “I always thought Aubrey de Grey was a bit of a lunatic and never paid any attention to what he said about aging, but now that he made progress in this maths problem, he’s obviously smart, so now I will pay attention to what he says about aging.” I think that’s the most fucked-up logic you can possibly imagine, but I’ll take it.

Yuri: From what I understand, despite your background in computer science and no formal training in biology, you actually also have a Ph.D. in biology for your work in mitochondrial respiration back in the 1990s. Is that correct?

Aubrey de Grey: Yes, that’s correct. I benefited from the fact that I’d done my undergraduate degree fifteen years earlier in Cambridge. Of course, that was in computer science, but there’s a system at Cambridge where if you do your undergrad degree there, then you don’t have to be a Ph.D. student to get a Ph.D. from Cambridge. You can just submit published work, it gets evaluated like a dissertation, and you do a thesis defense. Mitochondrial respiration was probably the first area in biology that I got interested in and that I was invited to write a book about, so I did. It included the material for the first six papers of mine, and that’s what I ultimately got my Ph.D. for.

Yuri: It seems that the mitochondrial theory of aging was all the rage back then but has lost a lot of its appeal over the past two decades.

Aubrey de Grey: Yeah, that’s a problem. The reasons why things move in and out of fashion in a biological field are often overly superficial. Nothing’s really changed. Twenty years ago, people were overly breathless about mitochondria and free radicals, and they were neglecting the importance of the shortcomings of those theories, which my first couple of papers helped to repair. I pointed out that you can’t just say “mitochondrial mutations matter because free radicals matter.” You’ve got to flesh it out, and I did flesh it out in a way that nobody else had bothered to do.

Conversely, what happened more recently is that people have swung the other way, saying “there’s various new evidence that free radicals don’t matter, therefore game over.” Again, they are being overly simplistic in the opposite direction. In fact, what this new evidence shows is that certain, particularly simplistic, versions of the free radical theory of aging are not true, but people like me who actually pay attention knew that all along. For me, nothing’s really changed.

Yuri: You make an excellent point that there seems to be some kind of fashion in the field of biology in general or aging research in particular. I wonder why; is it just human nature to jump on the bandwagon and reject all other ideas, or is it groupthink? What is it about science?

Aubrey de Grey: In science, I would say it’s even worse than groupthink. It’s not a question of people just being sheep because they can’t think for themselves. Scientists can think for themselves. The problem in science is that people are forced to follow fashion in order to get money, whether it’s in the form of a grant application, funding, getting promoted, or tenure, which is appalling, because the whole point of science is to go against the grain, to be in the minority of one as often as possible, and to find things out that people didn’t know before. However, the way that the scientific career structure these days actually works opposes that. It’s a tragedy.

Yuri: Indeed, the incentives for going against the grain seem to be misaligned. Is there any way to mitigate this?

Aubrey de Grey: The only solution is to throw a lot more money at science so that people can be career scientists in a way that they used to be 200 years ago when no scientists were without patrons, wealthy noblemen who kept them as pets. They were getting stuff done, and they didn’t have to worry about justifying how they were getting stuff done.

Yuri: Well, let’s hope some philanthropically inclined wealthy noblemen hear you and create more fellowships. Okay, final, semi-serious question: once humanity does reach negligible senescence, what would that do to relationships, family institutions, marriage, and children?

Aubrey de Grey: Nothing at all. The only things that would happen as a result of increased longevity are simply the continuation of societal changes that have already been occurring over the past century. What I see is that as people live longer and stay healthy longer, there’s a rapid increase in the number of divorces, the number of people who have multiple relationships over their lives, and it’s just going to be a continuation of that. It’s not interesting.

Yuri: And overpopulation is never going to be an issue, right?

Aubrey de Grey: This is the one that everybody is worried about, but it’s just so silly that people worry about it. I’ve been saying this since forever – and nobody contradicts my answer, they just ignore it – the answer is that the carrying capacity of the planet, the number of people it can sustain without a problematic amount of environmental impact, is going to go up much faster than the population can possibly go up even if we completely eliminated all death. It’s going to go up as a result of renewable energy, artificial meat, desalination, and all those things. It’s just so painfully obvious, and I’ve been saying this in so many interviews and so many talks, and people just ignore it. I think the only reason people are ignoring my answer is because they need to. They need to carry on believing that aging is a blessing in disguise and thus be able to put it out of their minds, get on with their miserably short lives, and not get emotionally invested in the rate of progress that we will make.

Yuri: Well, let’s hope we can shake them out of their learned helplessness in the face of death and aging.

Aubrey de Grey: Absolutely.

Yuri: Great, thank you so much for this interview! I really look forward to seeing you in Moscow soon and discussing some of these issues in person as well as hearing about your latest achievements in the fight against humanity’s biggest problem!

Aubrey de Grey: Indeed! Thanks so much, Yuri, it’s been great.

Yuri Deigin is a serial entrepreneur and an expert in drug development and venture investments in biotechnology and pharmaceuticals. Yuri brings almost a decade of drug discovery and development experience from his previous role in a biotech startup where he oversaw research and development of original medicines aimed at treating diseases like Alzheimer’s and rheumatoid arthritis. Yuri has a track record of not only raising over $20 million for his previous ventures but also initiating and overseeing 4 clinical trials and several pre-clinical studies, including studies in transgenic mice. He also has experience in pharmaceutical product launch, promotion, manufacturing, and supply-chain management. Since 2013 Yuri also serves as a vice-president of the non-profit Foundation “Science for Life Extension” whose goal is the popularization of the fight against age-related diseases. To further this cause, Yuri frequently blogs, speaks, writes op-ed pieces, and participates in various TV and radio shows. Yuri holds a B.Sc. from the University of Toronto and an M.B.A. from Columbia Business School. Yuri is the CEO of biotech company Youthereum Genetics.

U.S. Transhumanist Party Chairman Gennady Stolyarov II Answers Common Interview Questions

U.S. Transhumanist Party Chairman Gennady Stolyarov II Answers Common Interview Questions

Gennady Stolyarov II


Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party and Chief Executive of the Nevada Transhumanist Party, answers questions posed by Francesco Sacco, which are representative of common points of inquiry regarding transhumanism and the Transhumanist Party:

1. What is Transhumanism and what inspired you to follow it?
2. What are the long-term goals of the Transhumanist party?
3. What are your thoughts on death and eternal life through technological enhancements?
4. Do you feel there are any disadvantages to having access to the cure for death? What advantages are there?

Become a member of the U.S. Transhumanist Party for free, no matter where you reside. Fill out our Membership Application Form here.

See Mr. Stolyarov’s presentation, “The U.S. Transhumanist Party: Pursuing a Peaceful Political Revolution for Longevity“.

Beginners’ Explanation of Transhumanism – Bobby Ridge and Gennady Stolyarov II

Beginners’ Explanation of Transhumanism – Bobby Ridge and Gennady Stolyarov II

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Bobby Ridge
Gennady Stolyarov II


Bobby Ridge, Secretary-Treasurer of the U.S. Transhumanist Party, and Gennady Stolyarov II, Chairman of the U.S. Transhumanist Party, provide a broad “big-picture” overview of transhumanism and major ongoing and future developments in emerging technologies that present the potential to revolutionize the human condition and resolve the age-old perils and limitations that have plagued humankind.

This is a beginners’ overview of transhumanism – which means that it is for everyone, including those who are new to transhumanism and the life-extension movement, as well as those who have been involved in it for many years – since, when it comes to dramatically expanding human longevity and potential, we are all beginners at the beginning of what could be our species’ next great era.

Become a member of the U.S. Transhumanist Party for free, no matter where you reside.

See Mr. Stolyarov’s presentation, “The U.S. Transhumanist Party: Pursuing a Peaceful Political Revolution for Longevity“.

In the background of some of the video segments is a painting now owned by Mr. Stolyarov, from “The Singularity is Here” series by artist Leah Montalto.

Alzheimer’s Drug Turns Back the Clock in Mitochondria – Article by Steve Hill

Alzheimer’s Drug Turns Back the Clock in Mitochondria – Article by Steve Hill

Steve Hill


Editor’s Note: In this article, Mr. Steve Hill discusses an experimental drug, J147, for treating Alzheimer’s disease and also how Alzheimer’s disease is closely linked to aging.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 26, 2018

J147 is an experimental drug that has been shown to treat Alzheimer’s disease, and it also appears to reverse some aspects of aging. It is also poised to enter human clinical trials in the near future, although how it works has been somewhat of a puzzle.

A new study  published in the journal Aging Cell has changed all that, and the results are quite intriguing [1]. Researchers at the Salk Institute have solved the mystery of how J147 works and why it makes old flies, mice, and cells more youthful.

Rejuvenating mitochondria

The drug apparently works because it binds to a protein found in mitochondria, the powerhouses of cells; this, in turn, causes cells to function in a more youthful manner. Mitochondrial dysfunction is one of the hallmarks of aging and is thought to be a key reason why we age and develop age-related diseases [2]. This drug appears, at least partially, to address some of that dysfunction.

Finding the target of J147 was the key to revealing the link between Alzheimer’s disease and the aging process. It was the critical information the researchers needed and was holding the drug back from clinical trials.

Dave Schubert, head of Salk’s Cellular Neurobiology Laboratory, and his team originally developed the J147 drug in 2011. The team screened numerous plant-sourced compounds with the potential to reverse the cellular and molecular signs of aging in the brain. The drug was developed as a modified version of a molecule found in the spice curcumin, a common ingredient in Asian foods such as curry.

Since then, the researchers have shown that J147 can reverse memory deficits, increases the production of brain cells, and slows the progression of Alzheimer’s in mice [3]. However, at that point, they did not understand how J147 worked.

Finding the target

During the new study lead by Dave Schubert and Salk Research Associate Josh Goldberg, the researchers used a number of approaches to find out how J147 worked. They eventually identified that the target of J147 was the mitochondrial protein known as ATP synthase, specifically ATP5A, a subunit of that protein. ATP synthase is involved in the mitochondrial generation of ATP, which cells use for energy.

The researchers demonstrated that by reducing the activity of ATP synthase, they were able to protect neuronal cells from a number of toxicities associated with the aging of the brain. One reason for this neuroprotective effect is thought to be the role of excitotoxicity in neuronal cell damage.

Excitotoxicity is the pathological process by which neurons are damaged and killed by the overactivation of receptors for the excitatory neurotransmitter glutamate. Think of it being a bit like a light switch being turned on and off so rapidly that it ends up causing the light bulb to blow.

Recently, the role of ATP synthase inhibition for neuroprotection against excitotoxic damage was demonstrated in a mouse study [4]. The second study showed that mouse models expressing the human form of mutant ATPase inhibitory factor 1 (hIF1), which causes a sustained inhibition of ATP synthase, were more resilient to neuronal death after excitotoxic damage. This data is consistent with this new J147 study, in which an increase in IF1 in the mice reduced the activity of ATP synthase (specifically ATP5A) and was neuroprotective.

ATP synthase is implicated in aging

ATP synthase has previously been shown to influence aging in C. elegans worms and flies. Given that aging is the greatest risk factor for developing Alzheimer’s disease, it is no surprise that the target of the drug is also involved in the aging process.

The team also revealed that by modulating the activity of ATP synthase, they could influence the levels of ATP and other molecules and were able to encourage healthier, more stable mitochondria during aging. Mice given the compound showed profound changes, appearing to look younger at a cellular and molecular level.

The researchers believe that these results are not only encouraging for the treatment of Alzheimer’s, they suggest that J147 may also be useful in treating other age-related diseases.

“People have always thought that you need separate drugs for Alzheimer’s, Parkinson’s and stroke,” said Dave Schubert. “But it may be that by targeting aging we can treat or slow down many pathological conditions that are old-age-associated.”

With J147 having just completed the FDA required toxicology testing in animals, the next step is phase 1 human clinical trials, and the road to approval begins.

Conclusion

It is very heartening to hear important researchers suggesting that in order to treat age-related diseases, one needs to treat the aging processes themselves. This is the exactly what Dr. Aubrey de Grey and others have been saying for many years. It is good to hear more voices joining the call to tackle age-related diseases at their root: the hallmarks and damages where they all begin.

The process of age-related disease begins long before the familiar signs and diagnoses are made; by targeting the early processes that are not given specific disease names, we might yet defeat horrific diseases, such as Alzheimer’s, which rob us of who we are.

Literature

[1] Joshua Goldberg et al. The mitochondrial ATP synthase is a shared drug target for aging and dementia. Aging Cell, 2018 DOI: 10.1111/acel.12715
[2] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.
[3] Prior, M., Dargusch, R., Ehren, J. L., Chiruta, C., & Schubert, D. (2013). The neurotrophic compound J147 reverses cognitive impairment in aged Alzheimer’s disease mice. Alzheimer’s research & therapy, 5(3), 25.
[4] Formentini, L., Pereira, M. P., Sánchez‐Cenizo, L., Santacatterina, F., Lucas, J. J., Navarro, C., … & Cuezva, J. M. (2014). In vivo inhibition of the mitochondrial H+‐ATP synthase in neurons promotes metabolic preconditioning. The EMBO journal, 33(7), 762-778.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies Steve has provided the community with multiple educational articles, interviews and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Looking Back at 2017: A Year in Rejuvenation Biotechnology – Article by Nicola Bagalà

Looking Back at 2017: A Year in Rejuvenation Biotechnology – Article by Nicola Bagalà

Nicola Bagalà


 

Editor’s Note: In this article, Mr. Nicola Bagalà highlights various events of rejuvenation biotechnology in the year 2017.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 11, 2018

Winter kick-off

This year has been pretty intense, with a lot going on both at LEAF and in the rest of the community. January saw the launch of the LEAF website, shortly followed by both the Lifeboat Foundation and Trust me – I’m a biologist partnering with us. Given that it’s been only a year, we’re amazed at how enthusiastic and supportive the community has been—and how fast it has grown, with nearly 30,000 Facebook followers late in December! We’re also very grateful to our friends at Fight Aging! for their encouragement, support, and appreciation for our work, including honoring us by featuring it on their website!

In February, the CellAge campaign launched in late 2016 concluded successfully, also thanks to the matching fund put together by Longecity. That’s also when LEAF President Keith Comito met Mikhail Batin to discuss the Russian initiative Open Longevity and when Series A funding was announced for LYSOCLEAR, a LysoSENS-based approach to treating macular degeneration.

An eventful spring

The Lifespan Heroes campaign was launched in the spring, and thus far, it has greatly helped us carry out our activities, especially in terms of web development—so thank you to all our generous donors!

In the spring, we also started our advocacy projects with global policymakers. During April 10-15, LEAF Board Director Elena Milova attended a training program conducted by the International Institute on Ageing (INIA) in Saint Petersburg, where she met and interviewed INIA director Dr. Marvin Formosa and former Head of the UN Programs on Ageing Dr. Alexandre Sidorenko.

Later in April, the SENS Research Foundation announced a collaboration on a cellular senescence project with the Buck Institute for Research on Aging.

The month of May was busy with conferences and networking; at the International Longevity and Cryopreservation Summit in Madrid, Elena Milova had the opportunity to interview life extension advocate Didier Coeurnelle, London Futurists Chair David Wood, Dr. Jose Luis Cordeiro, Senior Scientist at CONICET Dr. Rodolfo Goya (we hope to support his studies related to Yamanaka factors in 2018 via crowdfunding at Lifespan.io), and SRF’s Chief Science Officer Dr. Aubrey de Grey. Elena herself gave a talk about effective life extension advocacy methodologies; LEAF board member Paul Spiegel also gave a talk about the need for society to adapt to longer lives. In Paris, the International Cell Senescence Association (ICSA) held a conference discussing senescence triggers, physiological functions of senescence, and pathologies and therapies. We announced the event here.

Our Journal Club series was also launched at the end of May, for a total of eight Journal Club episodes this year, which you can watch here. The Journal Club is a monthly science show on which Dr. Oliver Medvedik hosts guests, and this show is supported by our patrons, the Lifespan Heroes. We broadcast this show live to our Facebook Page every month, where we invite the audience to ask questions and join in with the discussion.

Summer news

In the summer, LEAF and MMTP co-hosted a panel featuring Dr. Alexandra Stolzing, Dr. Aubrey de Grey, and Dr. Oliver Medvedik. This live broadcast included discussions about funding, research progress, and advocacy, providing some interesting insights into the field. They were joined by Alen Akhabaev, one of the project donors who supported the MMTP project on Lifespan.io, as well as Steve Hill and Elena Milova from the MMTP and LEAF.

The AgeMeter campaign was launched on Lifespan.io by Elliott Small in July, and in August, we celebrated the first birthday of our crowdfunding platform—you could say Lifespan.io’s birthday present was the MouseAge campaign launched shortly thereafter. The campaign was successful, and the MouseAge app is now ready and expected to be launched shortly. The use of AI is trending more and more in the field of aging research, so this app is certainly only one of many that will be employed in the future.

A great autumn

The autumn has been, without doubt, the busiest time of the year. The Undoing Aging conference was announced by the Forever Healthy Foundation in September, as was a series of small-scale human senolytic pilot studies by Betterhumans. Almost at the same time as the AgeMeter campaign reached 100% of its goal, Dr. Aubrey de Grey joined our SAB (Scientific Advisory Board), shortly followed by Dr. Robert Shmookler Reis. At this time, SRF and the Spiegel Lab launched a collaboration on developing monoclonal antibodies against glucosepane.

September also saw the Basel Life 2017 conference held in Basel, Switzerland, where Dr. Alex Zhavoronkov chaired the Artificial intelligence and block chain in healthcare and the Aging & drug discovery forums. Insilico Medicine’s Young.AI aging-rate tracking app was officially announced at this conference.

Juvenescence by Jim Mellon and Al Chalabi—a thorough, investor-focused introduction to the science of aging and the world of rejuvenation biotech—was published on September 25. LEAF has published two reviews of the book, which you can read here and here.

Open Longevity ICO, a Russian project focused on conducting clinical trials of geroprotective therapies and introducing diagnoses of aging into clinical practice, was launched in September. It is currently entering the second phase of pre-ICO, and we wish Anastasia Egorova’s team good luck.

In October (which is traditionally considered the Longevity Month) we launched the #IAmTheLifespan campaign, inviting all our supporters to make videos describing what brought them to join our cause, and you can watch some of them here. To help out MouseAge, and for Inktober 2017, our volunteer Laura Weston launched a fundraiser offering her beautiful artwork as a reward for donors.

The Pathways to Healthy Longevity 2017 conference was organized on October 15th by Dr. Ilia Stambler, a famous longevity activist, in Bar Ilan University (Israel), with Prof. Nir Barzilai and Prof. Haim Cohen as key speakers.

In late October and early November, the popular YouTube channel Kurzgesagt published End Aging? and Cure Aging?, which were both created with help from the Lifespan.io team. We saw overwhelming support from old and new members of the community, showing that healthy life extension is much more popular with the public than one might think.

As MouseAge reached and surpassed its goal, news started to spread that WHO was planning to leave healthy aging out of the general programme of work 2019-2023; thanks to the advocacy efforts of the community, though, WHO has received plenty of feedback on the issue and may hopefully reconsider.

During November 8-10th, the TransVision conference was held in Brussels. It was organised by Didier Coeurnelle, the head of HEALES, the Healthy Life Extension Society. Among its other objectives, the Technoprogressive declaration presented at the conference mentions the defeat of aging; it’s good to see that this objective is now considered to be of primary importance by a growing number of organisations.

During December, LEAF took part in Project4Awesome; many amazing videos were made to support us, and we’re really grateful to the community for that. It was a truly beautiful display of generosity, and not the only one; thanks to many fantastic donors, including the mysterious Pineapple Fund creator, the SENS Research Foundation has smashed its funding goals for the year. You can read more about the December highlights here.

Coming up in 2018

In 2018, we will be working towards creating more major media collaborations with awesome content creators to spread further awareness about the problem of aging and the upcoming advent of rejuvenation biotechnologies.

Our web development team will be, and in fact already is, working on improving the overall user experience of our followers and scaling our systems up to meet the needs of a larger user base; we experienced a significant growth in this sense after our collaboration videos with Kurzgesagt were published, and we’re most definitely looking forward to this happening again!

Our Journal Club will, of course, continue discussing and providing commentary on the latest aging research news in the company of special guests from the biogerontology world. More livestream events are in the cards too, so keep an eye on our Facebook page, and subscribe if you haven’t already!

As the community grows larger, so does the need to establish and develop regional presences; our next objective will be starting the Russian chapter of LEAF to engage with a wider audience. Aging is a global problem, so the more communities and audiences we can get involved in the fight against age-related diseases, the better.

LEAF will naturally take part in as many events in the healthy longevity world as possible to keep our readers in the loop. A big must is definitely the March 15-17 Undoing Aging conference in Berlin, Germany, as is the April 22-26 Interventions to Extend Healthspan and Lifespan conference in Kazan, Russia. There will certainly be much exciting news to share, so stay tuned!

The Eurosymposium on Healthy Ageing—a scientific conference organized by the European aging research advocacy group HEALES—will be held in Brussels on November 8-10. It is likely that at least a few of the LEAF team will be at the event, and it is sure to be an interesting one.

Finally, of course, more exciting crowdfunding projects are in the works!

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

For the Last Time: Rejuvenation is Not Immortality – Article by Nicola Bagalà

For the Last Time: Rejuvenation is Not Immortality – Article by Nicola Bagalà

Nicola Bagalà


Editor’s Note: In this article, Mr. Nicola Bagalà explains to us the terms “rejuvenation”  and “immortality” and how they should not be construed to mean one and the same.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, January 10, 2018

When doing science, it is crucially important to have clear, unambiguous definitions. These definitions must be firmly established to avoid confusion and misunderstandings and possibly to prevent people from going around telling everyone that you’re working on something that you’re actually not.

The I-word

It’s not uncommon, especially for outsiders of a given field, to use an inappropriate word to indicate a more complex concept than the word itself conveys—maybe because they think that the two are close enough or possibly because they just don’t see the difference.

For this reason, it’s likely that each field has its own unspeakably profane word; in the field of rejuvenation, that word is the dreaded I-word: immortality.

Before I explain why it is a dreaded word, it’s important to define what the heck it even means. Now, of course definitions are entirely arbitrary, and the same word could mean a different thing to a different person; but if we go with the most intuitive, commonly accepted meaning of “immortality” when nothing else is specified, then we can safely say it describes the quality of someone who cannot die. In other words, it refers to an immortal being could not be killed or die in any way, even if it wanted to. Just like people today who would like to live for an indefinitely long time (like me) are forced to eventually die by aging and are thus stuck without a choice (at least until we figure rejuvenation out), a hypothetical immortal being would be in a similar situation, with no choice to terminate its life because its immortality would force it to live forever. This brief article explains the issue very nicely and concisely.

Now, the way I approach life, immortality wouldn’t be all that bad, because I am skeptical that I’d ever have a reason to want to die. Still, I appreciate that I might be wrong, so if I could choose and wanted to play it really safe, I’d opt for an “immortality switch”; as long as it is on, you’re immortal; if and when you get tired of life, you flip it off and you become mortal again, free to get rid of your own life however you see fit.

Unfortunately, an immortality switch is just as improbable as immortality itself. Think about it: to be immortal, your chance of ever dying of any cause at all should be exactly zero. There’d be no gun, no disease, no poison, no amount of air taken out of your lungs, no stellar explosion capable of terminating your existence. The inner workings—biological or not—keeping you alive should be indestructible, able to withstand forces of any magnitude and keep going under any possible circumstance (including running out of energy). Even without dragging the fabled heat death of the universe into the mix, it’s difficult to imagine how any of this could ever be possible—let alone a switch turning this unlikely ability on and off.

What’s the difference?

I’m not going to go as far as to say that the above is completely impossible; I was trained to make such bold claims only when I can prove them, so I’ll just say that, to the best of my knowledge, this sort of immortality appears to be exceedingly unlikely.

Now, whether immortality is possible or not is an intriguing question, but it is decidedly off-topic in the field of rejuvenation, because rejuvenation is not immortality. If a universal antiviral drug able to wipe the floor with every conceivable virus existed, you wouldn’t call it an immortality drug, because right after leaving the doctor’s office where you got your miracle shot, a grand piano might happen to crush you after a 50-story free fall, and the antiviral drug wouldn’t be especially effective against that particular cause of death. Similarly, rejuvenation would save you from death by age-related diseases, but not by falling grand pianos, sadly.

Yet, both people and the media keep talking about “curing death” and “immortality pills” when the actual topic is rejuvenation biotechnology; this is a cause of particular annoyance to Dr. Aubrey de Grey, whose pioneering work is constantly called an “immortality quest” and similar things. Since immortality reasonably seems a pipe dream and is laden with all sorts of ethical issues and concerns, whether justified or not, this results in a gross misrepresentation of the entire field and a lot of unwarranted bashing of completely legitimate medical research whose only fault is that it aims to prevent the diseases of aging rather than just coping with them.

The same story is true of negligible senescence. If a successful rejuvenation platform were implemented, people would still age biologically, but we would have therapies capable of undoing such aging. Through periodic reapplication of these therapies, the hallmarks of aging would always be kept well below the pathology threshold. In other words, we would still senesce (that is, age), but our level of senescence would stay negligible—that’s where the term comes from. Yet, many people keep calling negligible senescence immortality just like they do rejuvenation biotechnology, whether deliberately or by genuine mistake, thereby providing an excellent strawman for needy critics to beat. This is why the I-word is dreaded in this field, by the way.

Negligible senescence is the expected result of truly comprehensive rejuvenation biotechnologies, and yes, if we got there, our healthspan would be vastly increased, and consequently, so would our lifespan; if you were in perfect health for longer than, say, 100 years, it is a disarmingly trivial consequence that you would live for longer than 100 years. However, whether a negligibly senescent person then lives on forever or not, or ten thousand years from now, someone beats the odds and comes up with a fancy immortality switch, is an entirely different matter that is beyond the scope of the field of rejuvenation biotechnology. Speaking of which, let me reiterate once more what its actual scope is: to eradicate age-related diseases. All the rest, whether consequential effects or downright made-up rubbish, is just unnecessary embroidery.

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

Long Interview with Dr. Aubrey de Grey by Ariel VA Feinerman

Long Interview with Dr. Aubrey de Grey by Ariel VA Feinerman

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Ariel VA Feinerman
Aubrey de Grey


This interview was originally published here

What is ageing? We can define ageing as a process of accumulation of the damage which is just a side-effect of normal metabolism. While researchers still poorly understand how metabolic processes cause damage accumulation, and how accumulated damage causes pathology, the damage itself — the structural difference between old tissue and young tissue — is categorized and understood pretty well. By repairing damage and restoring the previous undamaged — young — state of an organism, we can really rejuvenate it! It sounds very promising, and so it is. And for some types of damage (for example, for senescent cells) it is already proved to work!

Today in our virtual studio, somewhere between cold, rainy Saint-Petersburg and warm, sunny Mountain View, we meet a famous person. I hope everyone knows Aubrey de Grey — the man who fell to Earth in order to change our vision of ageing, to fight with and to finally save us from it! For those of you who are not familiar with him, here is a brief introduction.

Dr. de Grey is the biomedical gerontologist who researched the idea for and founded SENS Research Foundation. He received his BA in Computer Science and Ph.D. in Biology from the University of Cambridge in 1985 and 2000, respectively. Dr. de Grey is Editor-in-Chief of Rejuvenation Research, is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organizations. In 2011, de Grey inherited roughly $16.5 million on the death of his mother. Of this he assigned $13 million to fund SENS research.

I will not ask Dr. Aubrey de Grey any of those stupid questions that journalists usually annoy him with, about his appearance, overpopulation and so on. Instead, we will talk about science and engineering that will rejuvenate our bodies and allow us to be healthy and live longer (I mean really much longer). Because of the recent breakthroughs in many fields, from bionics and applied physics to molecular biology and regenerative medicine, it can (and, I am sure, will) be sooner than you think.

Interview

Feinerman: Hello, Dr. de Grey!

de Grey: Hi — thanks for interviewing me.

Feinerman: In 2012, I read an article by David Sinclair, where he described reversing the loss of mitochondrial function in old mice cells by using NAD+. I felt this was a major change. The past five years have been remarkable! Now every day I read new articles and news about age reversal. In three years, there has been the creation of a few dozen new bioengineering companies whose main goal is to reverse ageing. Billions of dollars are now invested in this area. I believe we will remember 2016–2017 as the most important years. Do you share this feeling?

Note: The first Phase 1 human ageing reversal trials (GDF, Myostatin) will be in a year or two, and George Church discusses how to affordably rejuvenate the whole body! The first version of human CRISPR/Cas9 was created in 2013, and now it is ready for use. In 2015 eGenesis began to work on pigs for xenotransplantation and now they claim they have created retrovirus-free pigs! In 2016 Juan Carlos Izpisua Belmonte has reprogrammed cells by using special factors and reverted back the biological clock in live mice. And this is only a tiny fraction of news!

de Grey: Yes and no. Yes, in the sense that there are indeed more and more exciting breakthroughs being made in the lab — and of course I am very proud that SENS Research Foundation is responsible for some of them. But no, in the sense that there is still a terribly long way to go; we need to fix a lot of different things in order to get rid of ageing, and for some of them we are still at a very early stage in the research.

Feinerman: George Church said that his lab is already reversing ageing in mice and that human applications may only be a few years away. He said: “We have 65 gene therapies that are being tested in mice and larger animals. If they go well, we will go straight into human trials.” Church predicts that age reversal will become a reality within 10 years as a result of the new developments in genetic engineering. However, he warns that age reversal at a molecular level doesn’t necessarily mean that everything else rejuvenates. No one knows what age reversal will mean for humans. Anyway, all that sounds very promising?

de Grey: George is exactly right, both in his urgency and optimism, and also in his caution about how much we don’t yet know.

Feinerman: You have really changed the world’s opinion, but now you are behind the scenes. I regularly read about new breakthroughs in the news while I don’t see much about your work, even though research in SENS is more fundamental in general! When I went to the SENS web page, I was wondered how much you do. This seems like an injustice and can it be fixed?

de Grey: Oh, I’m still quite prominent — I’m still doing just as many talks and interviews as ever. If, to some extent, my contributions are now being overshadowed by other people’s breakthroughs, that’s a good thing! I have always said that my goal is to advance the crusade far enough that I can retreat into glorious obscurity because others are doing my job better than me.

Feinerman: For many people, their appearance is as important as their health. When you say that SENS 1.0 panel of therapies can rejuvenate people from 60 to 30, do they look like 30? Or can they look like 30?

de Grey: Definitely yes. When we thoroughly rejuvenate the inside of the body, the outside is the easy part!

Feinerman: Can we now say that biomedical engineering and biotechnology have entered an exponential phase?

de Grey: I think we can just about say that, yes. It’s very exciting.

Ending Aging Revisited

Feinerman: Your famous book Ending Aging was published 10 years ago. Would you like to make a new version?

de Grey: I probably should, at some point, but it’s not a priority, because the overall approach that we described in that book has stood the test of time: we have made plenty of progress, and we have not come across any unforeseen obstacles that made us change course with regard to any of the types of damage.

Note: If you have not read Ending Aging yet, I suggest you to do it as soon as possible, and to be more comfortable with the ideas we are discussing below, I highly recommend you to read the short introduction to SENS research on the SENS Research Foundation web page. Also, if you are interested in recent news and up-to-date reviews about [anti]ageing and rejuvenation research, the best place to look for is the Fight Aging! blog. Finally, if you are an investor or just curious, I highly encourage you to take a look at Jim Mellon’s book Juvenescence.

Feinerman: You look for bacteria who feed on dead animals to find enzymes capable of breaking glucosepane. Do you consider insects? They can eat nearly everything — and much faster!

de Grey: Nice idea, but we’re looking for a different sort of eating. Insects eat stuff and excrete what they can’t digest, just like us. Bacteria are much more versatile.

Feinerman: Many insects have no special enzymes; instead, they rely on bacteria who do all the work. In any case they are a nice place to look for the enzymes!

de Grey: Yeah, well, not really. Insects have commensal bacteria, yes, but so do we. In general, though, bacteria that are living freely in the environment are more diverse than those in the guts of animals.

Feinerman: How do you find useful bacteria?

de Grey: We are using a “metagenomic” strategy for identifying enzymes that can break glucosepane: we take standard E. coli bacteria, we break one or two of their genes so that they become unable to synthesise one or another chemical (in this case typically arginine or lysine) so that they need to take it up from their surroundings, and then we add random DNA from the environment (which could come from any bacteria, even unculturable ones) and add bits of it to the E. coli. Very occasionally the new DNA may encode an enzyme that breaks glucosepane, and if so, the bacteria will grow even without any arginine or lysine in the environment, if (but only if) we give them glucosepane instead and they break it to create arginine and lysine.

Feinerman: In your book you proposed Whole-body Interdiction of Lengthening of Telomeres (WILT) — the removal of telomerase in all cells in order to prevent cancer and reseed the stem-cell population regularly. Is there any success in that? And wouldn’t it be simpler to use non-integrating telomerase therapy to safely lengthen telomeres, like the approaches developed by Sierra Sciences and BioViva?

de Grey: We are making progress there, yes; in particular we have shown that telomerase-negative stem-cell reseeding works for the blood. However, no, the problem with non-integrating telomerase is that it will extend cancer telomeres just as much as normal cells’ telomeres. I support that research, though, not least because there may be breakthroughs in combating cancer in other ways (especially with the immune system), in which case it would be much safer to stimulate telomerase systemically.

Feinerman: Now we have very precise CRISPR, and removing genes is easier than inserting ones, because you can target the same cell more than once. When we solve the delivery problem, would we be able to apply WILT?

de Grey: Yes, certainly.

Feinerman: Why can’t we remove telomerase locally in compromised tissue?

de Grey: It’s being tried, but it is very difficult to make the removal selective.

Feinerman: There is growing evidence that epigenetic changes are highly organized and may be one of the causes of ageing. This allows some researchers to claim that ageing is a programme. It does not matter, however, how researchers see such changes — as a programme or as damage. By restoring the previous epigenetic profile by means of special reprogramming factors, we can turn an old cell into a young cell, and by resetting the profile, we can turn an adult cell into a pluripotent stem cell. Experiments show that restoring the epigenetic profiles of many cells in vivo rejuvenates an entire organism. What do you think? Maybe should we consider epigenetic changes as another type of damage in the SENS model, calling it EpiSENS?

de Grey: We need to be much more precise with definitions in order to answer your question. Epigenetic changes can be classified into two main classes: shift and noise. Shift means changes that occur in a coordinated manner among all cells of a given type and tissue, whereas noise means changes that occur in some such cells but not others, increasing the variability of that type of cell. Shifts are caused by some sort of program (genetic changes to the cell’s environment), so yes, they can potentially be reversed by restoring the environment and putting the program into reverse. Noise, on the other hand, is not reversible. And we have for several years worked on determining whether it happens enough to matter in a currently normal lifetime. We have not got to a definitive answer, but it’s looking as though no, epigenetic noise accumulates too slowly to matter, other than maybe for cancer (which, of course, we are addressing in other ways).

Feinerman: Should we use reprogramming factors to reverse the epigenetic programme?

de Grey: Probably not. There may be some benefits in doing so, as a way to restore the numbers of certain types of stem cells, but we can always do that by other methods (especially by direct stem cell transplantation), so I don’t think we will ever actually NEED to dedifferentiate cells in vivo.

Feinerman: One thing keeps me out of bed at night: the fear that stochastic nuclear DNA damage and mutations may play a big role in ageing. Ten years ago you proposed that most of the cells which have critical DNA mutations either undergo apoptosis, become senescent, or become cancerous. But if mutations are not critical, cells will live, accumulate them — one broken protein here, another one there — and it will finally lead to malfunction of the organ.

de Grey: Don’t worry. These mutations don’t accumulate nearly fast enough to harm us, because they are prevented by the same machinery that prevents cancer for a currently normal lifetime, and cancer can kill us as a result of only one cell doing the wrong thing, whereas non-critical mutations would need to affect a huge number of cells in order to affect the function of a tissue.

Feinerman: If it is proved that nuclear DNA damage and mutations play a role in ageing, do you have something in your pocket? I believe you already thought on that. How will we fix the problem? Maybe, extensive stem-cell therapy (like the proposed Whole-body Induced Cell Turnover)?

de Grey: Right. But they don’t play a role.

Note: Whole-body Induced Cell Turnover (WICT) consists of the qualitative and quantitative coordination of targeted cell ablation with exogenous cell administration so as to effect the replacement of a patient’s entire set of endogenous cells with exogenous cells (of the same quantity and cell type as the ablated endogenous cells they are replacing) derived from human pluripotent stem cells and directionally differentiated in vitro prior to their administration. The idea of WICT was firstly proposed in 2016 and improved in 2017.

The aim of WICT is the removal from the organismal environment of accumulated cellular and intracellular damage present in the patient’s endogenous cells, including telomere depletion, nuclear DNA damage and mutations, mitochondrial DNA damage and mutations, replicative senescence, functionally deleterious age-related changes in gene expression, and accumulated cellular and intracellular aggregates.

Feinerman: What do you think on the WICT? Combined with WILT, it looks like an all-in-one solution when implemented.

de Grey: The general idea of accelerating cell turnover is definitely a good one. It is a bit like the idea of replacing whole organs: if you replace the entire structure, you don’t need to repair the damage that the structure contains. However, also like replacement of organs, it has potential downsides, because evolution has give us a particular rate of turnover of particular cells, and the function of each of our cell types is optimised for that. So it may end up being complicated, with many pros and cons.

Feinerman: While other rejuvenating therapies (excepting, maybe, OncoSENS) are achievable in the near future and don’t involve special genetic surgery, full allotopic expression has a really long way to go. What do you think of the mimic approaches, for example, NMN, which raises the NAD+ level and restores mitochondrial function in a cell?

de Grey: It may help to preserve health a little, but I think it is very unlikely to extend life by more than a year or two on average (and it could be even less than that). But we are working hard to develop better methods of gene therapy that may make allotopic expression practical sooner than people think.

Feinerman: Oh, can you unveil the mystery?

de Grey: Well, basically we are combining two technologies that are both very very safe (in the sense that they have very low incidence of random DNA damage) but they have complementary limitations. One is CRISPR, which can make small changes very safely to a chosen location in the genome but cannot insert more than very small amounts of new DNA. The other is a very neglected system called BXB1, which can insert large amounts but only into a location that does not exist in the mammalian genome. Our idea is to use CRISPR to insert the BXB1 “landing pad” at a good location and then to use BXB1 to insert our chosen engineered genes at that location. We are developing this at the Buck Institute in Brian Kennedy’s lab.

Feinerman: Thank you for your explanation! However, there is a big problem with all genetic therapies. We need to target every cell in the body, and now it is nearly impossible. Our best delivery systems involving adeno-associated viruses (AAV) available today have only 10–50% efficiency. We should honestly admit that we still have no universal instrument for introducing new genes in an adult human. How will you solve this problem?

de Grey: We believe that the approach I described in my earlier answer will achieve a much higher efficiency, and because its lack of off-target effects, it means it can be used at much higher titer.

Feinerman: The main SENS approach is to rejuvenate our own bodies, but also there is a regenerative medicine which involves tissue and organ engineering. Won’t it be easier to print or grow new organs instead of rejuvenating the old ones? Of course, we cannot replace everything, but we can replace some critical parts: we can grow a new heart, liver, muscles, and, indeed, skin.

Note: Tissue and organ engineering is among the most fast-growing areas of regenerative medicine. Engineers have already bio-printed or grown in bioreactors almost all human organs. Now they are used mostly for testing new therapies or drugs. The main problem why they cannot be used for transplantation now is the vascularisation challenge. While engineers can bio-print or grow arteries and big vessels, they are still unable to create the vasculature — the web of tiny vessels and capillaries within the organ. Companies like Organovo pursue this goal and promise to solve it within next decade.

de Grey: That’s absolutely correct. I expect that in the early days of implementing SENS, some organs will be easier to replace than to repair. However, of course, replacing an organ requires invasive surgery, so we will want to develop repair eventually.

Feinerman: You emphasize that stem-cell research is already a well-advanced field, and SENS has not needed to get involved in this area. As far as I know, many stem-cell therapies are for very specific diseases and not for rejuvenation. Or will we get it as a side-effect?

de Grey: As you know, I don’t think that “diseases of old age” should be called diseases at all — they are parts of ageing, so their treatment is definitely part of rejuvenation. A great example right now is Parkinson’s disease — there are several stem-cell clinical trials in progress or in preparation for it.

Feinerman: Do you mean they are parts of ageing like a runny nose and cough are parts of flu? So treating them separately is as foolish as treating a cough without addressing the flu virus.

de Grey: It’s even worse than that. Treating runny nose and cough makes some sense, because the body will get on with attacking the flu virus anyway, and it makes sense to be less miserable during that time. But with ageing, we’re just talking about different parts of a phenomenon that the body does not know how to attack.

Feinerman: What in your opinion will be the order of arrival of rejuvenating therapies?

de Grey: Well, a lot of the stem-cell side of things is in clinical trials already, and removal of amyloid is there, too, in the case of Alzheimer’s. Next on the list will probably be senescent-cell ablation, which Unity are saying will be in the clinic next year, and removal of intracellular garbage for macular degeneration will also be, courtesy of our spinout Ichor. The other three are harder, but they are all chugging along!

Feinerman: There are about twenty various types of amyloids, we can see some success in removing transthyretin and beta-amyloid. What about others? Can we scale success in removing the above two on the others?

de Grey: I’m very confident that the removal of other amyloids can be achieved using more or less the same methods that have worked against those two. The next one on my list would be islet amyloid, which contributes to diabetes.

Feinerman: As far as I know intracellular junk in the eyes is not lipofuscin per se but A2E, oxidized form of vitamin A. Is there any progress in removing true lipofuscin — the more widespread form of intracellular junk?

de Grey: We have funded some preliminary work on that, but it’s still early. The difficulty is that lipofuscin is very heterogeneous, made up of many different components. Our strategy is to target it more like the way we target the extracellular matrix: rather than breaking it down, we want to identify some key crosslinks that are protecting it from being degraded by our existing lysosomal machinery.

Feinerman: Now everyone is obsessed with “ageing biomarkers” and the “biological clock”. Are they valid conceptions? Is it possible to have a single “clock” for the whole body? Maybe can we just use every type of damage as a biomarker and keep it below certain threshold?

de Grey: I agree with you — ultimately, we still need to fix the damage, so there is not much more that indirect proxy measures can tell us. These indirect measures are useful today, though, when we don’t have those repair therapies, because they help us to see what interventions may (slightly) slow down the accumulation of damage.

WHO, FDA, and New Medicine

Feinerman: FDA has a very long approval for new therapies or drugs. What do you think on medical tourism and biohacking as an alternative way?

de Grey: There have always been places with less restrictive regulatory systems for new drugs — medical tourism is nothing new. I think the key thing we should be doing more of is making better use of those who choose to go abroad to get treated: we should make it as easy as possible for them to report on what treatment they received and how well it worked, any side-effects, etc., for a long time after the treatment, so that such information can be analysed and used to guide future research. The people who provide experimental therapies don’t have any incentive to gather such data themselves, so it usually never gets gathered.

Feinerman: Do the SENS Research Foundation or any associated companies hold regular meetings with the FDA to inform them and clear the way for the new rejuvenation medicine? Some components of the SENS 1.0 panel are already in development or clinical trials, and others will arrive during next 20 years. These new coming medicines use completely different, repair-based rather than compensatory, approaches and need different clinical-trials protocol and a whole new health-care paradigm. The transition period has already begun, and we should use it wisely, otherwise the US may become an outsider in the medical world.

de Grey: I look forward to the day when we have such meetings, but that’s a little way off. That’s OK, though, because companies that are pursuing various components of SENS are indeed having such discussions. The FDA and its counterparts worldwide are being kept up to speed.

Feinerman: We already have many amazing results in the lab which can save human lives just now, but the lack of funding and the heavily regulated medical system don’t give them any chance to be in clinics in the coming years. With the current pace of progress, they will already be outdated before clinical trials. Do you think that translational research becomes the bottleneck?

Note: Even though 90% of US deaths and at least 80% of US medical costs are caused by ageing:

National Institutes of Health budget ($M): ~30,000
National Institute of Aging budget: ~1,000
Division of Aging Biology budget: ~150
Spent on translational research (max): ~10
SENS Research Foundation budget: ~5

These numbers speak for themselves; they are all you need to answer the question of when all of the discussed amazing therapies will be available in the clinics.

de Grey: I think things are improving. The idea of real rejuvenation is becoming more and more accepted. At this point, therefore, I would say that the main bottleneck is still at the earliest stage: the funding for work that is not yet investable.

Feinerman: The current WHO’s agenda is kind of a shame! They know that the fire is coming, but they prepare gasoline to put it out with. Do you agree that the conception of “healthy ageing” is a nonsense? Ageing cannot be healthy because if you are healthy you, well, do not age. The WHO forces people to be more comfortable with ageing instead of fighting with it. They recommend to spend billions to build more nursing houses and buy more wheelchairs instead of investing these money into rejuvenation biotechnology! It’s ridiculous!

de Grey: Well, I think we need to do both things: we need to maintain older people’s quality of life as best we can with the limited tools we have today, and we also need to develop better tools. Terms like “healthy ageing” are indeed double-edged: on the one hand there is, indeed, obviously no such thing, but on the other hand the terminology helps to emphasise that the purpose of all our work is to extend healthspan, with the extension of lifespan being simply a side-effect.

Rejuvenation Research Won’t Fund Itself

Feinerman: When I ask people to donate to SENS Research Foundation, they often say that their a few bucks don’t matter. Of course, they are wrong! Every dollar, even every cent matters! For example, how many people may read this? We assume 10,000. Well, if every of you will donate $50, only $50, per month, it will be over $5,000,000 per year! This sum will double current SENS budget. So, united we can change the world. We cannot and should not wait when governments and big pharma will fund rejuvenation research. (In fact they won’t; they will wait and see the first results.) We can do it ourselves! What can you say to our readers to encourage them?

de Grey: You are saying it really well. One way to say it is to calculate how many dollars it would take to save a life by donating to SENS. I estimate that a budget of $50 millions per year would let us go three times faster than now and would bring forward the defeat of ageing by about a decade. About 400 million people die of ageing in a decade, so that means donating to SENS has a bang-for-the-buck of roughly one life per dollar. No other cause comes anywhere near that.

Feinerman: Another doubt that people usually express is how does SENS Research Foundation do anything meaningful with such a small budget? While NIH and many others have hundreds of millions per year and cannot defeat ageing, SENS has only $5 millions per year. I answer that SENS is a highly efficient organization, goal-directed and result-oriented rather than process-oriented. Everyone can go through the SENS webpage and read last year’s annual report.

de Grey: Thank you! — that is indeed correct. Almost all research that is funded by governments is almost useless, because its effects on health will be tiny. SENS is different because it is a coherent, comprehensive plan for bring ageing under complete medical control.

Note: Unfortunately, I agree with Dr Aubrey de Grey. If you take a close look at NIH or NIA funded work… well… You will find hundreds of publications about obesity, lifestyle, air pollution, and their impact on longevity. Don’t you know that obesity, smoking, and much drinking of alcohol are bad for you? How can this information help us create a new cure against cancer, Alzheimer’s disease, or atherosclerosis? Do we really need another paper on it?

Also you can find many publications about calorie restriction and various genetic manipulations on worms and other model organisms that mimic it. Calorie restriction is everywhere! In the meantime, we have known for twenty years that CR does not work for humans. In 2015, $500,000 was given to projects like “A Large Randomized Trial of Vitamin D, Omega-3 Fatty Acids and Cognitive Decline”. It’s not a joke, it’s a real research work! You can find more here. All that is useless because you cannot use it to produce working rejuvenation therapies. Only a small part of this work is useful in the sense of defeating ageing. Do you know what is the most interesting? It’s all your taxes, all your money! Now you know that.

At the same time really important research projects like work on glucosepane breaker therapy (which will end many ageing pathologies like arterial stiffness, chronic inflammation, hypertension, strokes, and will save many lives) in Spiegel Lab at Yale is permanently underfunded and would be closed last year without financial support from SENS Research Foundation and German entrepreneur Michael Greve. Finally, the cost of implementing the working rejuvenation treatments in old mice would by current estimates be only 1–2% of the Apollo Program. And the same amount of money and time was already spend on Sirtuins which have obviously produced nothing.

Feinerman: Can you say what Project|21 is, why it is so important and how people can help?

de Grey: Project|21 is our name for our appeal to wealthy individuals. We of course welcome donations of any size, but at present it remains the case that most of our income is donated by a small number of wealthy donors, so it stands to reason that we are doing all we can to attract more of those. What other people can do to help is easy — donate what you can, and encourage donations by friends who are wealthier than you!

Note: Project|21 is a new initiative created by SENS Research Foundation to end age-related disease through human clinical trials, starting in 2021, through investment in rejuvenation biotechnology.

Through three new programs, the Bridge fund, The Center of Excellence, and The Alliance Program, Project|21 will deliver the perfect environment for this fusion of opportunity and investment.

$50 million in total funding is required for Project|21, at least half of which will come from the members of SENS Research Foundation’s Group|21. Group|21 will bring together 21 philanthropists, each donating between $500,000 and $5 million. Grants, grassroots efforts, and matching-fund strategies will provide the remaining support. $5 millions was already donated by German Internet entrepreneur Michael Greve. Thank you, Mr. Greve! You are our hero!

Feinerman: Some people prefer to donate not to the whole organisation, but rather to concrete project or lab. Of course, it is not among the most convenient and efficient ways to manage money, but anyway do you consider such an option?

de Grey: Certainly yes. We sometimes have projects that cannot be funded because there is too little “unrestricted” money to go around, but for the most part we are able to make it work, so absolutely, if anyone wants to restrict a donation to a particular project, we are totally happy to work with that.

Feinerman: Now cryptocurrencies and blockchain technologies allow completely new and efficient ways for crowdfunding and investment. We can see as various no-name companies easily raise tens of millions dollars via ICOs for clearly doubtful projects. This occurs while really important areas like generative medicine, rejuvenation biotechnology, or bionics are permanently experiencing an acute thirst of money. Do you consider an ICO for Project|21? I believe it perfectly fits into ICO conditions and requirements!

de Grey: It’s definitely important for us, and we are working closely with various people who are experts in cryptocurrencies. Vitalik Buterin, who created Ethereum, is actually a donor. We very much hope to bring in substantial funding via that route.

Human Psychology, Not the Science, is the Key Issue in Defeating Ageing

Feinerman: When I ask people whether they want to live hundreds of years, many of them say, “No”, but when I ask them, whether they want to look and feel like 30, while being 70, they say, “Yes, of course!” I hope, you got my idea: people are afraid of big numbers. People don’t want to live forever; they just want not to be sick forever, even though big numbers logically emerge from not being sick. Have you ever regretted your claims about big numbers and 1000-year lifespans? People usually understand them in the wrong way. Some your colleagues say that without such claims, your ideas would be much more popular.

de Grey: It has always been a difficult decision. Yes, people are afraid of big numbers, and they are really bad at reasoning about the distant future. But the most important thing, in the long term, is that I am saying what I believe to be true and that I can always give very thorough, logical answers to any challenges. If I had gone out in 2005 saying that we could live to 150 with rejuvenation tech, and people had said why not 250, I would not have had a good answer, and people would not have trusted me. In the end it always works best if you tell the truth.

Feinerman: What do you think of 2013 work “The hallmarks of ageing”, which is obviously inspired by your seven types of damage? They look more sophisticated, and harder to deal with. Anyway, does it mean that researches finally demystified ageing and recognised it as a solvable problem?

de Grey: You’re right, it was definitely a reinvention of SENS. It had quite a few mistakes, but the basic idea of divide-and-conquer damage repair is identical. It is not at all more sophisticated; it’s the same. And yes, it means that mainstream researchers have finally accepted that ageing is now pretty well understood and is solvable.

Feinerman: Although biomedical gerontologists are not afraid to speak about ageing any more, as was the case 10 or even 5 years ago, which itself is a very big step, they are still very skeptical — at least publicly — about our ability to put ageing under medical control in the foreseeable future. You know many of them in person. Is it their real opinion? Maybe, face to face, they are more optimistic?

Note: I think that gerontologists should take a lesson from physicists and engineers. When physicists realised that our Sun uses a nuclear fusion reaction, they were excited by the idea to build a fusion reactor. Being full of courage, they started to work and immediately came across many obstacles. Although the reaction itself is very simple, the processes behind it are complex.

However, engineers haven’t given up or said: “We don’t fully understand these processes, so let’s stop working and study the Sun for 100 years.” They continued to work as hard as they could, built many working prototypes, and now we are much closer to commercial nuclear fusion reactor than ever before. And they are full of optimism! If you ask any physicist, whether it is possible to build such a reactor, the answer would be, “Yes, of course!” And if you ask an engineer, “When can we build it?”, he would probably say: “20–25 years, and it can be much sooner, if we have enough funding.” Sounds similar, doesn’t it?

Ageing is the same. But when you ask a gerontologist whether we can defeat ageing, he would likely call you a crazy. Why? They are both engineering problems!

de Grey: Well, maybe some of them are slightly more optimistic in private than they are in public, but really no — the problem is that they are basic scientists, so they are trained not to believe anything for which they do not have direct evidence. They just don’t like to speculate about time frames, even in private.

Feinerman: Yeah. With the current pace of progress, anything beyond 2030 is an uncertainty. However, what I know exactly is that if we want to have something working in 2030, we should work very hard in the right direction right now. So why do many [anti]ageing researchers consciously or unconsciously choose the most inefficient and ineffective way — altering metabolism via genetic manipulations or medications to only slightly possibly modestly slow down ageing — and use that as a proof (!) that we cannot radically extend human health and lifespan? Such an example is ridiculous by itself and nearly impossible in any research or engineering area, except biomedical gerontology!

de Grey: That is not something specific to anti-ageing research. In all research areas, the leaders always think they are right and take a long time to understand radically new ideas.

Feinerman: Maybe that is the reason? Maybe we need to have fewer gerontologists who merely study ageing and more biomedical engineers who repair damage? In other words we should switch our focus from ageing research to rejuvenation engineering. Since ageing is an engineering problem, then from the gerontologists’ point of view it looks like “not my job” to reverse it.

de Grey: Exactly. The main problem is that until “only” 17 years ago, no one had any coherent plan for fixing ageing, so it made sense to carry on treating gerontology as a basic science in which the priority was to discover more about it rather than to manipulate it. And 17 years is not very long in science, so the people who are most senior and influential are still the people who formed their mindset in the pre-rejuvenation era.

Feinerman: Unfortunately, the vast majority of biomedical engineers, those who do actual rejuvenation research, do not want to be associated with any [anti]ageing business and life extension, are not involved in longevity discussions, and usually keep silence. When pressed, they, however, are not very optimistic about life extension. It’s quite surprisingly to hear such claims from cutting-edge researchers, especially from those who recently promised to print or grow all vascularised human organs by 2035 and grow new limbs by 2030. If it is not about life extension, then what is it all about? Why do they behave in such a manner? Because of the pro-ageing trance? Or because they are too specialised and cannot see the whole picture?

For example, cell engineers make predictions as though there will be no progress in bionics, and bionics engineers make predictions as though there will be no progress in cell engineering. Each technology alone will not likely be te game changer, but when combined their impact will be enormous!

de Grey: You’ve got it. These technologies are developed largely independently of each other, so their leaders are largely unaware of how much progress is being made in the other areas. Since SENS is a divide-and-conquer approach, one cannot be optimistic about the overall outcome unless one is informed about all the components. That’s the main reason why I ran the Cambridge conference series starting in 2003, which is being revived in Berlin in March 2018 — to bring the leaders of these fields together.

Feinerman: Thank you very much for your amazing interview! Our conversation was wonderful! I wish you all your wishes come true as soon as possible. When we succeed, I hope we will shake our hands one hundreds years from now, walking along the waterfront of Mars City, which Elon Musk has promised to start to building in 2020s. Ah, and when you meet with him, remind him, please, that we will not be able to colonise Mars until we defeat ageing — because microgravity and cosmic radiation have the same implications on the human organism as premature ageing!

de Grey: Thank you for your support!

Afterwords

We live in the exciting era, The Era of Very Rapid Progress in science and technology — an era when many things which were merely science fiction only five years ago are common now, and things that are no more than science fiction now will be common in next five years. At the same time we live in The Era of Great Uncertainty — an era when our small everyday life decisions may have a huge impact on next several decades. One step to the right — and we may defeat ageing in twenty years. One step to the left — and the whole research areas will stagnate for another twenty years (as occurred in the case of glucosepane research).

New rejuvenation medicine is still very young and fragile, like the first spring flower after a dry and cold winter. In these days it especially needs our support! Even in such relatively advanced fields like stem cell or cancer research, there are gray, underfunded, and under-researched areas we need to care of.

Of course, you wish to know the time frames — when will we defeat ageing? You wish to know, will you personally benefit? Nobody knows. I intentionally did not ask Dr. Aubrey de Grey about the time frames and predictions. There will be no more time frames. Enough. Because they give you an illusion that some good clever guy will do all the work needed, while you may just relax, wait when he finishes, and “live long enough to live forever”. But he won’t! It is too big, too ambitious a project for one person. Now you know — your future is only in your hands. Not “live long enough…” but “work long enough…”! I always say that scientific and technological progress is a function of efforts — not of the time. The only way to get rid of a painful uncertainty and get to the definitive answer is to support meaningful rejuvenation research right now!

How can you help? Well, if you are a researcher yourself, then spend your time and money on the meaningful repair-based approach, which will produce working rejuvenation therapies in the foreseeable future. If you are a businessman — donate money to the SENS Research Foundation and its allies — Project|21, Methuselah Foundation, Forever Healthy Foundation, Life Extension Advocacy Foundation, or directly support research groups. Invest in the associated rejuvenation companies or found your own. If you are a celebrity, then use your fame to give attention to the problem and such research. If you are an ordinary person, well, you can encourage your more influential friends and do almost the same — just scale your abilities!

Some of you may ask: is it real? I hope we gave you enough evidence. Yes, of course, it’s real. Mover, it’s already happening! The right question, however, is whether it is happening fast enough to help us — currently living adult persons. And the answer is, probably, no. Of course, there may (and likely will) be many unexpected breakthroughs, but we should not rely on probability and scientific serendipity when we talk about human lives (especially our own). We should rely on a well-written plan, a reasonable budget and our efforts.

So the next question is, “Can we speed up the progress?” Yes, we can! All we need to do is what Dr. Aubrey de Grey said many times before and what I have just said above — unite against our main enemy and help researchers. But will we? Although people rarely think and behave rationally, I prefer to be cautiously optimistic! See you on Mars!

https://www.nextbigfuture.com/2017/12/wake-up-people-its-time-to-aim-high.html

Ariel VA Feinerman is a researcher, author, and photographer, who believes that people should not die from diseases and ageing, and whose main goal is to improve human health and achieve immortality.

The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

The Best of the SENS AMA – Article by Steve Hill and Aubrey de Grey

Steve Hill

Dr. Aubrey de Grey


Editor’s Note: In this article, Steve Hill highlights the Ask Me Anything on Reddit held on December 7th by Dr. Aubrey de Grey.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 13, 2017

 

Dr. Aubrey de Grey from the SENS Research Foundation (SRF) did an Ask Me Anything on Reddit on December 7th, and there were many great questions and answers; we thought it would be a great time to summarize some of the best ones and offer a little commentary.

What do you think were the biggest wins of the last couple of years in SENS-relevant advocacy, research, and development? What has moved the needle?

There have been lots. On the research, I would highlight our paper in Science two years ago, which shows how to synthesize glucosepane, and our paper in Nucleic Acids Research one year ago, which shows simultaneous allotopic expression of two of the 13 mitochondrial genes. Both of those projects have been greatly accelerated in the meantime as a result of those key enabling breakthroughs; watch this space.

On advocacy, I think the main win has been the arrival of private capital; I would especially highlight Jim Mellon and his Juvenescence initiative because he is not only a successful, energetic and visionary investor, he is also a highly vocal giver of investment advice.

We are pleased to have been involved with the second project mentioned here, as we hosted the MitoSENS project at Lifespan.io, where it raised 153% of its initial fundraising goal. Less than a year later, after raising this money, it went on to publish the groundbreaking study showing that backup copies of mitochondrial genes could indeed be created in the nucleus. Dr. de Grey originally proposed the idea over a decade ago amid much scepticism; it is really good to see that years later he has been vindicated. This is the power of crowdfunding and how we as a community can make big changes in science by working together.

How do you feel about the impact of groups like LEAF advocating and reporting on rejuvenation biotech? Has the advocacy and reporting of these groups made your life any easier?

Massively! A huge thing that I say all the time is that advocacy absolutely relies upon the diversity of its messengers. Different people listen to different forms of words, different styles of messaging, etc. The more, the better.

It’s good to know that our work is appreciated and helping. Working together as a community is essential for progress, so it was nice to see this question and response from someone we respect a great deal.

We have said many times before effective advocacy efforts are just as important as the research itself. Professional advocacy has the potential to increase public support and funding, paving the way for the arrival of rejuvenation biotechnology. In the past decade or so, advocacy has mostly been left to volunteers and people such as Dr. de Grey.

Popular causes attract celebrities, public support, funding and investment; if we want a revolution in medicine and how we treat aging, then we must popularize the movement. There has been a serious shortage of full-time and organized advocacy; therefore, we decided to create LEAF to support groups like the SRF, advocate to popularize the cause, and help to raise much-needed funds for research efforts. We are only able to do this thanks to the support of the community, and we are extremely grateful to our Lifespan Heroes for helping us to do the work we do.

Aside from funding, what do you consider to be a burden or delay for your type of research?

Nothing. Seriously, nothing at all. We have the plan, and we have the people. It’s all about enabling those people by giving them the resources to get on with the job.

Indeed, funding for research is one of the four major bottlenecks slowing down the development of therapies that address the aging processes. The more funding the field gets, the more projects can be launched, the sooner breakthroughs can potentially happen, and the greater the benefits will likely be for all of us.

Is there anything new you are able to say about the breaking of cross-links in the extracellular matrix?

Absolutely. Short story, we now have a bunch of glucosepane-breaking enzymes, and we are within a few months of spinning the work out into a startup.

A suspected cause of degenerative aging is the accumulation of sugary metabolic wastes known as advanced glycation end-products (AGEs). These are wastes that are, in some cases, hard for our metabolism to break down fast enough or even at all. Some types, such as glucosepane, can form cross-links, gumming together important proteins such as those making up the supporting extracellular matrix scaffold.

The properties of elastic tissues (skin and the blood vessel walls) derive from the particular structure of the extracellular matrix, and cross-links degrade that structure, preventing it from functioning correctly. AGEs’ presence contributes to blood vessel stiffening with age, and it is implicated in hypertension and diabetes.

That SRF now has candidate enzymes is very significant because it means that there are now potential ways to remove these crosslinks from our tissues. There are many types of crosslinks, and we already know of compounds and drugs that can break other kind of crosslinks; the major problem is glucosepane, as it lasts a very long time, and, so far, nothing is known to remove it. Given that other types of crosslinks can be removed, Dr. de Grey rightly thought that there must be ways to remove (cleave) glucosepane from tissues; now, it seems that we are a step closer to that potentially becoming a reality.

If the SRF is successful in finding ways to break glucosepane crosslinks, this has huge implications for diabetes, hypertension and aging. It is great to hear that the organization is now reaching the point at which it is almost time to develop this as a therapy by creating a startup company.

It seems likely that artificial intelligence will be a necessary tool in order to reach longevity escape velocity. I was wondering how much of a role does artificial intelligence play in your research? Is this something you devote many resources to?

We don’t, but that is because other major players in this field (and good friends of mine), such as Alex Zhavoronkov and Kristen Fortney, are doing it so well already (with Insilico Med and BioAge, respectively). Check out the BioData West conference that will occur in SF a couple of days before our Undoing Aging conference in Berlin; I will be chairing a session on this.

We believe that the application of AI and, in particular, machine learning will prove to be a very valuable tool for research in the coming years. Such systems are ideally suited for high-throughput, laborious tasks that also require high attention to detail and would take humans a long time to do. Drug discovery, image analysis and many more tasks in the lab could potentially be automated, saving time and freeing up researchers to work on other critical tasks.

We are proud to have hosted the MouseAge project this year, which is an AI-based visual aging biomarker application that helps researchers determine the age of mice without the use of harmful tests. In a few months, researchers will be able to use the MouseAge application in the lab to help speed research progress up. This is just one example of how AI can be used in aging research and how the community helped to make it happen.

Given current funding, how far away from robust mouse rejuvenation do you think you are?

My estimate is 5-7 years, but that’s not quite “given current funding”. My overoptimism in saying “10 years” 13 years ago consisted entirely of overoptimism about funding – the science itself has not thrown up any nasty surprises whatsoever – but, nonetheless, I am quite optimistic as of now about funding, simply because the progress we have made has led to a whole new world of startups (including spinoffs from the SENS Research Foundation) and investors, so it’s not only philanthropy anymore. Plus, the increase in overall credibility of the approach is also helping to nurture the philanthropic side. We are still struggling, that’s for sure, but I’m feeling a lot surer that the funding drought’s days are numbered than I felt even two or three years ago.

Robust mouse rejuvenation (RMR) has long been a goal for the SENS Research Foundation, going back to when the SENS approach was initially proposed. RMR was originally outlined as being able to demonstrate and replicate SENS to double the remaining life expectancy of an already aged mouse. This would not mean the first RMR would be a total implementation of all the SENS approaches or that rejuvenation would need to be absolute; it would be a first pass to demonstrate the viability of multiple SENS approaches combined to produce robust results.

Being able to achieve a first-pass RMR could do much to convince academia that the repair approach to aging is plausible and attract more funding and interest in the approach. While RMR working in mice may not sound that exciting, it has huge implications for the field and potentially the rate of funding and progress.

How confident are you still in your previous prediction that humans will be able to control aging by 2029?

I think we’ve slipped a few years, entirely because of lack of funding. The tipping point will be when results in mice convince a critical mass of my curmudgeonly, reputation-protecting expert colleagues that rejuvenation will eventually work, such that they start to feel able to say so publicly. I think that’s on the order of five years away.

We think that the tipping point could well be if senolytics have the same result in humans as they have in mice. Enhanced tissue repair and regeneration in older people would be a very strong case for the repair approach to aging and almost certain to convince the academics sitting on the fence.

Certainly, if AGE breakers could be demonstrated to work in humans, this would also go a long way towards not only convincing academia but also grabbing public interest. Removing AGEs from the skin may potentially reverse wrinkles, for example, and restore skin elasticity, offering a very visual demonstration of repair being plausible.

There is almost certainly going to be a tipping point at which the bulk of academic and public support swings in favour of a repair approach to aging; the only question is when? Well, the sooner the basic science can be done and moved to translational research, the sooner we can all potentially benefit from these technologies. This makes supporting both the research and advocacy of rejuvenation biotechnology very important for progress.

 

About Dr. Aubrey de Grey

Dr. Aubrey de Grey is a biomedical gerontologist based in Cambridge, UK and Mountain View, California, USA, and is the Chief Science Officer of SENS Research Foundation, a California-based 501(c)(3) charity dedicated to combating the aging process. He is also Editor-in-Chief of Rejuvenation Research, the world’s highest-impact peer-reviewed journal focused on intervention in aging. He received his BA and Ph.D. from the University of Cambridge in 1985 and 2000 respectively. His original field was computer science, and he did research in the private sector for six years in the area of software verification before switching to biogerontology in the mid-1990s. His research interests encompass the characterisation of all the accumulating and eventually pathogenic molecular and cellular side-effects of metabolism (“damage”) that constitute mammalian aging and the design of interventions to repair and/or obviate that damage. He has developed a possibly comprehensive plan for such repair, termed Strategies for Engineered Negligible Senescence (SENS), which breaks aging down into seven major classes of damage and identifies detailed approaches to addressing each one. A key aspect of SENS is that it can potentially extend healthy lifespan without limit, even though these repair processes will probably never be perfect, as the repair only needs to approach perfection rapidly enough to keep the overall level of damage below pathogenic levels. Dr. de Grey has termed this required rate of improvement of repair therapies “longevity escape velocity”. Dr. de Grey is a Fellow of both the Gerontological Society of America and the American Aging Association, and sits on the editorial and scientific advisory boards of numerous journals and organisations.

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

SENS: Progress in the Fight Against Age-Related Diseases – Article by Nicola Bagalà and Steve Hill

Nicola Bagalà

Steve Hill


Editor’s Note: In this article, Mr. Nicola Bagalà and Steve Hill discuss the progress that the SENS Research Foundation has made in tackling the aging processes. Below is a brief summary of some of the highlights of their research efforts.  This article was originally published by the Life Extension Advocacy Foundation (LEAF).

                   ~ Kenneth Alum, Director of  Publication, U.S. Transhumanist Party, December 8, 2017

 

 

Today, there are many drugs and therapies that we take for granted. However, we should not forget that what is common and easily accessible today didn’t just magically appear out of thin air; rather, at some point, it used to be an unclear subject of study on which “more research was needed”, and even earlier, it was just a conjecture in some researcher’s head.

Hopefully, one day not too far into the future, rejuvenation biotechnologies will be as normal and widespread as aspirin is today, but right now, we’re in the R&D phase, so we should be patient and remind ourselves that the fact that we can’t rejuvenate people today doesn’t mean that nothing is being done or has been achieved to that end. On the contrary, we are witnessing exciting progress in basic research—the fundamental building blocks without which rejuvenation, or any new technology at all, would stay a conjecture.

In particular, SENS Research Foundation (SRF), a pioneering organization of the field, is sometimes unjustly accused by skeptics for failing to produce results. But produce results it has, and many at that. Skeptics either decide to ignore them or do not have access to reliable sources. For the benefit of the latter, we’ll discuss below what has been achieved by SRF over the past few years, in relation to the infamous “seven deadly things”, the seven categories of damage that aging causes as described in the SENS repair approach.

Mitochondrial mutations

In a nutshell, a mitochondrion is a cell component that is in charge of converting food nutrients into ATP (adenosine triphosphate), a chemical that powers cellular function. Your DNA is contained within the nucleus of each of your cells, but this isn’t the only DNA in your body; mitochondria have their own DNA (known as mtDNA), likely because, at the dawn of life, they were independent organisms that eventually entered a symbiotic relationship with eukaryotic cells, such as those found in our bodies.

Unfortunately, as mitochondria produce ATP, they also produce so-called free radicals as a byproduct—atoms with unpaired electrons that seek to “pair up” with other electrons, and to do so, they’ll gladly snatch them from other molecules nearby, damaging them. As free radicals are created by mitochondria, they’re very close to mtDNA, which is thus very susceptible to being damaged and undergoing mutations.

Mitochondria with damaged DNA may become unable to produce ATP or even produce large amounts of waste that cells cannot get rid of. To add insult to injury, mutant mitochondria have a tendency to outlive normal ones and take over the cells in which they reside, turning them into waste production facilities that increase oxidative stress—one of the driving factors of aging.

MitoSENS: How to solve this problem, and how far we’ve got

Cell nuclei are far less exposed to free-radical bombardment than mitochondria, which makes nuclear DNA less susceptible to mutations. For this reason, the cell nucleus would be a much better place for mitochondrial genes, and in fact, evolution has driven around 1000 of them there. Through a technique called allotopic expression, we could migrate the remaining genes to the nucleus and solve the problem of mitochondrial mutations.

Human-made allotopic expression was a mere theory until late 2016, when, thanks to the successful MitoSENS crowdfunding campaign on Lifespan.io, a proof of concept was finally completed. Dr. Matthew O’Connor and his team managed to achieve stable allotopic expression of two mitochondrial genes in cell culture, as reported in the open-access paper[1] they published in the journal Nucleic Acids Research. As Aubrey de Grey himself explains in this video, of the 13 genes SRF is focusing on, it’s now managed to migrate almost four. This had never been done before and is a huge step towards addressing this aspect of aging in humans. In the past few months, the MitoSENS team has presented its results around the world and worked on some problems encountered in the project.

A list of SRF-funded papers on the topic of mitochondrial mutations can be found here. A more detailed description of its intramural MitoSENS research can be found here.

Lysosomal dysfunction

Lysosomes are digestive organelles within cells that dispose of intracellular garbage—harmful byproducts that would otherwise harm cells. Enzymes within lysosomes can dispose of most of the waste that normally accumulates within cells, but some types of waste, collectively known as lipofuscin, turn out to be impossible to break down. As a result, this waste accumulates within the lysosomes, eventually making it harder for them to degrade even other types of waste; in a worst-case scenario, overloaded lysosomes can burst open and spread their toxic contents around.

This eventuality is especially problematic for cells that replicate little or not at all, such as heart and nerve cells—they’ve got all the time in the world to become swamped in waste, which eventually leads to age-related pathologies, such as heart disease and age-related macular degeneration.

LysoSENS: How to solve this problem, and how far we’ve got

As normal lysosomal enzymes cannot break down lipofuscin, a possible therapy could equip lysosomes with better enzymes that can do the job. The approach suggested by SRF originates with ERT—enzyme replacement therapy—for lysosomal storage diseases. This involves identifying enzymes capable of breaking down different types of intracellular junk, identifying genes that encode for these enzymes, and finally delivering the enzymes in different ways, depending on the tissues and cell types involved.

SRF funded a preliminary research project on lipofuscin clearance therapeutics at Rice University[2] and another project relating to atherosclerosis and the clearance of 7-ketocholesterol[3] (a lipofuscin subtype), which eventually spun into Human Rejuvenation Biotechnologies, an early-stage private startup funded by Jason Hope.

A LysoSENS-based approach is currently being pursued by Dr. Kelsey Moody, who used to work at SRF. Dr. Moody has been working on an ERT treatment for age-related macular degeneration. The treatment consists in providing cells of the macula (a region of the eye’s retina) with an enzyme capable of breaking down a type of intracellular waste known as A2E. The treatment, called LYSOCLEAR, is being worked on by Moody’s company Ichor Therapeutics, which earlier this year has announced a series A offering to start Phase I clinical trials of its product.

If LYSOCLEAR proves successful, it could pave the way for future LysoSENS-based therapies to treat lysosomal dysfunction in different tissues.

A list of SRF-funded papers on the topic can be found here.

Cellular senescence

As cells divide, their telomeres—the end-parts of chromosomes protecting them from damage—shorten. Once a critical length has been reached, cells stop dividing altogether and enter a state known as senescence. Senescent cells are known to secrete a cocktail of chemicals called SASP (Senescence Associated Secretory Phenotype), which promotes inflammation and is associated with several age-related conditions.

However, senescent cells are a bit of a double-edged sword; as explained by Professor Judy Campisi during RB2016, as long as they’re not too numerous, senescent cells carry out an anti-cancer function and may promote wound healing; however, too many of them have the opposite effect, and on top of that, they induce neighboring cells to undergo senescence themselves, starting a dangerous spiral.

Normally, senescent cells destroy themselves via programmed cell death, known as apoptosis, and are then disposed of by the immune system, but some of them manage to escape destruction, and as the immune system declines with age, this gets worse.

The result is that late in life, senescent cells have accumulated to unhealthy amounts and significantly contribute to the development of age-related diseases. Osteoarthritis, cardiovascular diseases, cancer, metabolic disorders such as diabetes, and obesity are all linked to the chronic age-related inflammation to which senescent cells contribute.

ApoptoSENS: How to solve this problem, and how far we’ve got

The proposed SENS solution is straightforward: if senescent cells become too numerous, then they need to be purged. Since they are useful in small amounts, the optimal solution would be periodically removing excess senescent cells without eradicating them entirely—and more importantly, leaving other cells unharmed.

This could potentially be achieved by either senolytic drugs or gene therapies that selectively target senescent cells and trigger programmed cell death. Indeed, a great deal of recent focus by researchers have been on finding ways to remove senescent cells using senolytic therapies.

Another approach that could complement senolytics is to address why the immune system stops clearing senescent cells effectively in the first place. This approach focuses on macrophages and other immune cells involved in clearing senescent cells, aiming to reduce inflammation so that these cells begin to function properly again. The irony is that as inflammation rises with age, the immune system that is supposed to clear senescent cells and keep inflammation levels down actually starts to create more inflammation and becomes part of the problem by not doing its job properly.

SRF has funded a number of studies on the subject of cellular senescence, and it’s recently begun working on a project in collaboration with the Buck Institute for Research on Aging, which is focusing on the immune system and its role in clearing senescent cells. Another extramural project, again with the Buck Institute, is focussed on SASP inhibition.

Senescent cell clearance has been all the rage for the past two years or so; Lifespan.io has hosted the MMTP project, which focused on testing senolytics in mice, and this was later followed by CellAge’s project to design synthetic biology-based senolytics.

There are other companies that have joined the race to add senescent cell clearance to the standard toolkit of doctors, such as Unity Biotechnology and Oisin Biotechnologies.

Unity’s approach uses a drug-based approach to senolytics and is scheduled to enter human clinical trials in 2018. A number of other research teams are also developing drug-based approaches to removing senescent cells, and the competition looks set to be fierce in this area in the coming years.

Oisin’s approach, which we discussed here, makes use of suicide genes and hopefully will be tested in clinical trials not too far into the future, thanks to venture funding presently being collected. If this system can be made to work, it will allow very selective targeting of senescent cells by destroying only those giving off a target gene or genes. Thus, if a unique gene expression profile for senescent cells is determined, it would mean only those cells were destroyed, with less risk of off-target effects.

Oisin owes its existence to the SENS Research Foundation and the Methuselah Foundation, which provided the necessary seed funding. Kizoo Technology Ventures has also invested in Oisin.

Extracellular crosslinks

The so-called extracellular matrix is a collection of proteins that act as scaffolding for the cells in our body. This scaffolding is rarely if ever replaced, and a really bad consequence of this is that its parts eventually end up being improperly linked to each other through a process called glycation—the reaction of (mainly) blood sugar with the proteins that make up the extracellular matrix itself.

The resulting cross-links impair the function and movement of the linked proteins, ultimately stiffening the extracellular matrix, which makes organs and blood vessels more rigid. Eventually, this leads to hypertension, high blood pressure, loss of skin elasticity, and organ damage, among other problems.

While there are different types of cross-links—known as AGEs, short for advanced glycation end-products—glucosepane is arguably the worst, being the most common and long-lasting of all, and the body is very ill-equipped to break it down.

GlycoSENS: How to solve this problem, and how far we’ve got

In order to eliminate unwanted cross-links, the SENS approach proposes to develop AGE-breaking molecules that may indeed sever the linkages and return tissues to their original flexibility. Of course, in order to do so, crosslink molecules need to be available for research to attempt to combat them with drugs, and especially in the case of glucosepane, this has been a problem for years.

Glucosepane is a very complex molecule, and very little of it can be extracted from human bodies, and not even in its pure form. This has been greatly hampering the progress of research against glucosepane, but thankfully, this problem is now solved thanks to a collaboration between the Spiegel Lab at Yale University and the SENS Research Foundation, which financially supported the study. It is now possible to fully synthesize glucosepane, allowing for researchers to create it on demand and at a cost-effective price.

The Spiegel Lab’s scientists are now developing anti-glucosepane monoclonal antibodies to cleave unwanted cross-links. The collaboration between the Spiegel Lab and SRF dates all the way back to 2011, but it was in 2015 that the Lab announced its success and published a related paper [4] in the journal Science.

Further information on glucosepane cross-link breakers can be found in this interview with Dr. David Spiegel from Yale University on Fight Aging!; a list of studies on the subject funded or otherwise supported by the SRF is available here.

SRF also worked with the Babraham Institute on a cross-link quantification project.

Let’s help SRF move forward

Readers who wish to donate to SRF to help the organization in its crusade against the ill health of old age can do so by contributing to its winter fundraiser or even becoming SRF patrons. Have a look at SRF’s donation page to find out more.

NB: Dr. Aubrey de Grey (Chief Science Officer and Co-founder of SENS Research Foundation) himself held an AMA (“ask me anything”) on Reddit on December 7, at 14:00 PST (22:00 UTC, 17:00 EST). The questions and Dr. de Grey’s responses can be found here.

Literature

[1] Boominathan, A., Vanhoozer, S., Basisty, N., Powers, K., Crampton, A. L., Wang, X., … & O’Connor, M. S. (2016). Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant. Nucleic acids research, 44(19), 9342-9357.

[2] Gaspar, J., Mathieu, J., & Alvarez, P. (2016). A rapid platform to generate lipofuscin and screen therapeutic drugs for efficacy in lipofuscin removal. Materials, Methods and Technologies, 10, 1-9.

[3] Mathieu, J. M., Wang, F., Segatori, L., & Alvarez, P. J. (2012). Increased resistance to oxysterol cytotoxicity in fibroblasts transfected with a lysosomally targeted Chromobacterium oxidase. Biotechnology and bioengineering, 109(9), 2409-2415.

[4] Draghici, C., Wang, T., & Spiegel, D. A. (2015). Concise total synthesis of glucosepane. Science, 350(6258), 294-298.

 

About Steve Hill

As a scientific writer and a devoted advocate of healthy longevity technologies, Steve has provided the community with multiple educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity Reporter, Psychology Today, and Singularity Weblog. He is a co-author of the book Aging Prevention for All – a guide for the general public exploring evidence-based means to extend healthy life (in press).

About Nicola Bagalà

Nicola Bagalà has been an enthusiastic supporter and advocate of rejuvenation science since 2011. Although his preferred approach to treating age related diseases is Aubrey de Grey’s suggested SENS platform, he is very interested in any other potential approach as well. In 2015, he launched the blog Rejuvenaction to advocate for rejuvenation and to answer common concerns that generally come with the prospect of vastly extended healthy lifespans. Originally a mathematician graduated from Helsinki University, his scientific interests range from cosmology to AI, from drawing and writing to music, and he always complains he doesn’t have enough time to dedicate to all of them which is one of the reasons he’s into life extension. He’s also a computer programmer and web developer. All the years spent learning about the science of rejuvenation have sparked his interest in biology, in which he’s planning to get a university degree.

About LIFE EXTENSION ADVOCACY FOUNDATION (LEAF)

In 2014, the Life Extension Advocacy Foundation was established as a 501(c)(3) non-profit organization dedicated to promoting increased healthy human lifespan through fiscally sponsoring longevity research projects and raising awareness regarding the societal benefits of life extension. In 2015 they launched Lifespan.io, the first nonprofit crowdfunding platform focused on the biomedical research of aging.

They believe that this will enable the general public to influence the pace of research directly. To date they have successfully supported four research projects aimed at investigating different processes of aging and developing therapies to treat age-related diseases.

The LEAF team organizes educational events, takes part in different public and scientific conferences, and actively engages with the public on social media in order to help disseminate this crucial information. They initiate public dialogue aimed at regulatory improvement in the fields related to rejuvenation biotechnology.