Over the last 150 years, our life expectancy has grown, from 40 years in 1850 to over 90 years today in some countries. This can be attributed to advances in medical science, improvements in public health, and equitable access to healthcare, especially for maternal and infant care.
What will the future hold for our world? Will we be overwhelmed by a ‘silver tsunami’ of retirees with poor health, or will we use the latest research findings to rejuvenate the elderly and extend their lifespan?
Our Longevity Futures is a show where I, Chris Curwen, speak to scientists, engineers, entrepreneurs, doctors, politicians, and community activists who are giving the world the hope that we can all live longer and better, and improve our health.
In today’s episode of Our Longevity Futures, we are delighted to host Professor Matt Kaeberlein. Matt is a Professor of Laboratory Medicine and Pathology at the University of Washington School of Medicine. His research focuses on the basic mechanisms of aging in order to facilitate translational interventions that promote healthspan and improve quality of life.
Matt is also a co-director of the Dog Aging Project, in Washington, a long-term study committed to advancing our understanding of ageing and to accelerating medical breakthroughs for both dogs and humans.
Here are some of the highlights for my conversation with Matt:
Chris: Can you tell us a bit about your background and how you got interested in the field of longevity?
Matt: It was an accident, to be honest with you. I went to graduate school at MIT, thinking I was going to do structural biology or x-ray crystallography or something like that. My undergraduate training was in biochemistry and mathematics, so very biophysical. And I heard a talk by Lenny Guarante, who I ended up doing a PhD thesis with during my first semester at MIT, where he talked about how his lab was using genetics and molecular biology and biochemistry to study the biological ageing process, that it was in yeast at the time.
And still, to this day, I don’t exactly know what it was about that just captured my interest and enthusiasm, but I just really got turned on by the idea that you could scientifically study something as complicated as the biological ageing process.
Now, as I said, that was in yeast and, looking back to be completely honest, I have to admit at the time, I didn’t even care whether what we were studying was going to be relevant for human ageing. I just thought it was such a cool and complicated biological problem that I wanted to dive into it. That aspect of my view of ageing has changed over the years where now I’m very much interested in what we can learn about human ageing, but I think it was really just the complexity and the challenge, and the fact that I recognised even at that time, that ageing is really one of the unsolved mysteries of biology. And so to be able to have the potential to have an impact there, I thought would be really cool.
Chris: You are co-director of the Dog Aging Project. Can you tell us a bit more about what it is and how the project was started?
Matt: So the dog aging project really at its core is about trying to understand the biology of ageing in companion dogs or pet dogs. And there’s really two parts to it: 1. Is a large scale longitudinal study of ageing, it’s completely observational. And the goal there is to really identify the most important genetic and environmental factors that influence healthy ageing in companion dogs. The second piece of that is to actually try to impact the biology of ageing in companion dogs, through clinical trials, testing interventions that we think, based on laboratory studies, might actually slow ageing or in some cases reverse aspects of ageing. And so right now we have one clinical trial, it’s a clinical trial of a drug called rapamycin.
I think my vision for the future is that our studies won’t be limited to rapamycin. And in fact, the goal there is actually to have an impact on ageing in pet dogs. I think, what fundamentally differentiates the dog aging project from most of the nonhuman research in the field is the fact that these are actual companion animals living in the real world, other than studies that are carried out in humans, there really aren’t any studies in the field that experience ageing in the real world. And so I think that’s one, unique aspect to the dog aging project, that from a scientific perspective is really important.
Chris: It is well known that typically smaller dogs outlive larger dogs, why is this?
Matt: So before I jump into that point, this raises a sort of even more fundamental point that I want to make. Another reason why I really liked the dog aging project is I think that dogs in particular are a really powerful animal to illustrate the idea of biological aging to the general public. I still think most people, if you just walk up to somebody on the street and you start talking to them about the biology of aging, they’re gonna have no clue what you’re talking about. And I think dogs are a really useful example that people understand. We’ve all understood since we were kids this idea that one human year is about seven dog years, it’s not perfect, but it’s pretty close. And if you just explain to people what that means, right? Another way of saying that is dogs age about seven times faster than we do, than humans do. And so that tells you immediately that there’s something about the biology of dogs that’s different from people that, that regulates that rate of aging. And so if we can understand that biology, we have the potential to actually have an impact on that biology to modify the rate of aging.
So I really liked dogs for that reason because this idea of human years and dog years is exactly what we all talk about in this field all the time: that aging is biology, it can be modified. We just to have ways to communicate that to the general public. And I think dogs are a really great example of that.
So that wasn’t what you asked, but I wanted to share that because I think it’s a really powerful sort of message to get across.
So you asked, ‘why is it the big dogs seem to age faster than small dogs?’ So certainly big dogs have shorter lifespans or life expectancies than small dogs. That’s well-established and it seems they are aging biologically more rapidly than small dogs are. You can see that, based on functional declines, so changes in heart function or arthritis or kidney function are all accelerated in big dogs. They also have higher risk of cancer pretty much at every age, chronological age, a big dog has a higher risk of almost all forms of cancer that a small dog does.
So it seems like biologically they’re aging more rapidly. And I think we have to be honest, we don’t know with certainty why that is, but there’s a very plausible hypothesis that is suggested based on the genetics of body size in dogs. So the most important genetic variant for effecting body size in dogs is in the IGF-1 pathway insulin like growth factor, one pathway.
Elaine Ostrander showed this many years ago in a very nice paper published in Science. So if you have a variant that in the increases IGF one signalling, you get bigger dog, and of course bigger dogs are shorter lived. Now, why that’s interesting is we’ve learned from laboratory studies in mice and flies and C elegan worms that mutations in the IGF-1 like signalling pathway that reduced signalling also increased lifespan, so that the directional arrows are the same in C. elegans and fruit flies and mice and companion dogs that mutations that reduce IGF-1 signalling are associated and causal, at least in the laboratory animals, for longer lifespan.
So it’s a very plausible hypothesis. I think that the same thing is accounting for differences in life expectancy associated with body size in dogs. Again, I’m a little bit careful to say that it hasn’t been proven, cause nobody’s obviously done the experiment where somehow maybe with CRISPR change IGF-1 signalling in a big dog and see whether you affect lifespan. But I think that it’s pretty likely that’s the mechanism that’s underlying
Jared: Wolves are much longer lived than dogs, however they are a similar size, if not bigger than most dogs. Why is this?
Matt: So I’m not sure it’s actually the case that wolves are substantially longer-lived than companion dogs. It’s a little bit challenging, right? Because wolves of course, are in a different environment and anytime you’re in the natural environment for an animal, usually lifespans are actually depressed, because of things like predation, or if an animal gets injured, it’s unlikely to survive the next winter, things like that. First of all, that would be the first thing I would say.
I would also say it’s complicated. So companion dogs. While they have many powerful features for studying things like ageing or other aspects of biology. They’re also a little bit unique, right? In the sense, particularly if you look in purebred dogs are obviously relatively inbred, and so there is a depression in life expectancy that goes along with being purebred. If you just matched a body size, pure bred vs mixed breed, probably because of that inbreeding factor. At a given weight, it’s about a year difference in life expectancy, just because presumably of that inbreeding factor.
So it’s a little bit hard, I think, to draw, really apples to apples comparisons there, but I’m honestly not familiar with the data that’s suggests with any level of certainty that if you took a wolf, or enough wolves in captivity, and did a side-by-side sort of lifespan normalised the body size that the wolves would live substantially less.
Chris: We have successfully studied and shifted the rate of ageing in a number of trials in model organisms, namely; yeast, worms, flies, mice etc. How is the Dog Aging project different from these investigations?
Matt: I already talked about the fact that in the dog aging project, these are companion dogs living with their owners in the real world. So that is arguably the biggest difference between, the studies that have happened in yeast and worms and flies and mice, those are all in the laboratory. And of course in the laboratory we are typically maintaining these animals in a highly controlled environment, it’s relatively sterile compared to the real world, usually with an overabundance of food, right? So they are developing rapidly selected for very high rates of reproduction in the laboratory. So it’s just a fundamentally different experimental paradigm. And there’s good reason why we do that in the lab, we’re trying to control everything that we can and change only one thing in principle and see the effect of that one thing.
But of course, humans don’t live in a laboratory, and so I think companion dogs in many ways do a really good job of capturing the human environment, with the exception of diet and we can talk about diet if you’d like diet is an interesting difference, of course, between companion, dogs and people. But with the exception of diet, they really do share our environment in almost every way. And in some ways they’re exposed to aspects of the environment even more than people are like drinking water, right? Most people don’t give their dogs bottled water, they give them tap water. So it’s really powerful from that perspective. So that’s a really, I think, important and unique feature of the dog aging project.
Another one is the genetic architecture that we have already touched on. That you have genetic diversity in dogs that’s actually greater than the genetic diversity in people, but it’s also in the context of this unique architecture where you have a few hundred pure bred breeds of dogs, which are in some ways like inbred strains of mice, they’re not quite as inbred as like a C 57 black six mouse, but they’re pretty inbred. But then on top of that, you have the mixed breed population. So you really do have a heterogeneous genetic population of mixed breed dogs. So I think that’s also a really interesting and important aspect of the dog aging project that, again, is really hard to capture in laboratory animals.
Very rarely do people do studies in more than one strained background, and when they do, it’s usually only a handful, right? So this is actually a criticism that people often raise about preclinical literature from the ageing field is that it mostly comes from a relatively small number of genetic backgrounds in each of the model organisms. And it’s a valid question. If you were to take something like caloric restriction and apply it across a panel of genetic backgrounds, would it work as well? And the answer with caloric restriction is clearly no. And the studies that have been done, what we found is that about a third of genetic backgrounds in each model organism, so no response or a negative response to the same level of caloric restriction.
I think it’s an open question whether some of these interventions that we study are going to be robust across a diversity of genetic backgrounds, and we can start to address that in a diverse population. And of course, if one of the goals is to translate to humans that genetic diversity and environmental diversity is really important to understand how much of an impact it’s going to have. So I think that’s another area where the dog aging project is unique.
And of course it has the power that dogs age, about 7-10x faster than people do. So we can’t do studies in quite the same timeframe as mice, but it’s not so much longer, it only takes about two times longer, really to do studies in dogs as it does in laboratory mice. And so you can do observational, correlational, or clinical trial studies in or in a feasible timeframe in companion animals. That’s the real challenge with trying to study ageing directly, in humans age so slowly that it would be a 20 to 30 year clinical trial to try to test whether something like rapamycin slows ageing in a healthy human population if lifespan was your end point.
And I think for me, also people love dogs, like, I’m a dog person. I’ve had dogs my entire life. I’ve got a German shepherd named Dobby right now. who I love dearly, right? It’s not only about the science and what we’re going to learn about human aging. It’s about, what we can learn about aging in dogs and potentially increase the healthy longevity of companion animals.
So there is that aspect of it, which I think it just depends on your perspective, some people, and that’s partly why this project, I think, is so appealing to so many people, right? The people who want to have an impact on human ageing recognise that we can learn something about human ageing from studying it in companion dogs and the people who love animals, love their pets, also recognise that this is important and potentially valuable for them.
So I think it appeals to a pretty wide audience. I also keep coming back to the potential, how can we message the field to the general public? And I think that’s a really important aspect of the dog aging project, that not only do people understand that their pets age more rapidly than they do, but they see the value. In some ways they see it’s easier for them to see the value if we talk about increasing healthspan and lifespan in animals and their pets compared to, if we start talking about trying to do it in humans. So I think it appeals to the general public in a way that, that really not very many scientific projects do.
Chris: In science, it is well known that before you start changing something you first have to measure it. How are you measuring the biological age of the dogs in your study? What endpoints are you using?
Matt: It’s a great question, and I think, this is a bigger question for the field, right? This is something that the field as a whole, I think, is working through, struggling with, trying to figure out what is a consensus definition for biological ageing, okay. So it’s not an easy question to answer in a concise way.
I think one view, and I don’t disagree with this view, I would say, this is my preferred view: I think we have to look at lifespan. There is a component of the field that says that health span is more important, so we should look at health span and not worry about lifespan.
I think we have to look at lifespan number one, because if you’ve really impacted the biology of aging, you will by definition, impact lifespan. And number two, it’s really the most quantitative measure that we have. All of the measures of healthspan are at least overall healthspan or qualitative.
There is no single quantitative assessment of healthspan that the field agrees on. So when people, and this is a little bit of my pet peeve, and I will admit I have done this, I don’t do it anymore. When you see in the title of a paper, somebody claim that they have extended healthspan in general, they haven’t and reviewers should stop letting people put that in their titles or abstracts.
You can’t claim that you have significantly increased something you can’t measure. Because there is no quantitative way to measure healthspan, you cannot claim that you have extended healthspan. Sorry, that’s a little bit of an aside, but I think it’s an important one for people to start appreciating.
Okay. So how do we measure aging aside from lifespan? And I think there are different camps, right? I am for now, at least am in the functional camp, I like functional measures of aging. So looking at quantitative assessments of organ tissue cellular function.
So for example, by echocardiogram, looking at function of the chambers of the heart, right? Or by blood chemistry, looking at function of the kidney and the liver and things like that, or by strength tests, looking at function of muscle or activity measurement s. And look, I was trained as a molecular biologist geneticist biochemist, I understand why people gravitate towards the molecular measures, but I think if your interest is really in quality of life you really need to look at function.
And again, I see too many times the basic scientists in this field say ‘Oh, I’ve changed the epigenetic clock and reverse aging’, no you haven’t! You’ve reversed epigenetic changes that go along with aging. You really have to show that functionally you have had an impact on aging. So I like functional measures.
So in the rapamycin trial, for example, we’re looking at echocardiogram for heart function. We’re looking at neurological exams for neurological function cognitive assessments for cognitive function activity monitoring, kidney function by blood chemistry. So we are trying to, as broadly as possible, look at functional measures of aging.
Of course, we’re also looking at disease incidents. So what’s the frequency of cancer, kidney, disease, diabetes, things like that in the dogs. And then we are also collecting the molecular measures, epigenetic clocks, metabolome microbiome, but I view those as much more exploratory.
I’ll say it again, if I see in dogs that rapamycin reverses or doesn’t do anything to the epigenetic clock, let’s say there’s no change in the epigenetic clock, but the dogs are living longer and healthier. I’m going to believe the lifespan and healthspan metrics over the epigenetic clock.
So I think it’s really important to look at functional measures, if you want to look at the molecular measures too great, but I don’t view those as anywhere near, as definitive, as lifespan and functional measures of health.
So those are the kinds of things that we’re looking at in the clinical trial. In the longitudinal study, we’re collecting pretty much every kind of data that, that you could imagine on environment also genome. So we’re getting genome sequencing on 10,000 dogs. And then I mentioned epigenome, metabolome, microbiome. So we’re also doing the omics but again, the longitudinal study is much more exploratory and observational. At this point, we don’t know what the signatures are going to be that are predictive for future health outcomes. That’s part of the point of doing this.
Jared: If you had to take a side, where you you come down on? Are methylation clocks a measure of ageing itself, or a by-product of other processes?
Matt: So my view is we don’t know yet, and you’re referring specifically to the epigenetic clock. So I think, big picture, I have no doubt that we can deliver molecular clocks that are predictive for biological ageing. Specifically, are the epigenetic clocks alone going to be predictive for biological ageing?
First of all, I’ll say, I don’t know my intuition is that they will not in many situations. So I think that you can definitely find specific situations where a specific epigenetic clock is predictive. Absolutely for chronological age that’s unquestioned. And you can find individuals who fall off of that prediction for chronological age, who then are hypothesised to be biologically ageing, more rapidly or more slowly.
And you can find evidence to support that, right? Under those very specific conditions I haven’t seen anything yet that convinces me that in a general population, environmentally, genetically heterogeneous changing over time that the epigenetic clocks are actually predictive for individual future health outcomes, which is what we want.
If the clock really works you should be able to take it, you individually get an answer, change your lifestyle and see whether the clock is actually going to do a good job of predicting your future health outcomes. Again, part of the challenge with proving that in people, is that people live so long, right?
So it’s hard to do those studies, in advance, right? So what people have relied on are longitudinal datasets, there are problems with doing that as we all recognise. But you could do it in mice and nobody’s done it, and I actually think this is a real limitation to the clock field where the clock people need to actually do the right experiment here. There is absolutely no reason nobody has taken a population of old mice, measured their, whatever clock you want to measure, treat half of them with rapamycin or whatever your intervention is, and then at the individual level, show us the clock is predictive for outcomes, right? That’s a doable experiment. It shouldn’t take more than two weeks. And I feel like this is a case where people who are invested in these clocks have skipped over actually proving that they work and started selling them to other people. And I just think it’s a problem. I think it’s wrong.
Look, I get the commercial side of it, like, I don’t have any problem with people within the rules that the FDA has set up starting businesses and making money. I do have a problem with scientists doing that. I personally, I don’t think you can call yourself a scientist and then go start selling stuff that you haven’t actually tested to people. I just think you shouldn’t do that. And we see that in this field. It’s a little bit unfortunate. The other concern I have is when the same people selling the clocks are also selling the supplements that supposedly affect the clock. I worry a little bit. That sort of conflict of interest.
But I do think in general that clocks, we will be able to develop biomarkers. Again, clocks are just a sexy word for biomarkers but this is something that field’s been working on since the eighties, right? 1980s. I think we will be able to develop diagnostic predictive biomarkers for future health outcomes during ageing, probably not only involving the epigenetic clocks, but involving other parameters blood chemistry, functional measures, maybe imaging of the face, right?
There’s people working in all of those areas. My gut feeling is all of those together will give you a more precise, predictive algorithm than only the epigenetics. The other thing to say about epigenetics is, it’s a little bit of an unknown. There are some people who feel like the epigenetics are upstream of everything else in biological ageing. Again, my intuition is that’s not going to be the case and that epigenetics are only monitoring one aspect of ageing. Maybe it’s a big aspect, but I don’t think it is. I don’t think that the epigenetic changes are everything that’s happening in biological aging and, time will tell there’s a lot of enthusiasm and excitement about the reprogramming idea.
If it is the case, that the epigenetic changes with ageing are everything, then it should, in theory, be possible to, through periodic reprogramming, to make a mouse that lives I don’t want to say forever, but a long time, right? At least double the normal life span of a mouse.
And again, this is where the hype has gotten way, way ahead of the actual data. Nobody’s actually done it yet, right? Nobody’s actually showing you can increase lifespan by 30% in a mouse with reprogramming, let alone double the lifespan. I feel like people should just do the experiment instead of getting ahead of themselves and making bold claims without any actual data or much actual data, I should say.
Chris: Rapamycin is one of the most highly anticipated longevity interventions out there at the moment. Firstly what is rapamycin? For those listening who have not heard of it before.
Matt: So I’ll definitely tell you about rapamycin, but I want to comment on something you said that it’s one of the most highly anticipated, because it’s really interesting to me actually having been working on mTOR and rapamycin since, I think we first started really studying mTOR around 2003, right? This was from an unbiased screen in yeast. So having been around this pathway in the ageing field for that amount of time, it’s actually interesting the way this evolved. We found, and then a couple other labs in parallel found in yeast and worms, that if you inhibit mTOR, you can increase lifespan. Nobody really paid much attention in the field until the interventions testing program showed in 2009, that you could start treating mice with rapamycin and middle-age and extend lifespan. And then people got really excited. For about two years, and then everybody got tired of rapamycin and got interested in the newest, shiny object and nobody would pay attention.
Believe it or not, it was really hard to get any funding to study mTOR or rapamycin and ageing because the field felt like, oh, we already know about that. And it’s only been in the last, I don’t know, two years, I would say that I have really felt an uptick in interest in rapamycin again.
This happens in science sometimes there’s this pendulum that swings, and I think we still don’t know, ultimately how useful rapamycin is going to be for long lifespan and healthspan. But there is a noticeable uptick of interest in mTOR and rapamycin in the last two or three years in the field, and honestly, I’m not really sure exactly what’s driving that, except I think we’re starting to get hints that it could have some effects on people. And I think also the publicity that we’ve gotten through the dog aging project has helped because somebody is actually testing something in the real world with people appreciate.
So it’s just interesting to me how the interest level has gone up and down the fashion trends isn’t that they come round it’s happens in every scientific field. Although I think the ageing field is more prone to it. There’s definitely a shiny object syndrome in this field where people get completely fixated on, something right now it’s reprogramming. It was senolytics a few years ago. I think ultimately, some things stand the test of time, some things don’t right. And it, unfortunately, sometimes it takes a long time to figure out, what actually has an impact, and where the hype got a little bit ahead of the actual factual science.
So in any case, that was a little bit of a tangent, but so rapamycin, it’s an interesting, it’s an interesting molecule it’s produced by a bacterium that was identified on Easter island, also known as Rapanui that’s where the drug gets its name from rapa-mycin. And so it was produced by this bacteria called streptomycin hygroscopic, as it was identified in soil samples there it had a tortured history and I don’t have time and I don’t know that I could actually do a credible job of telling you the whole backstory, but it’s a really interesting backstory.
It’s still on my bucket list to make a pilgrimage to Rapanui. I feel like it’s appropriate that I do that at some point. So anyways, and eventually it was studied for a while as a anti-fungal initially, and then that is an anti-cancer drug, but it actually first got traction clinically in organ transplant patients as an immune suppressant.
So that was actually what the drug was FDA approved for. This was more than 20 years ago now for use in kidney transplant patients to prevent organ rejection. And then it got expanded as is often the case to other types of organ transplants. If you look at the clinical literature or you just do a Google search, you will definitely find, rapamycin is an immunosuppressant.
It goes by the clinical name of Sirolimus. So people get confused, but they’re exactly the same molecule, that rapamycin or sirolimus is an immune suppressant, used an organ transplant patients, but all of that’s true. In some ways it’s unfortunate that’s how the drug first was tested and approved clinically, because in that context, in sick people taking other immunosuppressants plus high doses of rapamycin, there are some side effects that go along with the drug. And so there’s some concern in the clinical community about rapamycin and other mTOR inhibitors because of the side effects that are seen in an organ transplant patients. They’re not terrible, they’re not typically life-threatening, but they’re not pleasant. And there’s some concern about them. What we’re learning is that at lower doses, most of those side effects go away, and we can dive into that a little bit later if you’re interested. But that’s the clinicals, the clinical story.
And it’s been used almost exclusively as an organ transplant patients also for some forms of cancer. Also for some diseases that are caused by mTOR hyperactivation like tuberous sclerosis but primarily organ transplant immune modulation. So it’s completely independent of that clinical youth. Again, as I was saying before, around 2002-04, about three different labs, I was involved in one and then two, and C. elegans, hit on mTOR as a regulator of lifespan. So that the development of rapamycin in the ageing field was completely independent of the clinical work, and its use in patients.
We all were doing unbiased screens where we came across mTOR as a target for lifespan manipulation in these invertebrates. And then of course, as soon as we saw mTOR, we did a Pubmed search and found that rapamycin was a drug that inhibits mTOR and thought ‘oh, maybe this drug will also affect lifespan’, and it turns out it did. And those three papers came out 2003-04, and we continued to work on mTOR and that pathway in the context of ageing. But again, it really didn’t capture the attention of the field until the interventions testing program tested rapamycin in mice, where they showed in 2009, that you could start treating mice at 20 months of age, which is about the mouse equivalent of a 60, 65 year old person and get lifespan extension.
And that’s a funny story. I don’t know if, I don’t know if you guys know the story about why they started testing it at 20 months of age. It’s a funny story.
So first of all, just a little background on the interventions testing program. So this is an NIH funded program that’s been around, since I don’t know, 2005, maybe 2004. Scientists in the field or even the general public can nominate interventions for testing on lifespan in mice. And it goes through a review process anywhere from 3-7 are selected each year to be tested, usually small molecules, but it can be dietary interventions and things like that as well.
The experiments are done at three different sites, so there’s triplicate replication built in, they’re done independently and they’re done in a genetically heterogeneous background called UMHET3, and this is because there’s a lot of concern about testing interventions and in really inbred backgrounds like C57black6.
Sometime in 2004, probably rapamycin was nominated by a professor, his last name is Sharp. And he actually, I think was inspired more by the effects of rapamycin on cancer that he was saying then by the invertebrate work that I was talking about. Anyways, he nominated rapamycin to be tested, it was selected, and then they usually start the animals at about six months of age on the intervention, six or nine months of age. It’s changed a little bit so young, but they found with rapamycin that they couldn’t get it stable in the food. So the way they deliver all the interventions is in the diet.
And they realised that the chemistry of rapamycin was such that it went bad if they just added it to the chow. But because they’re testing multiple interventions at the same time, they have a large cohort of mice, all age-matched that they have to start the interventions at a specific point in time. And so the decision was made that, well we don’t think it’ll take very long to figure out how to troubleshoot this, so we’ll start the cohort and then we’ll just give them rapamycin as soon as we get it figured out how we can stabilised in the food. It turns out it took them about a year to figure out how to stabilise it in the food.
This was work that Randy Strong at San Antonio did to figure out an encapsulation method that would stabilise the rapamycin so it could be added to the chow. So by the time they actually had that figured out the mice were, I don’t know, 17, 18 months old. And, the decision at that point had to be made, should we actually do this? Should we try it? Or should we just wait for the next cohort? And I think probably almost everybody thought there’s absolutely no way this is going to work starting at 20 months of age. Because up until that time, nobody had ever shown that any intervention that extends lifespan in mice works robustly.
If you start at 20 months of age, like it was assumed that you had to start early. And this is actually a bigger point because this is a way I think the field has fundamentally changed. Back in 2009, the dominant paradigm was that interventions slow ageing, that we are slowing the damage that accumulates with ageing.
And so the expectation was, if you start after the damage has already accumulated at best, you’re going to get incremental effects. So nobody thought this was going to work, but they made the decision to go ahead and do it anyway. And thank God they did because it worked. And so that, I think, really was a paradigm shifting moment in the field where suddenly it went from, you have to start early to get a significant benefit to ‘oh wow, we might actually be able to start in middle age and get a significant benefit for lifespan and potentially how span down the road’, and that’s really important for us. A translational perspective of really believing that you can have an impact in humans, right? Because we all recognise if we have to start treating teenagers with whatever our intervention is, that’s going to be really hard, probably not feasible, but if you can start treating people in their fifties, sixties, maybe even seventies, you really have a chance to have an impact.
So I think that was a real watershed moment in the field. The demonstration that an intervention could have a big impact starting in middle age. And now we know with mice and at least you don’t even have to do it continuously for middle age. You can treat for six weeks or three months still get pretty big effects.
So that’s that’s the backstory, it was really an accident, right? And that happens in science. Sometimes, you have these fortuitous accidents that end up having a pretty big impact because you weren’t doing what you expected to work, you found something that you didn’t expect to work.
So that’s the story with rapamycin and the ITP. And, this paradigm shift in the way we think about aging I think is really important. And we actually now have some biological understanding for how you can actually restore function. I think there’s a lot of hesitancy and deservedly.
So to talk about reversing ageing, because it really depends on how you define ageing when you talk about reversing ageing. But I think you can definitely say we can restore function and we can rejuvenate tissues and organs functionally, at least in mice. And there’s, I think pretty good evidence in people that we can, in some cases, at least rejuvenate function in tissues and organs.
And so again, that’s a really fundamentally, important change in the way people are viewing ageing biology. And I think it’s informed the way we think about ageing biology and it’s helped us understand mechanisms because the mechanisms that drive, you have to fit them to the data. And the data says that you can restore function. You have to then have biological mechanisms that allow that, and I think that’s helped us understand the ageing process better.
Chris: You recently announced on twitter your involvement with the Rapamycin study. Do you want to give us a bit more information on what this will actually be looking at?
Matt: The study itself, really its observational, so it’s not a randomised clinical trial. We’re not treating people with rapamycin, our specific study, which was funded by the Impetus Grants program. I just want to give a shout out to the Impetus program, I think that has been hugely valuable to the field. These are relatively small grants, but they’re funding a lot of projects that you would never be able to get funded through the NIH or through other governmental funding bodies. So I think it’s been really important and valuable. So this is a project that was funded by the impetus program. And the goal is really to try to collect information. From people who are currently taking rapamycin or who have taken rapamycin in the past, to try to understand what their experience has been both from: are there any perceived benefits they think they might’ve gotten from the drug and also any side effects. And we will have a control group of age and sex matched people who have never taken rapamycin to try to understand.
If you think about side effects, first of all they are a really tricky problem when you’re talking about older people, right? Just like in older dogs, right? I say this, in our trials one of the reasons why we have a placebo group is if you’ve ever had an older dog, you will recognise that in any three month period, your dog is going to have, one or more of this long list of things that include, throwing up, diarrhoea, lethargy.
The same thing’s true in old people, and independent of what they’re taking. So you really need to have an understanding of what the background frequency of some of these things that get called side effects and clinical trials is. In a clinical trial you’ve got a placebo group. In people who have been taking rapamycin off label, for potential effects on ageing, you don’t have a placebo group. And so that’s partly why we’re trying to build that in. So anyways, it’s only survey based right now. We are discussing with people who are interested in potentially trying to get samples from some of these patients, but ours is survey based and medical record and dental record review based to try to address what are the experiences of people who have been taking rapamycin off-label. Not for organ transplant, but for, in many cases, the expectation that it might impact their health and longevity.
This is actually a really interesting group of people, pretty mixed, really actually a lot of extremely successful people, in their professional lives who are also very much into, wanting to maximise their healthy longevity. So CEOs of big companies, things like that. But also then you’ve got the biohackers who are interested in living longer, who are often taking lots of other things at the same time that they’re taking rapamycin. So it’s a complicated group of people. And so I think, we’ll see what the data looks like, but the goal is really to try to at least get a feel for safety and maybe some hints about efficacy.
One of the reasons why I thought this was important to do gets back to what I talked about before, about the way rapamycin was developed as an organ transplant agent or organ transplant anti-rejection agent, the side effects that go along with that, the reputation that rapamycin and other mTOR inhibitors have in the clinical world that’s driven largely by that patient population, which is fundamentally different than people in their 50s, 60s or 70s taking, rapamycin once a week for maybe healthspan promoting benefits.
We don’t have any real data on side effects in the latter population, and so this is an effort to try to start to gather that. And hopefully, if we see that there aren’t much in the way of side effects, change clinical opinion. So the idea would be to publish this someplace where clinicians can actually see it. I’m also hopeful that we’ll identify a few interesting case reports. We’ve already got a couple of people who have had interesting experiences when they start taking rapamycin.
Again, I think clinicians, they tend to be responsive to actual patient experiences, rightly so, and so I think that, maybe these case reports can also help people to identify places where rapamycin might be particularly useful from a clinical perspective.
I just want to add as well. So that’s our study, I’m very excited about the fact that there are going to be several clinical trials, it looks like starting this year, on rapamycin for specific age-related indication. So again, two of them funded by the Impetus Program. One is a clinical trial for periodontal disease that Jonathan An at the University of Washington is setting up. This is based on work that we did in my lab, showing that we could reverse periodontal disease in old mice with rapamycin. So he’s going to do a clinical trial in people. And then Zev Williams and Yousin Suh at Colombia, are pursuing a clinical trial for early ovarian failure in women at the reproductive health centre there for rapamycin again, based on mouse data that you can actually delay or partially reverse ovarian failure in during normative ageing in mice. And then there’s another clinical trial that is being set up in New Zealand to look at muscle function and the impact of rapamycin on exercise.
So those are three that I know about that. I think, if all of those get off the ground and they’re completed, I think, might give us some pretty interesting data on specific indications where rapamycin could have beneficial effects in the context of normative agent.
Chris: For the Dog Aging trial, other than rapamycin, what other interventions are the dog aging project investigating?
Matt: We’re not currently, and it’s funny because I get, I must get an email once a month from somebody who wants me to test their particular intervention in my inbox. And sometimes, sometimes it’s crazy, but sometimes they’re really good ideas, right? Like these things really should be tested.
The fact is that is, it’s a lot of work, and that’s the understated way of saying what it takes to actually design a clinical trial like this and execute it. So just to give you a feel for the rapamycin study, to have a statistical power, to detect a 9% change in lifespan in dogs it’s a three year study with 580 dogs, right?
So that’s a big for veterinary clinical trials. That’s a big clinical trial. And so just figuring out the logistics of how you do that, where your clinical sites are identifying the veterinarians, who want to participate.
And I’ll say veterinary medicine, it’s not like human medicine in the sense that there are a lot of clinical trialists right. Most veterinary clinical trials have been relatively small, usually one centre trials, and there’s a lot of logistics that have gone into building this. I think it will be easier now. And one of the reasons, again, I recognise this early on, you don’t know when you do a clinical trial, whether it’s going to work, right. And sometimes clinical trials can fail. Even if the intervention itself works for a variety of reasons. So recognising that, I knew going in that one important thing we could do with triad is build a template for how you do longevity clinical trials in dogs. And I think we’ve done that.
I think we’ve created a model that other people can follow. I just don’t have the bandwidth to do it right now. So the answer to your question is – no, we’re not testing other interventions, but I think there are a handful, that it makes sense to test in dogs right now, again, because these are people’s pets you really have to think hard about safety and you have to be sure, and you have to do the safety trials to make sure that it’s very unlikely you’re going to hurt anybody’s pet badly. I think of it almost like a pediatric clinical trial in that sense. People feel very similarly about their pets as they do about their children. So safety has to be paramount so some of the things you might think about testing, because we can test them in mice, aren’t going to be suitable for testing in dogs because of concerns about safety.
But I still think there are probably, at least right now, we could come up with a set of 5 to 10 interventions where there’s enough data that it probably makes sense to test them in dogs, maybe not for lifespan, but maybe for specific age related indications.
Antonia: What are, in your opinion, the major drivers and factors that increase/decrease canine lifespan?
Matt: It’s interesting because in some ways it’s very similar to human longevity, in a general sense, right? So we know that obesity is an increasing problem in pets and that obesity in pets leads to a variety of higher risk for diseases and negative outcomes during ageing.
We know that lack of exercise is a problem that can impact later health in life in pets. So I think, much like in people, those are probably two of the most important factors that are also the most easily fixed at least easily from a conceptual perspective. Maybe not easy from a pragmatic or in practice perspective, but, in many ways it’s very much like humans. It is the case that older dogs do show a somewhat different disease spectrum than people do. Just like in people, cancers increase exponentially with age in dogs, so by, but even more so cancer is probably the single most important lifespan limiting disease in dogs.
So obviously, if you had a way to cure all cancers, you would expect that to have a significant impact on dog life expectancy. I would suggest that a cure for cancer is going to be just as difficult in dogs as it is in people, and by that, pretty much impossible at the population level. I think this idea that we are going to completely eradicate all forms of cancer is just not based on what we know about biological reality right now, but I think you would expect it to have an impact on life expectancy in dogs.
Dogs don’t get a lot of vascular disease. Things that impact vascular disease in humans probably are going to have a lower impact than in dogs. They do get a lot of kidney disease, so interventions that would impact kidney disease. So again, I think it’s very similar to people in a lot of ways.
In terms of what can owners do, right now to have a positive impact on the health of their dogs? Again, I think it comes back to what we already more or less know, right? Make sure your dog is not obese, exercise your dog regularly, get it vaccinated – I’m sorry to all the vaccine deniers out there, but it is a fact that vaccines help, at least for some things – take your dog to the vet regularly, get a regular checkup. Oh, the one that almost everybody does not pay enough attention to is oral health.
And this is true in dogs, it’s also true in people, brush your dog’s teeth. I get why people are hesitant to take your dog in for a dental exam. If it requires anesthesia, I admit I’m also hesitant to do that with my dog, unless he needs to be under anesthesia for a different reason, but it’s easy to brush your dog’s teeth. It’s really easy do it! It’s surprising how few people recognise how much periodontal disease and poor oral health increases. In both people and dogs, the risk for a variety of other age related diseases.
So there’s a fundamental connection there that I believe is related to the biology of ageing. That if you have poor oral health, you have higher systemic inflammation, which leads to dysfunction throughout the rest of the body, or contributes to dysfunction throughout the rest of the body. So that’s something that everybody can do. That’s pretty easy in dogs and you shouldn’t do it, and it’s under-appreciated.
I have no idea if I actually answered the question you were asking, but hopefully it was good content regardless.
Antonia: Are there any other products or treatments that you can think of that might be very promising for the future?
Matt: I don’t want to recommend any specific product. First of all, I’m not a veterinarian, so I’m careful not to recommend, specific commercial products. I feel okay saying brush your dog’s teeth. I don’t think I have to be a veterinarian to say that, but I don’t want to recommend any products.
I am encouraged that there is a growing interest among companies and academics in this area of, veterinary geroscience, I just made that up, but I think it’s going to be a growing area of interest and importance going forward. This recognition that we have an opportunity to significantly impact healthy longevity in pets by targeting the biology of ageing. And I’ve been very encouraged to see, a dramatic growth in people thinking about that.
Now I should say it’s been a dramatic growth because for a long time, we were really the only ones with the dog aging project thinking about it. So when you go from 1-10, that’s a big growth but I think it’s exciting to see that there are people, including companies now, which is really great, right? There are some biotech companies and even some big companies that I’ve been contacted by who are looking at the biology of ageing as a target for for healthy longevity in pets, including, big multinational corporations that are the giant in anything to do with veterinary medicine, and I’m not going to name them, but anybody who knows anything about veterinary medicine knows who I’m talking about. They have a specific interest in ageing as a target for health in veterinary medicine. So I think that’s really great, and I think that that will only accelerate the understanding of aging and companion animals and our ability to have an impact on health and longevity and companion animals by through that understanding.
That may end up being drugs like rapamycin, it may end up being nutritional strategies, it may end up being other sorts of environmental changes that can be made. I think it will probably actually end up being a combination of all of those things, as well as preventative measures, or diagnostics. I think there’s a place for all of those things to have an impact.
Antonia: What are some of the biggest challenges with working with dogs as an animal model?
Matt: So there are a few, I would say, one that I appreciated and I already alluded to this going in, especially for a clinical trial, is the safety, right? Because these are very much like people’s children. In fact, more than half of pet owners consider their pet to be part of their family, and they view them very much like a child. You really want to make sure you’re not going to hurt anybody’s dog. So that limits the kind of interventions that you would ethically want to consider testing and companion animals. I’m not saying that’s a bad thing. I actually think it’s a good thing, but it does it has been a little bit of a challenge because you really have to make sure before you start a large clinical trial that you can do this safely. So that’s one.
I think, I also alluded to the fact that veterinary medicine is pretty small compared to human medicine. There are not that many veterinarians at veterinary teaching hospitals with clinical trials experience who do that as a big part of their career or their day to day experience.
So you really have a small number of people that you can collaborate with to carry off these large clinical trials which makes it a little more challenging. It’s also hard because most veterinary clinics, private practice clinics they don’t have the same capabilities that a human medical clinic would have in a lot of ways, and they’re really busy, right? These veterinarians are going from patient to patient. They don’t have time really to participate in a scientific study. You have to figure out ways to, first of all, identify those veterinarians who really want to participate, but also continue to engage them in the process.Again it’s easier to do that in human medicine because you have physicians who specialise in participating in scientific studies or in clinical trials. So that’s been a little bit of a challenge.
We’ve been very fortunate that it hasn’t been so hard to recruit dogs into the overall dog ageing project. We’d obviously love to have more, but we’ve got about 37,000 dogs in the longitudinal study right now. And I think that, again, just reflects the fact that people love their dogs and they like to talk about their dogs, and they’re excited about participating in a scientific project that’s about their dogs and might have an impact on their dog. So that part hasn’t been hard.
We will see as we go forward, how challenging it is to retain participation. Recruiting hasn’t been a huge challenge, retention is a little bit of an unknown, so we’ll see. The other thing I should say is I think, our unique experience with the dog aging project has of course happened during a global pandemic, right? Some of the challenges around actually building the clinical trial and, getting the veterinarians on board and getting the clinic set up to do the study, obviously that has been impacted by lockdowns and emergency procedures only, and things like that. So I’m hopeful that as the world comes out of this level pandemic things will get easier in that sense. And people won’t be so overwhelmed with just trying to get through the day. So I think our experience may not be completely normal in that sense going forward.
Antonia: What makes dogs a better and more unique model in which to study ageing, when compared to classic models?
Matt: First of all, let me take a step back because I think this is, in some ways, is a little bit of a myth. The idea that animal models have a terrible record of translating through to humans. First of all, the context of ageing, we have no data, right, there is no data on an intervention that worked in an animal model and failed in humans. That doesn’t mean that when we actually do the trials, that won’t happen, but we don’t have any data. So it’s an N=0 there. So we can’t say anything about that. People often point to cancer as an example ‘We’ve cured cancer a million times in mice and it didn’t work in people’, and that’s true. But I actually would suggest that maybe the major reason why the animal models have failed to be as good a translation as we would hope is not because of the animals, the mice themselves. It is because of the flawed way that the biomedical community has used them. In particular, I’m referring to the fact that most of the diseases where the animal models have failed miserably are cases where it’s an age-associated disease and people have tried to artificially create the disease in a young animal. This is a frustration point for me and that I’m trying to communicate to the non-gero scientists in the world. It seems like it should be obvious, the physiology of a young mouse or a young person is fundamentally different than the physiology of an old mouse or an old person. And so when you take a disease that in the real world happens in the physiology of an old person and you try to model it in a young mouse, it’s not shocking that is not a very good model.
So all of that is to say, I’m not sure it’s only, or even primarily, the mouse to human problem here. I think it’s the fact that most of these people have been studying diseases of ageing in a young physiology, and it’s just completely different. So I don’t accept yet, that the premise that mice are not a good model for X (disease) , when you have used the mice improperly, from an experimental perspective.
Okay, so that’s my tirade on that. So, why are dogs better? So again, I don’t know if they’re better, but I think they should reflect the human situation more than a laboratory mouse. So one is, they share our environment, we’ve already talked about that, they’re genetically diverse, we’ve already talked about that, and you can in fact study these diseases or functional declines in the real world, in an old animal, that’s experiencing the real world, and you can do it in a reasonable timeframe. So I think that’s the real power from a biological perspective of dogs as potentially a better model for diseases of human aging or functional declines of human ageing.
But, I think again, we do have to admit that’s all intuitive and it makes sense. We don’t actually know that dogs are going to be a better model for human ageing. I believe they probably will for those reasons, but time will tell, we have to get the data and we have to actually find out everything that I know, and this comes in part from having old dogs. I’ve had several of the old dogs in my life. They get old very much like we do. And I’ve known several old people in my life because I’m sure you all have right. All dogs show a lot of the same functional changes, behavioural changes that old humans do, and so they look like, just from the phenotypic output, it looks a lot like human ageing. And again, I think we can see that more in dogs obviously than we can in laboratory mice. We can see a greater diversity of phenotypes of ageing in dogs than we can in laboratory mice. So I feel pretty good about the idea that at a cellular, molecular, functional, phenotypic, and all of those levels, there are aspects of ageing that are very highly shared between dogs and people.
Antonia: Have there been any specific implications at this stage that we can already draw from the findings that you have gathered from research with dogs as an animal model to human longevity?
Matt: I don’t know that there’s anything I feel a hundred percent confident about. First of all, I would say there’s not a lot about human longevity that we should feel a hundred percent confident about. I think it’s a matter of growing information and data availability, and then making the best guests you can at that point. So what I would say is, I think we can be pretty sure that just like in peoples relationship between obesity and health, outcomes and lifespan is pretty similar relationship between exercise and those things is pretty similar.
In terms of specifically what we’ve learned from the dog aging project, I don’t know that there’s anything I feel a hundred percent confident about. It seems like with rapamycin, just from our two safety trials, it does seem to be the case, in both of those trials, only one of which has been published, the owner’s self reported that the dogs getting rapamycin were more active and the owners didn’t know if their dogs were getting placebo or rapamycin. That suggests to me one possibility, and this is anecdotally what people have reported in older people taking rapamycin.
One possibility is that the effects of rapamycin on systemic inflammation are reducing chronic pain in old dogs and that’s observed as increased activity. Again, that’s very speculative and it’s not quantitative, but the fact that it came out of both studies, owner reported without us even specifically asking about activity makes me think it’s probably real. I’m being careful to say, that’s what I think. I don’t know, but I think that it gives me a fair amount of confidence.
If you asked me what my prediction is for rapamycin in humans, I would say I’m pretty confident that rapamycin has benefits in healthy, older people for at least some aspects of biological ageing and in particular, from my own personal experience, and from people I know it seems to be really pretty effective at age related inflammatory conditions in joints and capsules. And so it would not shock me if there are benefits for things like arthritis or inflammation of shoulder capsule, which was my experience and the pain that goes along with it. Again, I can’t prove it. I haven’t done a clinical trial, but I feel pretty personally confident that’s probably the case.
Antonia: Dogs are often called ‘Mans best friend’. What impact do you think it will have on the general population if the dog ageing project is successful and we are able to significantly increase the lifespan of humanity’s greatest companion?
Matt: I think that’s certainly something that I thought a lot about when first embarking on the dog aging project, the potential for this project to change the way that a lot of people think about ageing. So I already alluded to the idea that I think dogs are actually, really valuable examples for just the fact that the ageing rate is different between different animals, right? Seven dog years, one human year. So I think that’s powerful.
But of course if we get to the point, let’s say four years from now, when we unblind Triad and we look at the data where we can say that in a large clinical trial, rapamycin slows ageing in dogs. And by that, significantly increases lifespan and significantly reduces functional declines or diseases of ageing, if that’s the outcome of that trial; yes, I think that could have a big impact on public perception of the field of geroscience and also clinical practice.
Again, obviously people aren’t going to immediately assume that because it works in dogs, it works in humans, but some will. And certainly I could see many veterinarians becoming comfortable with prescribing rapamycin at that point, especially if the safety data looked, the way we expect, they’re really going to be very little in the way of side effects.
So yeah, I think it could have a big impact from a clinical perspective. And then of course, for those people who consider their pet their companion animal to be part of their family, if you can say, we have a way to give a family member extra healthy years, that’s a big deal that will resonate, I think with a lot of the general public.
Again, I try not to get too far ahead of myself because as I said, we don’t know the clinical trial is going to work. It’s quite possible that we’ll get to the end of the trial and have, it’ll be suggestive, but maybe not definitive and so I don’t wanna, I don’t want to count on that happening. But if it is definitive, then it will have a big impact.
I’m hopeful that independent of the clinical trial though, that the dog aging project itself can help expand the recognition and understanding among the general public of ageing as a biological process of the geroscience paradigm, and that there’s actually progress being made in this field. I think we all recognise that there’s a constant battle and push and pull with the snake oil, and the hype ,and the science fiction side of the equation where it sometimes seems very challenging for the rigorous legitimate scientists to have a chance against that stuff. But I think this is a case where we might be able to have an impact on public perception and help people to understand that. Yeah, sure. There’s a lot of noise out there and there’s a lot of nonsense. But there’s also real science and real progress being made here. And that we’ve actually have the potential to have an impact on ageing biology.
And it’s not a huge leap, once they accept that’s possible in their pets, it’s not a huge conceptually leap for them to accept that it’s possible in their friends and family members and in themselves. So I think it can have an impact there as well.
Jared: The mouse fasting protocol of a single day, is equivalent to around 15-20 days of fasting in humans. Do you think that, qualitatively, rapamycin acts in a different way?
Matt: I think that’s a really important question. I think it’s important to also recognise even in dogs the relationship between metabolism and caloric restriction or fasting, particularly fasting the length of the fast and its effect on metabolism is fundamentally different in mice and dogs and people.
So dogs, at least this is my understanding. They don’t go into ketogenesis for several days when they’re fasting. Whereas people, often will go into ketogenesis within 24 to 36 hours. So it’s different there too. There’s different than mice and is different than people.
So this question of rapamycin is somehow, you might be, this might be a similar sort of paradigm where, same dosing or same duration of rapamycin in a mouse is different than a dog is different than a person. Again, we have to be honest, we don’t know the answer to that.
I’m encouraged by both our 10-week study in dogs and the six month study where we saw the activity of reported activity effects. And then in 10 weeks we saw effects on cardiac function. That gives me some encouragement that shorter time periods in dogs with rapamycin comparable to what we do in mice, which, the transient treatments with rapamycin in mice are usually eight weeks to three month and big effects on, periodontal disease, reversal of periodontal disease, reversal apart function, restoration of immune function improvement in cognitive function, all in that sort of eight week, 8-12 week period. So that gives me some reason to think that it might work the same way in dogs in that timeframe.
And then similarly, the two clinical trials from June, group with ever alignments, the rapamycin derivative where they treated for six weeks and they found some evidence for it, for improvement in response to a flu vaccine. This isn’t healthy, older people. Also, suggestive that similar timeframes in people might be responsive to rapamycin.
And again, I alluded to this, I’ve talked about it on Peter Thiel’s podcast. My personal experience with frozen shoulder was that in 10 weeks, I had basically a complete reversal, complete cure of frozen shoulder, 10 weeks of rapamycin. I feel relatively confident that we can get some of the effects on inflammation, at least in that 10 week period.
I don’t know whether or not the other sorts of age-related outcomes will require a fundamentally different time period. This is really one of the challenges, right? With any intervention you want to think about testing in a clinical trial in dogs or in people, there are so many variations on dose and duration and patient population and all that you have.
Take your best guess at where you’re going to see a positive signal and then go for it because you could, you can spend your entire life trying to game the system and come up with a completely optimal strategy and you can’t test everything. So that’s what gives me hope that’s the case.
I also want to make a comment though, cause there’s a lot of confusion in the field about fasting. If you actually look at the mouse data, the evidence in mice that fasting increases lifespan is really poor. There’s very little, there’s one study that I’m aware of from Rafael de Cabo’s lab, where they mostly controlled for caloric consumption and they get about about a 9% increase in lifespan in that study, almost all the other studies on fasting, mimicking diet or intermittent fasting, the mice are calorically restricted. So it’s not a true study of the effects of fasting. It’s a study of caloric restriction.
The other thing I’ll say about that one study, I just mentioned where they got a small increase in lifespan. The controls were pretty short-lived in that study. And it’s a question whether if you did that same study and you really carefully controlled for caloric consumption in a longer lived population where the controls, were as long lived as they normally are, would you even get a nine or 10% increase in lifespan?
So there’s this perception ‘Oh yeah, fasting slows ageing and increases lifespan in mice’, and a lot of people share that. But if you actually look at the data, it’s not so convincing that fasting is a a robust way to increase lifespan in mice. I think you can get some small effects, but it’s nowhere near as effective, at least so far as rapamycin or true caloric restriction.
Chris: Where can people keep up with your work with the Dog Aging Project and also the other rapamycin studies?
Matt: The Dog Aging Project website is dogagingproject.org, and we are absolutely still recruiting dogs into both the longitudinal study and the rapamycin clinical trial, particularly.
For the longitudinal study, we would like to have more young dogs and puppies. So if anybody has a dog that, that you’re interested in participating in the study, please go to the website. It’s a really easy nomination process. And and join the dog aging project pack for now it’s restricted to the United States, but I’m hopeful that at some point in the relatively near future, we’ll be able to open it up to two dogs internationally.
And then for our human study the website is rapamycinstudy.org. And we are absolutely interested in obtaining data from anybody who has ever used rapamycin. And as I mentioned we are also going to have a sex and age matched control group of people who’ve never used rapamycin. So certainly if people are interested in participating in that study I would encourage you to go to the website.
It’s pretty easy. It’s a series of about eight survey modules. They each only take three or four minutes, so it’s a it’s pretty quick. And definitely we would love have people participate.
We really appreciate Matt for taking the time out of their day to come and talk to us. A massive thank you from Chris, Antonia, Jared and everyone on the Gowing life team.
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