Aging rejuvenation is a thing – Fresh interview with Aubrey de Grey

What is aging? We can define aging 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 Aubrey de Grey, again! For those of you who are not familiar with him, here is a brief
introduction.

Dr Aubrey 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. He assigned $13 million of his inheritance to fund SENS research.

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-aging 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 Interview of Aubrey de Grey

Ariel Feinerman: Hello, Dr Aubrey de Grey!

Aubrey de Grey: Hello Ariel – thanks for the interview.

Ariel Feinerman: How do you feel 2018 year? Can you compare 2018 to 2017 or early years? What is changing?

Aubrey de Grey: 2018 was a fantastic year for rejuvenation biotechnology. The main thing that made it special was the explosive growth of the private-sector side of the field – the number of start up companies, the number of investors, and the scale of investment. Two companies, AgeX Therapeutics and Unity Biotechnology, went public with nine-digit valuations, and a bunch of others are not far behind. Of course this has only been possible because of all the great progress that has been made in the actual science, but one can never predict when that slow, steady progress will reach “critical mass”.

Ariel Feinerman: In 2017 SENS RF have received about $7 million. What has been accomplished in 2018?

Aubrey de Grey: We received almost all of that money right around the end of 2017, in the form of four cryptocurrency donations of $1 million or more, totalling about $6.5 million. We of course realised that this was a one-off windfall, so we didn’t spend it all at once! The main things we have done are to start a major new project at Albert Einstein College of Medicine, focused on stem cell therapy for Alzheimer’s, and to broaden our education initiative to include more senior people. See our website and newsletters for details.

Ariel Feinerman: What breakthroughs of 2018 can you name as the most important by your choice?

Aubrey de Grey: On the science side, well, regarding our funded work I guess I would choose our progress in getting mitochondrial genes to work when relocated to the nucleus. We published a groundbreaking progress report at the end of 2016, but to be honest I was not at all sure that we would be able to build quickly on it. I’m delighted to say that my caution was misplaced, and that we’ve continued to make great advances. The details will be submitted for publication very soon.

Ariel Feinerman: You say that many of rejuvenating therapies will work in clinical trials within five years. Giving that many of them are already working in clinical trials or even in clinic (like immunotherapies, cell and gene therapies) do you mean first – maybe incomplete – rejuvenation panel, when you speak on early 2020?

Aubrey de Grey: Yes, basically. SENS is a divide-and-conquer approach, so we can view it in three overlapping phases. The first phase is to get the basic concept accepted and moving. The second phase is to get the most challenging components moving. And the third phase is to combine the components. Phase 1 is pretty much done, as you say. Phase 2 is beginning, but it’s at an early stage. Phase 3 will probably not even properly begin for a few more years. That’s why I still think we only have about a 50% chance of getting to longevity escape velocity by 2035 or so.

Ariel Feinerman: Even now many investors are fearful of real regenerative medicine approach. For example pharmacological companies which use small molecules, like Unity Biotechnology, received more than $300 million, in much more favour than real bioengineering companies like Oisin Biotechnologies, received less than $4 million, even though biological approach much more powerful, cheap, effective and safe! Why in your opinion, and when can we see the shift?

Aubrey de Grey: I don’t see a problem there. The big change in mindset that was needed has already occurred: rejuvenation is a thing. It’s natural that small-molecule approaches to rejuvenation will lead the way, because that’s what pharma already knows how to do. Often, that approach will in due course be overtaken by more sophisticated approaches. Sometimes the small molecules will actually work well! It’s all good.

Ariel Feinerman: Do you agree, that small-molecule approach is generally wrong way in the future rejuvenation therapies? Because they have many flaws – especially their main mechanism via interference with human metabolism. Unlike them SENS bioengineering therapies are designed to be metabolically inert – because they just eliminate the key damage, they do not need to interfere with metabolism, so it is much easier than usual to avoid side effects and interactions with other therapies. They just eliminate the key damage, which means they are easier to develop and test – and much safer.

Aubrey de Grey: Ah, no, that’s too simplistic. It’s not true that small molecules always just “mess with metabolism” whereas genetic and enzymatic approaches eliminate damage. Small molecules that selectively kill senescent cells are absolutely an example of SENS-esque damage repair; the only thing against them is that it may be more difficult to eliminate side-effects, but that’s not because of their mode of action, it’s because of an additional action.

Ariel Feinerman: In recent years many countries show green light for regenerative medicine. Fast-track approval in Japan, for example, which allows for emerging treatments to be used so long as they have been proven safe. The similar approach works in Russia. What about EU or USA?

Aubrey de Grey: There’s definitely a long way to go, but the regulatory situation in the West is moving in the right direction. The TAME trial has led the way in articulating an approvable endpoint for clinical trials that is ageing in all but name, and the WHO has found a very well-judged way to incorporate ageing into its classification.

Ariel Feinerman: Do you think of working with USA Army? As far as we know they make research on regeneration and are very interested in keeping soldiers healthier for longer. Then they have much money!

Aubrey de Grey: The Department of Defense in the USA has certainly funded a lot of high-impact regenerative medicine research for many years. I’m sure they will continue to do so.

Ariel Feinerman: Is any progress in the OncoSENS programme? Have you found any ALT genes? Is any ongoing research in WILT?

Aubrey de Grey: No – in the end that program was not successful enough to continue with, so we stopped it. There is now more interest in ALT in other labs than there was, though, so I’m hopeful that progress will be made. But also, one reason why I felt that it was OK to stop was that cancer immunotherapy is doing so well now. I think there is a significant chance that we won’t need WILT after all, because we will really truly defeat cancer using the immune system.

Ariel Feinerman: Spiegel Lab has recently published an abstract where they say they have found 3 enzymes capable of breaking glucosepane. Very exiting info! When can we hear more on their research? Revel LLC is very secretive company.

Aubrey de Grey: They aren’t really being secretive, they are just setting up.

Ariel Feinerman: When can we see the first clinical trial of glucosepane breaker therapy?

Aubrey de Grey: I think two years is a reasonable estimate, but that’s a guess.

Ariel Feinerman: What do you think of the Open Source approach in rejuvenation biotechnology? Computer revolution in early 2000 has taken place only because Open Source caused an explosion in software engineering!

We have many examples when Big Pharma buys small company which has patents on technology and then cancel all research. In Open Source approach you cannot “close” any technology, while everyone can contribute, making protocol better and everyone can use that without any licence fee! Anyway, there are countries where you cannot protect your patents. Maybe there will be better to make technology open from the beginning?

Famous biohacker Josiah Zayner say: “In the gene therapy world most treatments are easy to replicate or pirate because you can reverse engineer the DNA from scientific papers or patents. Same exact treatment, same purity and quality I could give to someone rejected from the clinical trial. The cost? Hundreds or a few thousand dollars at most. Same deal with immunotherapy.”

Aubrey de Grey: I think you’ve pretty much answered your own question with that quote. The technologies that will drive rejuvenation are not so easy to suppress.

Ariel Feinerman: Are SENS RF going to begin new research programmes in 2019?

Aubrey de Grey: Sure! But we are still deciding which ones. We expect that our conference in Berlin (Undoing Aging, March 28-30) will bring some new opportunities to our attention.

Ariel Feinerman: What are your plans for 2019?

Aubrey de Grey: I’d like to say less travelling, but that doesn’t seem very likely at this point. Really my goal is just to keep on keeping on – to do all I can to maintain the growth of the field and the emerging industry.

Ariel Feinerman: Thank you very much for your answers, hope to see you again!

Aubrey de Grey: My pleasure!

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28 thoughts on “Aging rejuvenation is a thing – Fresh interview with Aubrey de Grey”

  1. Most flavanols are bitter. The chocolate ones are probably more of the same. Milk chocolate though…that is speaking my language.
    Unfortunately the way chocolate is processed most of the flavonols are destroyed. There are minimally processed chocolate nibs. Though, as you might guess, they are a bit bitter.
    I say swallow the pill and eat the milk chocolate or whatever chocolate you prefer.

    If pregnant or nursing, sadly all this stuff is a poor choice, as it is one of the most commonly lead tainted foods: https://www.asyousow.org/environmental-health/toxic-enforcement/toxic-chocolate

    And you can’t trust that the chocolate you bought doesn’t have it, because a test said it didn’t. The company could buy their chocolate from one farm one week then another…

    It also makes me concerned that could be some in the flavonol supplements. It that were true, I would just be shooing myself in the foot. I had forgotten about that concern.

    The lead is probably in the soil or early processing, or many companies would have no lead rather than the bulk of them having lead.

    Organic Cocoa Powder appears to have the most.

  2. Resistance is not an inevitable thing.
    Did you know that there are bees who have an antibiotic formula that they have used for thousands of years? They just use a combination of several compounds from a collection of bacteria to cure/prevent infection. And what mutates one direction makes it more vulnerable to something else. https://www.sciencedaily.com/releases/2014/09/140908093741.htm

    We need more antibiotics, and it is happening too.

    Someone developed a technique for keeping bacteria alive that generally die when you take them out of the dirt.

    There is a lot of stuff out there to discover and turn into antibiotics.

    Big pharmaceutical companies haven’t been trying. They don’t like cures, especially cheap ones.

    This is one of the huge problems with pharmaceutical giants. They avoid undermining their earnings on some drugs by developing better ones especially ones that cure when they ere just treating a chronic condition currently.

    And we defiantly have to prevent them from buying a small company working on a cure for something the big company already treats chronically.

  3. It is not the generally healthy people that make resistant strains. Even if they quit their course of treatment early, their immune system would finish off whatever was infecting…resistance would be futile 😉 So why should there be any limit on them. The resistant strains generated in people, generally come from people with compromised immune systems, from things like HIV, advanced health conditions, old age, or infancy. But then if you chose to do this to the sicker people you stand a very good chance of killing them.

    It is the hospital environment that is most likely to spread those infections. They need to do a much better job of cleaning everything after someone dies of an infection being treated. And keeping things from being spread person to person ward to ward.

    How many infections could be nipped in the bud, if you could just go to the pharmacy and get antibiotics at the first sign of infection? And those otherwise healthy people would be less like to spread it to the immune challenged as well…because they would not have it as long.
    I think pharmacists in combination with an AI doctor (that a pharmacist works with) should be able to get you antibiotics lickety-split. If you have other serious health issues, then just sent you to Emergency.
    It is not like people are going to snort amoxicillin to get high.
    The physician monopoly on the ability to prescribe is one of the most abusive aspects of our healthcare system.

    So sure, orthogonal, but relevant.

    cont.

  4. I agree with some of your points. They need a very simple, quick, blood test that says, not only what you have, but exactly its make up. This can be done. They can make cards with an array of microscopic tests. And they should have already gotten statistics on what-kills-what most successfully…with the minimum of side effects. But, I think that should be done in the pharmacy. Or worst case, you take the card home do the little poke or whatever and take the card back later that day or the next. They run it through their machine. It gives its top five choices with their cost, success rate, and likely side effects…and you pick. And the computer should be informed as well. It should take into consideration your other health conditions, vitals, apparent severity of your infection, your current prescriptions, known drug allergies, and your genome. None of this takes extreme AI or anything. Just ordinary programming.
    I think everyone should have their genome done exactly for this reason. And results should all be followed and put in the system. You only get so much from studies, even if there are a few thousand people. Why not have data on everyone who took a medication? You want to know ahead of time if you are one of the oddballs that is going to have an adverse reaction.
    I think you need all the antibiotic options available. What you are saying sounds great, but it is not needed and will cause needless suffering and deaths.

    cont.

  5. I’d say we’re much more likely to find intelligent aliens in the next 20 years than a cure for aging.

  6. Heh, it’s fun to play with, and strange things do happen.

    While I don’t believe it is impossible, physically, I don’t believe there is a significant likelihood we will be able to find any other intelligent life in this galaxy (i.e. builds tools and can maybe talk to us) even if we send a spaceship to every star in the Milky Way, but every time astronomers spot something neat, like Tabby’s Star, I rush to my web browser to see if maybe, just maybe, we beat the odds.

  7. I could see it going either way; If the treatments are expensive enough that people defer having children to pay for them, not using them might be selected for by evolution.

  8. What you’re talking about is orthogonal to my point. How hard it is to get antibiotics, vs which antibiotics are available at any given time.

    Scheduled rotation involves dividing antibiotics into groups based on the genetic basis of resistance to them, and then rotating through the groups, making the antibiotics which are “fallow” completely unavailable outside emergency situations. Thus encouraging bacteria to lose resistance to the next scheduled group.

    This doesn’t mean the antibiotics in the currently available group have to be tightly rationed.

    Though they should be more intelligently used. I get an infection, usually some form of bronchitis, (My lungs were damaged by an invasive lymphoma and the chemo that cured it.) go to urgent care. They don’t make the slightest effort to determine what I’m infected with, or what it’s vulnerable to, they just hand me a prescription for a Z pack, or whatever.

    My wife, who’s a third my weight, typically gets prescribed the same dose… The result is she gets ill from an overdose, and stops early. I run out before the infection is entirely gone, and it comes back resistant. Or maybe just shrugs it off, and it’s a week to 10 days before I get to try a different antibiotic.

    What they don’t do is culture my infection, and test it against a selection of antibiotics, and FIND OUT WHAT WOULD WORK. Instead of just guessing until I either get well or die.

  9. The people not using the antiaging treatments will select themselves out. And they will become irrelevant in 20-30 years…

  10. Most antibiotic resistance can be tracked to farm use. That needs to go way down. No prophylactic farm use. But on the human side, I strongly disagree. Even if you buy their claim that it is people discontinuing before completing their course of treatment, you have to look at why that is. We make it very hard to get the pills. You have to make an appointment. It is going to be inconvenient because you work when they do. You have to fill out all sorts of idiotic paperwork detailing if you have ever had a zit. You have to come in an hour before your appointment or they put even more people ahead of you. Then you wait in the doctor’s office for another 20 minutes for them. But he/she doesn’t give you the medication, he/she gives you a prescription…or they tell you it is now too severe and you need to go to emergency…where they make you wait 5 hours before they do anything more than give you a Band-aid. Insure that infection is really raging so they can milk the system for 3 days of IV drip.
    Now, if that is the case, and the antibiotic, Poof! saves your life…which is generally does, wouldn’t you hoard just a few pills instead of taking the whole treatment? That is what is happening. They make it hard, so people want to keep some because they know how hard it is to get.
    Stupid. The pharmacist can see that you got an animal bite, or a puncture, or whatever. But they can’t let you buy anything that will help. If it was easily, people would take the full treatment.

  11. We need to do more development work on phages to attack bacteria. They have a lot of potential to be free of nasty side effects such as this tinnitus an antibiotic gave me.

    Also, antibiotic management needs to be improved: In theory antibiotic resistance extinguishes rapidly once an antibiotic is out of use, meaning that we could cycle through a finite pool of antibiotics on a periodic basis, so long as each related antibiotic got enough of a period out of use for resistance to extinguish.

    At this point there isn’t enough regulation of antibiotic use, and as a libertarian that was NOT easy for me to say.

  12. I’m glad to hear they’ve dropped WILT. The concept of an anti-aging treatment that would cause you to die a relatively rapid and unpleasant death if you ever stopped it never made much sense to me: Anti-aging treatments should at least be walk-away safe.

  13. I’m not sure Aubrey is going to make it, himself, but a thousand years from now, those of us from today that are still around, should build him a nice memorial.

  14. Very legitimate comment, but still it’s hard to completely rule out the importance of maximum/soonest exposure (of genpop) to the notion and acceptance of aging as just another arbitrary/random parameter inherited from our origins rather than an actual universal constant or divine obligation or natural law or whatever.

    There’s enough margin to have both approaches beyond both of their current investment levels.

  15. One thing they tend to ignore: We accumulate latent infections over time during our lives which contribute and likely accelerate health decline. They act like HIV, only not as quick…requiring the immune system to stay on top of the infections. Most of these are viral. The immune system is not particularly good at fighting infections in the nervous system, in fat, or in cartilage. And many antibiotics can’t reach cartilage or kill bacteria that have a slimy protective coat like gingivitis and other nasties: https://www.livescience.com/46465-bacteria-in-arteries-may-be-ticking-time-bombs-researchers-say.html. And of course antibiotics can’t do a thing about viruses except maybe reduce the work an immune system is trying to do by killing a bacteria that you may also have. I do think we are beginning to enter a phase where broad-spectrum antivirals will be developed. This is a very important story that has been missed by a lot of people: https://medicalxpress.com/news/2019-01-hong-kong-scientists-broad-spectrum-antiviral.html
    And there is DRACO which unfortunately seems to be stagnating, though it has immense promise. https://riderinstitute.org/pages/draco
    And the immune system amplifiers they are using to fight cancer may also come into play. And there are other things beyond bacteria and viruses. Odds are you have this bug roaming around in your brain feasting on who knows what: https://en.wikipedia.org/wiki/Toxoplasmosis
    There is a cure…that drug Shkreli price gouged.

  16. Yes, even if all it does is help people live healthy lives to 100 it would be a game changer for individuals and for society at large. To have an average 20 extra years with all the accumulated knowledge and wisdom that older people have would be increasing their lifetime contribution to progress and society by two fold.

  17. Oh, I guarintee there will be people who will not hop onboard. But large numbers will…certainly. And there are people who only want increased healthspan and don’t want to live way over 100 years. Will they change their minds? Quite possible.

  18. There are some things that can help skin now. Topical Epidermal growth factor (EGF) products appear to work to some degree. And cocoa flavanols taken internally appear to work to some degree.
    But I haven’t bought ether. If I were a woman, I probably would have. Still considering the cocoa flavanols because what helps the skin, often helps the brain as they derive from the same tissue during development.
    Of course, a good glucosepane breaking enzyme would be fantastic for lots of reasons. And as glucosepane causes some externally visible damage of aging, correcting that should be a massive market. Though glucosepane does a lot of internal damage as well.

    What would really be cool is genetic modification inserting genes to make the enzyme or enzymes that eliminate glucosepane into our cells to make the stuff as needed, so we never accumulate the stuff in the first place.

    People may be slightly disappointed in a glucosepane remover if they are looking strictly for visual improvement. There are a lot of crosslinks that are just collagen and elastin crosslinks involved in wrinkles. Those crosslinks are mostly limited to the skin where there was a lot of sun damage. You have to breakup all of this to remove wrinkles. Not sure how the cocoa flavanols work, but the EGF stimulates cell division.

    The body already makes enzymes to break up and recycle collagen and elastin. Perhaps that can be stimulated in some way. However, this could be very dangerous causing arthritis.

  19. Once some people start looking and testing younger (real metrics) EVERYONE will get on the train. Even those that poo poo it. Do you want more life? No. No. I have had plenty. Not. Gonna. Happen.

  20. Is it better to lose 5 years in SENS research today and speed up 100 times the research later because we can apply AI to it? You decide, because your preferences and needs are not mine.

    Is it better to research AI today and reduce car crashes, allowing autonomous cars to be developed, less people to die, less wealth needed to replace cars and take care of wounded and maimed, more people continuing to create wealth instead of using or not producing it.

    Just think the researchers using self-driving cars can study or rest when traveling and not use their time to drive a piece of metal, be more rested for the real useful task , etc. And part of the wealth and resources liberated from car crashes outcomes can be redirected to research.

  21. There are many reasons a lot of money is not put in SENS research

    1) lack of understanding of the technology
    2) short-term greed (there is no business plan to profit from it).
    3) people like Jeff Bezos want to give money (for profit or not) to people able to deliver. If they don’t find a person with the right skills, no money.
    4) People like Bezos have very little free time, so they narrowly select their interests
    5) Not always single big investments are a good thing in the long term. It is better if there are a lot of small groups researching their own things independently and then we see who is right, who is wrong, etc. Then the successful research get more money.
    6) One of the most important thing to accept is unforesaw development come from unrelated fields very often. Investments in AI could not advance SENS research today, but they lower the long term costs of researching SENS and increase the speed of SENS research with time.

  22. If those glucosepane breaking enzymes turn out to make aged skin look younger, Revel LLC will be worth a fortune.

  23. Feinerman asks: “We have many examples when Big Pharma buys small company which has patents on technology and then cancel(s) all research. In Open Source approach you cannot “close” any technology, while everyone can contribute, making protocol better and everyone can use that without any licence fee! Anyway, there are countries where you cannot protect your patents. Maybe there will be better to make technology open from the beginning?”
    de Grey say the technology is not so easy to suppress, but it seems it is. Where is ANY open source life-extension (LE) tech? Why do Big Pharma companies fight with everything they’ve got to extend patents & do trivial enhancements to restart the clock, even delaying those enhancements until they are just about to run out the original patent? The answer is: profits, not useful medicine. This is why we don’t see any useful LE treatments so far. That and ridiculously low amounts of money in the field (de Grey should not have to use the bulk of a small inheritance – by Pharma standards – just to keep his SENS institute alive a few more years).
    There’s also a built-in Religiopharma bias against LE research, which doesn’t apply to disease-cure research.

  24. That is one interpretation. The other possibility was that he was sending the flood in 120 years from the date of that statement. It fits better too, as there were several people who lived far longer well after that statement. Abraham, for example, lived for 175 years.
    It is kinda cool coincidence that the modern limit appears to be about 120 years. There is considerable doubt that the 122 lady actually lived that long. She may have pretended to be her mother to avoid taxes during inheritance. Though that is far from proven at this point. One thing going for her, is that she never heated her house. And so she was often very cold. And if her body failed to keep her internally at 98 ish degrees, then her reduced body temperature may have extended her life. At one point she had to be treated for frostbite.
    The next oldest was 119 and 97 days. They analyzed her body. Her cardiovascular system was fine as was her brain. I think her immune system ran out of stem cells. Though, I can’t find the article about the autopsy.

  25. Imagine what could be done if the world’s top billionares all threw a few hundred million into the field. Bezos alone could donate billions.. hell his ex wife just walked away with 35billion. I just don’t understand why so few people are willing to put all that wealth to work on AI, medicine, nano-tech, longevity etc. I’m not talking about classic charities like feeding poor Africans, I mean research that will take us into the future.

    A one time 5 billion dollar pool of money dispersed out to 100 different research firms and teams in the form of grants and prizes could change the field – and the course of human history- within a very short amount of time.

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