Recently, Avi Roy, alongside Nathan Cheng & Laura Minquini, hosted the second Longevity Panel discussion, which assembled some of the brightest minds working on reversing aging, and enhancing health and life span.
As with the first event, this discussion was intended to illuminate how they are approaching longevity and to know if we are any closer in achieving it.
The talk was split into two sections: the first being open discussion guided by questions from the hosts. The talk was then opened up to the floor, allowing audience questions. Part 1 will provide the transcript from the first section of the Longevity Panel. Enjoy!
George Church – George is the Robert Winthrop Professor of Genetics at Harvard Medical School, Professor of Health Sciences and Technology at Harvard and MIT, and a founding member of the Wyss Institute for Biologically Inspired Engineering.
Nir Barzilai – Nir is the director of the Institute for Aging Research at the Albert Einstein College of Medicine and the Director of the Paul F. Glenn Center for the Biology of Human Aging Research and of the National Institutes of Health’s Nathan Shock Centers of Excellence in the Basic Biology of Aging.
Jim Mellon – Jim is the co-founder and Chairman of Juvenescence, a company which aims to develop science-backed therapies that extend both healthspan and lifespan. Jim has also established the Mellon Longevity Science Programme at Oxford.
Jay Olshansky – Jay is currently a Professor in the School of Public Health at the University of Illinois at Chicago, Research Associate at the Center on Aging at the University of Chicago, and co-founder & Chief Scientist at Lapetus Solutions, Inc.
Alejandro Ocampo – Alejandro is Assistant Professor at the University of Lausanne. His research areas include epigenetics, stem cells, aging and mitochondrial diseases with the goal of clarifying disease mechanisms and developing novel therapeutic approaches to improve the quality of life of patients.
Kristen Fortney – Kristen is the CEO and co-founder of BIOAGE. A clinical-stage biotechnology company on a mission to develop a broad pipeline of therapies that target aging in order to increase healthspan and address chronic diseases.
(The timestamps relates to when the question in asked in the full video)
00:40 – Have you ever considered that it’s possible that we’re looking at the wrong side of the equation when looking at aging in general. The metaphor I’m going to use here is: if we were trying to figure out how to fly, you wouldn’t look at all the creatures that don’t fly and try to figure out like how to fly based on that. You’d be looking at things that fly. So do you think that maybe we should be looking at regeneration as the trait rather than aging as the trait? Or have you considered that possibility?
04:06 – Do you guys think that there’s enough evidence that aging is modifiable at this point? Or do you think, there’s going to have to be additional big milestones in the lab before a majority of people are able to be convinced that aging is modifiable?
07:06 – Nanotechnology – if it was available, would it be possible to target certain things in the body at a cellular level to reverse aging?
09:08 – What obstacles they’re facing in their research that might delay or prevent progress?
10:46 – George Church – In the end of June, Intellia Therapeutics announced that they’re going into human trials. Can you tell us some more about this approach?
13:03 – Senolytics – Is it better to remove senescent cells which will not be replaced by the body? Or is it better to just leave the senescent cells?
15:33 – Is there anyone using enzyme therapies as a senolytic drug or anyone thinking this could be a future therapy?
16:18 – Has there been any research done on hibernation and whether it would be an effective intervention for ageing or battle wounds?
18:03 – What has not been mentioned today, which you are most excited about in the longevity or the tackling aging field?
19:35 – Do we really need a kind of step change in our understanding of biology before we could really get to the bottom of ageing?
Here’s what was said:
Audience: Have you ever considered that it’s possible that we’re looking at the wrong side of the equation when looking at aging in general. The metaphor I’m going to use here is: if we were trying to figure out how to fly, you wouldn’t look at all the creatures that don’t fly and try to figure out like how to fly based on that. You’d be looking at things that fly. So do you think that maybe we should be looking at regeneration as the trait rather than aging as the trait? Or have you considered that possibility?
George Church: Oh I’ll take that. In a certain sense, we were looking at both, we’re looking at extremely long lived individuals, we’re looking at animals like bowhead whale, and we’re also looking at bonafide cases of aging reversal. So as you say, the, the animals with wings would, the equivalent would be things like reversing the state of a cell from say an 80 year old human cell to a nearly embryonic one. That’s an extreme case that kind of proves a point that you can really go a long distance in epigenetic space in reversing as many cell-based phenotypes as we’ve examined so far. But good question. Thank you.
Avi Roy: Alejandro or Kristen or Nir or Jim, anybody else want to take that question?
Alejandro Ocampo: I would actually like to add into that one. I think clearly with the reprogramming, just like you said in vitro, we can basically reverse the age of cell back to an embryonic state, but even if we want to go farther and he will look in nature that’s basically what a fertilization and reproduction does now.
You’re combining oocytes and eggs from individuals from a certain age, and you generate a new individual that will have a normal life as of, so I think even reprogramming is already trying to mimic a natural process that of course happens everyday
Kristen Fortney: And just super briefly, there are some animals out there that are like us, mammals that live hundreds of years, like bowhead whales.
So there are some efforts scientific efforts to try to figure out what’s different, and if we can copy some of their secrets, but I think it’s still early days and it’s challenging.
Audience: Okay. As an add on, do you guys think that germ cells are ageless?
Alejandro Ocampo: I will say, no, they are still aged and this is why they don’t have the same reproductive capacity, the oocytes from a 20 year old versus a 14 year old is definitely not the same. So I would say yes, they are still age. Yes.
Avi Roy: Thank you, Alejandro. And Nir, unless you have somebody else or something else to add maybe we can go to the next part.
Nir Barzilai: I’ll just say that to pick on the last comment, we can measure the aging of over ovaries and testes, but when a sperm fertilize an egg and the baby’s develop, then there is an erasement of age there. And that’s why we’re so optimistic that we have figured out naturally how to do something like that.
So, how can we do it in a whole body, and when it’s post-development.
Thanks, Aaron. Thanks Nir. Michael you’re up next, if you want to ask your question.
Audience: Thanks Avi. Great panel Laura, Nathan. Great combo everyone. Do you guys think that there’s enough evidence that aging is modifiable at this point? Convincing a majority of society is just a matter of more time and more propaganda, or do you think, there’s going to have to be additional big milestones in the lab before a majority of people are able to be convinced that aging is modifiable.
Nir Barzilai: I can start it by saying that, first of all, there’s no doubt that we have overwhelming data that ageing is modifiable. The extent of the data is impressive.
And part of the reason that people don’t understand it is, for example if you’re in cancer, curing cancer, this is a really hard task because every cancer has its own genome that is different than the genome of the other guy who has the cancer, and it’s different than any cancers like that in the world.
So you have to be very personalized in doing that. Ageing is really conserved through evolution. Okay. And that means that everybody kind of ages the same way, the skin, the hair, the skeleton, the diseases, the cancer, they are different, but the diseases are the same. And that is why some of the drugs and some of the interventions that we’re giving are working in all animals.
So I think really the idea of targeting ageing not only has been proven, it’s simpler than some of the tasks of dealing with diseases that are already there, whether it’s cancer or sarcopenia, frailty, it’s too late for that. So I think we have enough data. It’s more of our marketing publicity and people believing that this is here now.
Laura Minquini: Thank you Nir. Kristen has to jump off soon, so maybe she can answer before leaving and thank you again for being here with us.
Kristen Fortney: Oh, sure. Yeah just a last comment and thanks for a great panel guys. But yeah, I think the right kind of marketing could go a long way. I think there’s too much focus on the sort of sensationalist stuff, but in some ways for the people off aging.
So focusing on the real science and the real developments, I think that. That said, if we actually had something working, in a human, if someone got their hair back even, I think that package would make it even more compelling. But as people mentioned earlier that the field has been so chronically underfunded that even straight forward approaches t o get the word out there.
I think we could make a big difference. Yeah. Okay, I got to hop off now. Thank you guys.
Nathan Cheng: Thank you.
Laura Minquini: Thank you again for being here. We’re going to go to our next question, Pat, please go ahead.
Audience: I was just wondering, I was always curious if nanotechnology, if it was available would it be possible to target certain things in the body at a cellular level to reverse aging? If there was the availability of nanotechnology, like tiny robots that you breathe in which go through your body and repair cells or something along those lines. If the technology is being worked on or if it’s too far away from even being available.
George Church: This is George, Pat, I published on nanorobots that were biologically inspired. And I would say that the nanotechnology that works, that has been working in is likely to continue to be appropriate for this task, at least is bio-nanotechnology. And biology is already amazing. It can make things that are atomically precise at scale in the catalytic core of bio-nanomachines a fraction of an angstrom, a fraction of an atomic bond matters to the catalytic rate and that can be finessed, not just through ancient evolution, but through modern machine learning and accelerated evolution through how to parallel synthesis. So I think your intuition that nano devices is good. I think the most effective ones now, and probably for quite a while will be bio nano. BioNano is not necessarily limited in the periodic table. A huge fraction of the periodic table can, has been incorporated into either natural or synthetic biology. So I think that’s where we’re going to see a lot of progress that you can call nano technology if you’d like.
Laura Minquini: Thank you, George. We’re gonna move on to our next question and thanks for your question. Pat it was great.
Audience: My name’s Eden. Thanks for taking my question. I like to ask the scientists what obstacle, what obstacles they’re facing in their research that might delay or prevent progress? Thank you.
Laura Minquini: Alejandro or Nir, do you want to take this, or Jim, as an investor, you’re also welcome to say something. And I think you mentioned that a very suddenly it’s the lack of funding.
Jim Mellon: Just to underline that, I think that’s the key. And so everyone needs to, on this call, needs to try and find ways of getting people interested in this sector.
Alejandro Ocampo: Yes, I think I agree. A hundred percent funding is key, but I think large funding I think is coming, but more will come. In the moment we provide the first human data. Connecting to the question before, we have good data in models that we can slow our ageing, I’m not sure that it was reversing, but at least that we can slow down aging.
I think in the moment we have human data and then things will change significantly. Even if it’s with a simple drug, with whatever, just showing human data that aging can be modified. And I think even there a point that George mentioned from before, I think pets, whether it’s cats or dogs, they are going to play also a fundamental role in convincing people that you can really extend health span and lifespan, because this will be much quicker.
Laura Minquini: Yes, especially with millennials having less children, dogs take over that space. They’re like family, it’s a huge industry as well, pet care and accessories and all of that. With that said thank you for your question, Eden. Masha, welcome to the stage and thanks for being here.
Audience: Oh, hi everyone. I’m Masha, I’m a asset manager and thank you for having this great panel. Thank you for time for knowledge. And my question will be to George Church about one of his companies, which he is on the board, about Intellia Therapeutics. In the end of June, the company announced that they’re going into human trials. And I want to ask you if you can tell us some more about this approach?
George Church: Jennifer (Doudna) and I had been involved in Intellia and in Editas, and CRISPR therapeutics, are three siblings that are all within a few blocks of each other and Cambridge, Massachusetts.
And I think they get along pretty well, overall, and have divided up the landscape for both rare genetic diseases, as well as more common ones, including infectious diseases. None of them are working on the most common, one of all, which is the topic of this conversation, which is slowing down or reversing diseases of aging.
But yes, some of those, not just the CRISPR based therapies, but also gene therapies in general are really undergoing an explosion of success and investment. And this is partly because of the orphan drug act, makes that possible. But I also look forward to these powerful technologies being applied to more common diseases.
And I think part of the problem is it’s easier to get approval for devastating diseases, especially devastating, rare diseases is easier to get the approval process to work right now. But as soon as you show a few of those and and that’s already been done for editing and gene therapy for sickle cell and for retinal diseases, for example.
Laura Minquini: Thank you, George, and Masha for your question.
We’re going to go now to reign hold, please go ahead and ask your question.
Audience: Thank you, Laura. Thank you for organizing this amazing room. We should have more like this one. My question relates to senolytics. There’s been a lot of promising data on preclinical animal models. Mostly showing the benefits, the potential benefits of using different various senolytics.
And now we are starting to move into clinical trials. So testing these in humans. Now my question is, and sometimes when you hear companies has been out talking about senolytics, it is almost a fight of whose senolytics is most potent and most recent. My question leads to the potential toxic effects that they have. When we use them in the lab, they are certainly very effective and when we work with endothelial cells and they are senescent, they can get wiped out 80-90%. So they do work. My question relates to what happens if you don’t have cells to replace those. So let’s put an example, if you have an aged brain, and you have a few neurons there so are you better off with keeping your own neurons than wiping them out than having none? So that’s my question.
Nir Barzilai: Thank you. I can take it maybe. And you’re obviously, a little bit more in senolytics, but let me explain something. Senescence is a protective mechanism. If something goes wrong with your cell they might become an origin of cancer. If you don’t eliminate them by senescence or by apoptosis, there are several mechanisms.
The problem is that they accumulate. And when they accumulate, they have a biology that has to do with secreting proteins and other things. And this biology accelerates aging. So you need to remove those cells, but you certainly cannot stop the process of senescence because it is a protective mechanism.
Look what happens out there, is we know it happens everywhere. 95% of our drugs are failing. That’s why Jim is saying he’s investing in 20 companies. But senescence is a mechanism that is relevant to human and it’ll take time, maybe sooner rather than later, to have a better and better drugs.
Laura Minquini: Thank you, Nir. I believe that you do have to leave soon, so we’re gonna ask everybody to be very clear with their questions. So we try to get everybody to get to answer to ask Dr. Gould. Welcome to the stage, please. Go ahead.
Audience: Thank you. Hi everyone. My question was to Mr. Mellon, but I think he left. And my question is about the senolytics. Is there anyone using enzyme therapies as a senolytic drug or anyone thinking this could be a future therapy?
Alejandro Ocampo: I’m not an expert in the field, but I think people are trying a lot of different strategies. I didn’t hear before about the enzymes, but the company that comes to my mind is of course, One Skin, that is using a peptide to eliminate senescent cells in the skin. But not enzymes that I know of.
Laura Minquini: Thank you, Alejandro. John, you’re up next.
Audience: In terms of market sizes, I think every year we spend about a half a trillion dollars on injury, and relating that to ageing has anyone, or what’s the state of kind of hibernation, so slowing down the aging process so that you can buy yourself time to, find a cure or treat a battlefield wound.
Nir Barzilai: I don’t think there’s really application that I know of that. It’s believed that caloric restriction that extends life in animals by 40%, that the metabolic rate is reduced. But in fact, you have to look at it not as the whole animal, but per gram of muscle or any active tissue. And I’m not sure that we’re convinced that just changing metabolism is going to extend the lifespan. I don’t see it as any company, any of the biotechs we’re thinking about this approach.
George Church: I think that slowing things down is great for trauma, where you can spiral out of control into multiorgan failure and in ours, but aging is typically a much longer deal. Slowing down one’s life for decades is not really a great option. I think we should all think out of the box as much as possible. So let’s use that as inspiration.
Audience: I think slowing down my body’s aging would be interesting. My mind still goes full speed on the internet, but I guess I’m thinking more from that perspective is there a separation between mind and body there with the hibernation?
Laura Minquini: We’ll probably have to do another series exploring that. Thank you, John and George and Nir for answering those questions. Chris, you’re next.
Chris Curwen: Hi guys. I just wanted to say thank you so much for the panelists and all the hosts for this, a fantastic talk. My question is what has not been mentioned today, which you are most excited about in the longevity or the tackling aging field?
George Church: I think we’ve done a pretty good job of covering the landscape. There definitely deeper dives that we could take on each of these topics. There’s the whole issue of systems biology integration that we’ve touched upon where you might have to get a bunch of things right at once.
There’s the issue of delivery. I think that’s something, no matter how you deliver, whether its a small molecule or a cell therapy or anything in between you do have to deal with delivering, not too much off target and so forth, but these are more deeper dives into things that we have touched on.
Nir Barzilai: Yeah, and I totally agree with it. I think, except on thinking of regeneration, that is really complex. I don’t think we have a technological obstacle. A lot of those things can be developed in the next few years. So from a technological problem, except as I said, except regeneration or regeneration of the brain is just impossible to think about even, but otherwise it’s not the technology that holds us it’s other things.
Laura Minquini: David, you’re the last question of the afternoon, please go on.
Audience: Hi, everyone. Thanks very much for letting me speak. It’s been really interesting. I had the kind of broad question. It was great to hear worms being mentioned, but it’s about basic biology. We still need to understand a lot more about the basic biology.
For example, in the Ecoli, about third of the genes we don’t know the function of. If we really want to understand how an organism ages, do we just need to know a lot more about the biology? Is it really, as Jim was saying with the much more investment, do we really need a kind of step change in our understanding of biology before we could really get to the bottom of aging. That’s what my question is.
Nir Barzilai: I wanna maybe start by making it some somewhat simpler. You’re saying ‘look, I know I have examples aging is really complex’, and we don’t argue with it. What we say though, is that they’re like upstream mechanisms, a lot of them we know, and a lot of them we will discover, that can be targeting the whole phenotype that you see of ageing. What we miss in the describing of aging and a lot of them, and they can be targeted. So I don’t want you to be like so much ‘we don’t know’, I think we know a lot of the important things.
George Church: I would add that In order to tackle E.coli we don’t need to know the remaining 50%. I work on E.coli among other things and antibiotics and of vaccines are working quite well without a complete knowledge. We have to be careful not to let complete knowledge to the perfection of science interfere with engineering. For example, our knowledge of both virology and immunology were not only primitive, they were non-existent when we started developing smallpox vaccines back in the 1500s and 1700s. And even by the time smallpox was eliminated, we still had very primitive knowledge of virology and immunology. I’m not advocating ignorance. I’m just saying that don’t let perfection interfere with engineering. The engineering you can work with a fairly limited pallet and still come up with amazing outcomes.
Guest: I’m not disagreeing with that in the way we’re doing it in a slightly empirical way. That’s how we found a lot of antibiotics and other things. And yes, we will find some great things that way, but I was just wondering if we need that much more understanding to really get to grips with aging that’s that was my question.
George Church: Yeah I think we will get tons of understanding, partly because we’re in an exponential phase. Even though Nir says we don’t need more technology, we are getting more technology, and it’s bringing the costs down it bringing the knowledge up. So we will have it, but it’s not just trial and error. And it’s also engineering. You can engineer with a very limited number of parts and make some amazing devices.
Nir Barzilai: George, I didn’t mean to say with only technology, I meant that we could make progress with the technology that we have that we should do now and it’s not stopping us. I certainly hope that technology will help us.
George Church: I agree. Yeah. I get your point.
Laura Minquini: Alejandro, do you want to say something as well?
Alejandro Ocampo: Yeah, I would like to add something. It’s true, one of the questions I think was going to be, if we know enough, if we have enough knowledge, I think we’d have some, but we could always learn more. And I think we need to take both a rational and irrational approach. Now we need to have a rational approach based on what we know and then try sometimes random things. We gain something, we learn more and we try again something again.
I think it needs to be a balance between the two, I completely agree there. Knowledge, technology and they will both feed each other in order to keep it to keep going.
We would like to say a huge thank you to all of the panelists for giving us a portion of their busy schedules, and providing such an enlightening and thoroughly fascinating conversation. Our thanks also goes out to the hosts who cultivated such a fantastic discussion!
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