Wake up people, it’s time to aim high!

Long interview with Dr Aubrey de Grey

Aubrey de Grey

Preface

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 cause pathology, the damage itself — the structural difference between old tissue and young tissue — is categorized and understood pretty well. By repairing damage and restoring previous undamaged — young — state of an organism we can really rejuvenate 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, 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

Ariel Feinerman: Hello, Dr Aubrey de Grey!

Aubrey de Grey: Hi — thanks for interviewing me.

Ariel 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 age reversal. 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: 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 retroviruses free pigs! In 2016 Juan Carlos Izpisua Belmonte has reprogrammed cells by using special factors and reverted back biological clock in live mice. And it’s only a tiny fraction of news!

Aubrey 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.

Ariel 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!

Aubrey 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.

Ariel Feinerman: You have really changed the world’s opinion, but now you are behind the scene. 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 how can it be fixed?

Aubrey 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.

Ariel 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?

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

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

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

“Ending Aging” revisited

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

Aubrey 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 short introduction to SENS research on their 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 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”.

Ariel 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!

Aubrey 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.

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

Aubrey 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.

Ariel Feinerman: How do you find useful bacteria?

Aubrey 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.

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

Aubrey 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.

Ariel 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 delivery problem can we be able to apply WILT?

Aubrey de Grey: Yes, certainly.

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

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

Ariel 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 a damage. But restoring previous epigenetic profile by special reprogramming factors we can turn old cell in the young cell, and resetting profile we can turn adult cell to pluripotent stem cell. Experiments show that restoring 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 SENS model, calling EpiSENS?

Aubrey 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 though no, epigenetic noise accumulates too slowly to matter, other than maybe for cancer (which, of course, we are addressing in other ways).

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

Aubrey 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.

Ariel 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 make apoptosis, become senescent or 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.

Aubrey 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.

Ariel 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 proposed Whole-body Induced Cell Turnover)?

Aubrey 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 year.

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.

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

Aubrey 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.

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

Aubrey 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.

Ariel Feinerman: Oh, can you unveil the mystery?

Aubrey 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.

Ariel 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?

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

Ariel 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 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.

Aubrey 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.

Ariel 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 of them are for very specific diseases and not for rejuvenation. Or will we get it as a side-effect?

Aubrey 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.

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

Aubrey 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.

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

Aubrey 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!

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

Aubrey 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.

Ariel 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 — more widespread form of intracellular junk.

Aubrey 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.

Ariel Feinerman: Now everyone is obsessed with “ageing biomarkers” and “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?

Aubrey 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

Ariel 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?

Aubrey 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.

Ariel Feinerman: Does SENS Research Foundation or associated companies hold regular meetings with 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 medicine uses completely different repair-based rather than compensatory approach and needs different clinical trials protocols and the whole new health paradigm. Transition period has already begun and we should use it wisely, otherwise US may become an outsider in the medical world.

Aubrey 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.

Ariel Feinerman: We already have many amazing results in the lab which can save human lives just now, but lack of funding and up-regulated medical system don’t give them any chance to be in clinics in coming years. With 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 when all 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.

Ariel Feinerman: The current WHO’s agenda is kind of shame! They know that 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. 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!

Aubrey 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

Ariel 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! Which 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?

Aubrey 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.

Ariel 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 SENS web page and read last years annual report.

Aubrey 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 is bad for you? How can this information may help us create a new cure against cancer, Alzheimer’s or atherosclerosis? Do we really need another one work 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! While we know 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 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 you 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.

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

Aubrey 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!

Ariel 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?

Aubrey 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.

Ariel 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 rise tens of millions dollars via ICO for clearly doubtful projects. While really important areas like generative medicine, rejuvenation biotechnology or bionics are permanently experiencing an acute thirst of money. Do you consider ICO for Project|21? I believe it perfectly fits into ICO conditions and requirements!

Aubrey 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

Ariel Feinerman: When I ask people, do they want to live hundreds of years? many of them say “no”, but when I ask them, do they want to look and feel like 30 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 regret about your claims about big numbers and 1000 years lifespan? People usually understand them in the wrong way. Some your colleagues say that without such claims your ideas would be much more popular.

Aubrey 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.

Ariel 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?

Aubrey 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.

Ariel Feinerman: Although, biomedical gerontologists do not afraid to speak about ageing any more, as it was 10 or even 5 years ago, which itself is a very big step, they are still very sceptical — at least publicly — about our ability to put ageing under medical control in a 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 nuclear fusion reaction they was excited by the idea to build a fusion reactor. Being full of courage they started to work and immediately came across many obstacles. Although reaction itself is very simple, the processes behind it are complex.

However, engineers haven’t given up and 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 can, 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, is it possible to build such a reactor? he answer: “Yes, of course!” And if you ask an engineer, when can we build it? he probably says: “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, can we defeat ageing, he likely calls you a crazy. Why? They are both engineering problems!

Aubrey 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.

Ariel Feinerman: Yeah. With current pace of progress anything beyond 2030 is 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 just now. So why do many [anti]ageing researches 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!

Aubrey 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.

Ariel Feinerman: Maybe, that is the reason? Maybe we need to have less 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.

Aubrey 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.

Ariel 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 to 2035 and grow new limbs to 2030. If it is not about life extension, so what is it all about? Why do they behave in such a manner? Because of pro-ageing trans? 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 the will be no progress in cell engineering. Each technology alone unlikely will be game changer but when combined their impact will be enormous!

Aubrey 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.

Ariel 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 human organism as premature ageing.

Aubrey de Grey: Thank you for your support!

Afterwords

We live in the exciting era, The Era of Very Rapid Progress in science and technology — era when many things which were merely a science fiction only five years ago are common now, and things that are no more than a science fiction now will be common in next five years. At the same time we live in The Era of Great Uncertainty — 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 (like it was in the case of glucosepane research).

New rejuvenation medicine is still very young and fragile like the first spring flower after 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 grey 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? No one 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 finish and “live long enough to live forever”. But he won’t! It is too big, too ambiguous project for one person. Now you know — your future 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 just 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 SENS Research Foundation and 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 a 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 is it 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 well-written plan, 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!