155: Can Psilocybin Extend Cellular Lifespan?

In this episode, Dr. Louise Hecker joins us to discuss her groundbreaking research on psilocybin, exploring its potential to extend cellular lifespan and improve health outcomes in aging.

We delve into the mechanisms behind psilocybin's effects, findings from animal studies, and the challenges faced in conducting research on this Schedule I substance.

Dr. Hecker emphasizes the importance of understanding optimal dosing protocols and safety considerations for future applications of psilocybin in geroprotection.

Learn more about Dr. Louise Hecker:

https://med.emory.edu/directory/profile/?u=LHECKER

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Transcript

Disclaimer: This transcript was generated by AI and may not be 100% accurate. If you notice any errors or corrections, please email us at phil@longevityroadmap.com.

    What was interesting was that, uh, not only did the mice look better with treatment, but the mice at the end of the psilocybin treatment looked better than they did at the start of the experiment.

Welcome back to Longevity Roadmap. This is Buck Joffrey. And, uh, today a very, very interesting, uh, topic. I kind of ran into this article. While I was perusing, uh, through some longevity stuff, but it was an article, um, by, uh, Dr. Louise Hecker and her colleagues over at Baylor. And effectively the idea is that psilocybin, you may recall from magic mushrooms, for example.

Um, may have a role in longevity and actually, um, the data they presented in that paper was pretty strong. Uh, it's pretty, pretty potent in terms of longevity benefits, uh, for human cells as well as in mice. Um, it's an interesting idea. Uh. If you've listened to this show for, you know, a while, you know, we've had, uh, people talk about psilocybin in the context of PTSD in the context of, you know, uh, depression, that kind of thing.

Uh, usually these types of things, uh, that are, you know, psychiatric. But this is a completely different angle. This is suggesting that there might be something in the active compound, uh, the active, uh, metabolite, uh, which is, uh, Sila Orin. However you wanna say that, that may actually be jro protective. Um, not really sure how, uh, there's been some suggestion as you'll hear from this, um, discussion about potentially the role of, uh, omere lengthening, which by the way, um, I believe you should already have a show on.

I just recently interviewed. The guy who discovered the telomerase gene. So, uh, interesting reference point there. Anyway, fascinating conversation for those of you who particularly have an interest in. Psilocybin and, uh, mushrooms and microdosing and all that kind of stuff, and we will have that conversation for you right after these messages.

Hey, longevity enthusiast. It's time to take you to the next level. I've been fine tuning my longevity regimen for years, and I look better and feel better than I did a decade ago. In fact, my blood work is even better than it was back then, and it's all because of my data-driven regimen. And it's inspired me to create a course and community just for you.

It's called the Longevity Roadmap, and I urge you to check it out. If you're tired of your belly fat, tired of being tired, or just wanna optimize yourself for the next 50 years, visit longevity roadmap.com. That's longevity roadmap.com. Welcome back to the program. Today, my guest on Longevity Roadmap is Dr.

Louise Hecker. Uh, Dr. Hecker is an associate professor. Of medicine at Baylor College of Medicine, um, a Georgia Alliance distinguished investigator and a research scientist at Atlanta VA Healthcare System. She holds a BA in biology, MS in cell and developmental Biology and PhD in applied Physics, all from the University of Michigan.

And her lab made, uh, international headlines fairly recently here with a groundbreaking study showing that psilocybin has, uh, active meta, the active metabolite of psilocybin rather. Silas, uh, can extend the lifespan of human fibroblasts and improve survival in age mice. So I definitely wanted to speak with her.

Welcome, Dr. Hecker. How are you? Great. Thanks for having me on the show. You bet. And, uh, so this is, this is kind of a, um, intriguing thing. I just, you know, it kind of popped up in my feed and I was like, wow. I was, you know, we've, we've talked about psilocybin for a number of things. Um. You know that, that, that's been in the news.

But let's start with this. I mean, obviously best known as a psychedelic. Uh, what made you suspect that it might have some relevance, uh, for aging biology? Yeah, I mean, it all really just started with a friend asking me questions about psilocybin, uh, that I didn't know how to answer. And I just decided to do some reading on PubMed and learn about psilocybin.

And I was kind of instantly intrigued, um, by, you know, what we know about this drug, uh, that had been in so many different clinical trials. It's been showing efficacy for so many different disease indications. And so, um, you know, how is it doing that? How is it working for so many different diseases? And so that was kind of my first point that I found very, I mean, there's very few drugs that work for so many different disease indications.

What, what were some of those, you know, either anecdotal or preclinical things that kind of piqued your in? I mean, so it's interesting 'cause as a controlled substance, uh, one of the, one of the criteria to be a controlled substance is this potential for addiction, but yet it's being used to treat addiction.

Um, so I thought that was interesting. It's being used for all types of like, you know, anxiety, PTSD, depression, um, even chronic pain, um, demoralization. So a, a lot of different disease indications. And then I found this one hypothesis that somebody, this medical hypothesis, this one had put out there saying, um, maybe, you know, because there's this body of evidence that supports that shorter telomeres are associated with negative psychological states like anxiety and depression, and longer telomeres are associated with positive psychological states.

And we know from clinical evidence that. Psilocybin is doing something to these psychological states that maybe it's acting, uh, it's having some kind of quantifiable impact on telomere length. And so as someone who studies aging and injury repair, I thought that I could actually test that. And that's kind of where it started.

Um, interesting. So, um, so you showed psilocybin extended the lifespan of human fibroblasts. Right? So basically a type of human cell, um. So tell us about those findings. Like what, what specifically did you, uh, do and what did you find? Yeah, so we started with, um, you know, cells have a natural lifespan, uh, just like people and they can only divide so many times.

So there are these, so you can essentially watch the cellular lifespan over time and you can. Use an intervention like psilocybin and just see how that impacts cell lifespan. So, and actually we use psilocin, which is the active, as you said, the active metabolite of psilocybin. Um, that's what the cells see in the body.

And yeah, I was actually surprised to find that, uh, 'cause when you think of serotonin targeting. Um, drugs, you think, you think of the brain, but actually most cells in the body express those receptors. And so we thought, well, you know, since we already know a lot about what's happening in the brain and we, we know a lot about clinical, you know, outcomes, let's look at other cell types that haven't been tested.

So I happened to be a fibroblast person, so we had fibroblasts handy in the lab and so we used fibroblasts. And fibroblasts are also. Um, a well validated model of, of replicated senescence. So we know we have kind of this, uh, you know, we, we already have a pretty good understanding of what that normal cellular lifespan looks like in fiberglass and when they, and so that the first experiment was, was simple just treating cells with cy or vehicle and watching their cellular lifespan or quantifying their cellular lifespan.

And what we found is that in a dose dependent way. Uh, so you get more cy you have even higher extension of cellular lifespan. Interesting. Um, curious if you measured other markers with that? You know, it's funny that we were talking a little bit about omere lengthening because my, my last, literally like I do, yes.

Yesterday I spoke to the guy who discovered, uh, telomerase and uh, and one of the things he was pointing out is that from. Birth onward. We, we know we don't make telomerase anymore. Oh, wow. And that, that actually, the lengthening, uh, the lengthening of telomeres is sort of a, a, a separate phenomena just based on cell cycles and, you know, people who are finding that, uh, activities such as, you know, uh, hyperbaric oxygen or whatever, that's, that's lengthening telomeres.

It's actually because of. The elimination of short telomere cells and sort of creating an average. So the point I'm trying to make is his research and what he's trying to do now is figuring out novel ways to actually trigger telomerase because, um, you know, we are one of the species that actually telomerase is not active in repairing these, you know, telomere lengths.

Uh. Whereas, you know, in a number of other species, telomerase is there throughout life and, uh, those species don't get cancer, for example. So, so I, I was just curious, I mean, I'm, I'm sure you didn't necessarily look at telomerase, but if you looked at any other, um, any type of other, uh, markers in these cells that might have indicated what, what was going on?

As far as telium length goes, we, we measured average telomere length in these cells. Um, and so that's just kind of a standard way that we can, we can look to see how this is impacting telomere length. Uh, but we look at so many other different markers. Um, like for example, P 16, which is cell cycle arrest marker.

We see. Um, that's typically increased with age as cells, you know, tend to stop dividing. You see more cell increase in cell cycle arrest marker, like P 16. So that was decreased. We saw evidence of kind of markers suggesting that they have, um, better DNA repair mechanism in place. Uh, we saw increase, uh, SIR, two in one expression, which is kind of known.

To be kind of this master, you know, antiaging, uh, marker. Uh, we saw that there were decreased markers of NOx four, which is a master regulator of oxidant production. So the cells had less oxidant production, and at the same time they had higher NRF two levels, which is a master regular antioxidant responses.

So you have less oxidants being produced, more antioxidant responses, and then the net effect of that is decreased oxidative stress. How much, how much longer did those, uh, cells live? Yeah, so I think with like 10 micromolar, and we repeated this in two different cell types. We repeated this in lung fibroblasts and then also in adult, uh, dermal fibroblasts and results were really similar in both cell types.

Uh, so I think 10 micromolar. Was somewhere around 30% life extension. And when you go up to a hundred micromolar, you get, uh, up to like 50 something percent life, cellular life extension. Wow, that's incredible. Um, so how about the mice? 'cause you, you also looked at age mice. Um, by the way, the mice apparently do create telomerase, so yeah, I stayed away because mice and telomeres and, and you know, humans and it's very different.

So I didn't want to, I didn't wanna get into that with the mice. Mice had, uh, long, much, much longer telomeres than humans do. Uh, so it's a more challenging. Task to really, to use mice as a, you know, to, to make that comparison. In mice, what we really wanted to do is to look at longevity, but we weren't able to do that study.

Um, because at the time, you know, there were just wasn't any evidence that this was going to work. It was just based on our unpublished cellular data. Um, so we had a really difficult time getting that type of study approved, but what the, the, um, animal care would approve was a study. To look at how it impacts, um, median survival.

And so, so basically we were, our endpoint was survival. Does this improve survival? And so we gave a high dose once a month to the mice. We started out with mice that were, uh, 19 months old, which is equivalent of about 60 to 65 human years. And, uh, because we wanted this to be a realistic kind of intervention type of experiment.

Um, and uh, what we found is that median survival for the control group was about. 29 months of age. So when 50% of those mice had died, we still had 80% survival in the psilocybin treated group. Wow. Um, other, other health span measures, mobility, cognition, resilience, distress, things like that. Yeah. So, uh, some of the things that we could visually see and, um, and at the time I didn't really know how to quantify, but, uh, the mice visually just looked better.

They had, you know, mice, you know, you can see in the control group when they start, I mean, the aged mice kind of just like aged people. They have, you know, patch, you know, they're kind of, their hair is starting to get bald spots. They having some, some graying whitening of the hair. So they had some of that to start as we started the experiment.

And what, what was interesting was that, uh, not only did the mice look better with treatment. The mice at the end of the psilocybin treatment looked better than they did at the start of the experiment. So, you know, the bald spot they had grew back hair and the white hair, they had grew back in black. So they had these kind of really dramatic phenotypic, um, changes that, again, I didn't, the only way I knew how to document was just photographic evidence.

Yeah, yeah. So there's no like biological clock epigenetic data, that kind of thing. We actually, okay, so you're getting into good, good questions here. Um, I wanna point out too is I, I know like in, if you're thinking about this from like, what would I test? You know, every, there's so many things that we wanted to test, but the reality is that.

We are restricted by funding, by, you know, things that we have to do this research. And at the time I had a really tough time getting funding for this project. So I had submitted many federal grants and they just got blown out of the water because there was no evidence out there at the time. Um, things that were, that were getting, uh, you know, I was getting ripped on for, were like, well, it's a Schedule one drug.

Well, I know it's a schedule one drug, so I mean. Things I can't, I have no control over. So it was, this was a, this was not, uh, I wasn't able to get a, a large amount of funding. What I was able to get was pilot funding from, from Emory, uh, to, to do this kind of high risk study. And so, so keeping that in mind, uh, I did what I could with the, with the pilot funding that I had.

And, uh, so the end goal was, let's look at survival, right? Which is what we did. Now that said, with the remaining pilot funding that we had left, we collected as much data as we could and that, so we collected, you know, um, bulk RN Aeq from every organ we did proteomic profiling on in the blood. So we haven't published all of this yet.

Uh, we did epigenetic profiling. We have a ton more data that we're still sifting through, uh, that. We'll, we'll put out at some point, but we do have some answers. I can't, I can't give you all the, the, yeah, we'll we have to wait, we have to wait for the publishing a little longer. We have to wait. We're still, you know, again, trying to get, now that we have the paper out, trying to get some additional funding.

'cause it takes teams of people to, to do the, I don't, I'm not a bioinformatics person, so I have to hire a whole team of people to, um, to take the data that I collected and help me to, um, sort through that. Yeah. Which, you know, it's interesting. So what, what do you think your next step would be? I mean, you know, the thing that comes to mind to me is, gosh, there should be something that, uh, you know, in interventions, uh, testing programs should be looking at.

I mean, they're right. I think that we know that, that the elderly have worse outcomes when it comes to so many different diseases. COVID is one good example that I, I think everyone can relate to. We are all sort of exposed to COVID. Similarly, but we know from epidemiology data that it, the older age that you are the worst outcomes you have from COVID.

And so, you know, as a scientist, what I've tried to do my whole life is try to understand what specifically. Is different about that age individual and try to target that one thing. But maybe we should take a step back from that and think about, you know, because the fact of the matter is, it's not just COVID.

There's so many disease indications where you have worse outcomes with aging. And so one idea. Kind of the big picture idea from all this work for me and the holy grail is what if you can slow the aging process in general? What if you just forget about individual diseases and you focus more on slowing that aging process that may help a host of all different disease outcomes, you know, to be better, to have better outcomes.

So, so that, that to me is like the. Again, the holy grail of this research is can we use this as an intervention to improve age associated disease outcomes? Did you guys look at any inflammatory markers? Because one, one of the things, and I think about like sort of this, you know, this very broad decrease in morbidity and this increase in lifespan and decrease in various health problems, it makes me think of inflammation.

And as you know, a number of the, uh, the drugs that are out there, including rapamycin, which has, you know, been very, uh, celebrated as, as potentially as a, a longevity, a zero protective drug. Um, you know, a lot of the major effects are around. Yeah. Inflammation. Yeah, we, uh, well I, again, I can tell you that, um, 'cause it's unpublished data that we are looking at that and there are some really interesting impacts on, on inflammation and so hopefully, we'll, we'll have that out in the general public very soon.

Yeah. Yeah. Got it. Anything unusual in terms of the findings of the types of, you know, the, the types of mice that were, were. Getting better responses. For example, you see again in some of the intervention testing program drugs, that they're often tech specific responses, for example, anything like that.

Yeah. So that's one thing we didn't get to test. Uh, again, this is like part of the kind of limitations that you have when you're dealing with, with small amount of pilot funding, is you have to kind of like pick and choose. Battles and the things that you really wanna test. And so, um, for that reason, uh, because again, we had limited funding, we didn't have the money to test both sexes.

We, we didn't wanna add that as a confounding variable with this. So typically when you see an aging study, you know, it's like starting out with like a hundred mice and mice are aged, mice are very, very expensive. So, um. Without that type of funding available to us, we had to start out with 30 mice per group.

Uh, so we didn't wanna add another confounding variable being sex specific differences that could exist. So we, we don't know the answer to that question. Something that we do need to test for sure, we use female mice in this study, but we certainly need to, um, validate these findings using male mice. Yeah.

Uh, have you, have you found anything, uh, I guess small. Pile of studies. Is anything sort of correlative, uh, in humans, in, in the literature right now? I mean, I know you mentioned sort of some specific things like PTSD and all that, but as it relates specifically to any of the, you know, longevity related, uh, issues, psilocybin, psilocybins been around for so long.

And, um, and actually one of the things that we've recently done, we're also about to publish this, is, is take a look at the, the funding and publishing map of psilocybin. Like what has ever been published in the US on psilocybin studies and who's funded it. And what I've, we found is pretty surprising, which is that there haven't really been that many, uh, psilocybin.

Published studies in the us. I mean like if you think about it relative to something else, like resveratrol for example, 20,000 studies, there are only about 300 plus studies ever in the US on psilocybin, and that's kind of surprising if you think about how many clinical trials it's been in and, and how long we've known about psilocybin.

And part of that, a reason for that is because of the regulatory. Challenges associated with working with a Schedule one drug. So it's not easy to work with Schedule one drug. Um, it was, uh, you know, it was something that was, I didn't know anything about when I started doing this work was I just thought I would just walk into the lab the next day and order some psilocybin.

I didn't realize, you know, there is like a long process before you can even have it in your lab. I mean, I'm talking like maybe even a year. You have to obtain a DEA license. You have to have a lot of regulatory controls in place. So there are, you know, it's not like, again, like you can turn around tomorrow.

Someone say, I am interested in this and let me just start doing research on this tomorrow. It takes a lot of time and energy and effort to get through these regulatory challenges in order to even be able to start testing it. And so that's probably one of the reasons that contributes to and where we are with our understanding of psilocybin is these, these schedule one.

Um, regulatory challenges are significant and they're high, so that creates this kind of barrier for how easy it is to, to do these types of studies. Um, so that's one of the reasons why I think we just don't know enough about psilocybin yet. And again, it's being that it, what it's known for is its hallucinogenic impacts most of everything.

We know really 99% of what we know about it. Is what it does in the brain and what we know from clinical outcomes. But outside of that, very few studies have studied anything else really. Yeah. Interesting. So, um, again, big picture. I think what you're hope, just kind of give your vision on, on where you're gonna, you know, go from here in terms of like, obviously you're, you're, you've talked about, you know, looking at it as something that, again, is ultimately what you're kind of describing as a jro protective drug, right.

So when you think about scheduling that out in terms of, you know, this is what I'm gonna do next, this is what I'm gonna do next, what does that look like? Yeah. To, to enhance this? Yeah. I mean, part of what we're doing now is sifting through the, all this data that this massive amount of data that we have collected already.

Um, and trying to really understand the, the epigenetic changes that have happened in those same mice. Um, what's happening at the organ specific level? Um, separate from that, I think we really need to define the optimal treatment protocol. Um, some of our unpublished data, we are finding that like the frequency of dosing is really important, maybe as important or maybe even more important than the dose itself.

And so, um, we're finding that if you change the frequency of dosing. You have dramatically different impacts, even. Uh, so understanding the, the dosing, the optimal dosing protocols for jro protection is gonna be really important. Uh, so like what happens if you, I mean, we started with age mice, you know, that were equivalent of a 60-year-old.

But what happens if you start it the equivalent of a 40-year-old? Are you gonna have, you know, that much more benefit? Or does it not matter what happens if you give. Instead of, you know, we gave 10 doses. What happens if you give 20 doses? Are you gonna have, you know, is that gonna change efficacy? Um, again, frequency of dosing, uh, sex specific differences.

Uh, how early do you start? Is there a point at which, you know, you're beyond the point of impacts? Like, if you start at the equivalent of, you know, human, human of equivalent of 80 years old, does it, is it too late to have an impact? You know, so we need to really better understand. The optimal treatment protocols to provide GI protection.

And then I think from there, that's where I think it'll get really interesting in terms of looking at how can you use this as an intervention that could then improve age associated disease outcomes. The things that normally happen with, with natural aging or when you are injured or, you know, you don't think of this as an injury, but COVID is, is a lung injury.

You know, when you have an injury. In older age and you have this kind of jro protection behind you, or you've been doing this for a certain amount of time, can you improve those outcomes? We don't know the answer to that, but I'm really hoping that psilocybin has the potential to do that. One real quick follow up question to the dosing.

When, with regard to how much you gave the mice, for example, um, does that, was that equivalent to what you would. Call 'em microdose, uh, for humans, or are they getting high doses? Um, so we, we measure in animals, we measure, uh, psych. So we, we did know something about dosing and we actually spent a lot of time thinking about dosing when we did this study.

So one is because of prior mouse studies, we know what psychedelic dosing in mice. Generally, it looks like in terms of ranges. So we tried to, uh, we wanted to give a psychedelic dose just because I think there have been more studies with psychedelic thing versus microdosing at least, at least up until this point.

So we, we know a little bit more about clinical benefits from high dose versus nons psychedelic dosing. So we, we took a. We tried to also extrapolate a bit from what's known about those doses in clinical trials and what's known about psychedelic doses in mice. Um, the other considerations, which is why this becomes, you know, people are, are asking me a lot about how does this translate to humans and, you know, trying to make translate.

And I, you know, I warn people against doing those, those types of things at this point because one, this is the very first study ever. Um. This study needs to be validated, not just by our lab, but by outside labs, that that needs to happen. But also, you know, there's so many considerations that go into dosing.

Like mice have, uh, their metabolism is like four times faster than humans, right? So, so if you give, if you, if you think about it like it's not apple's. It's apples to oranges when you're thinking about like metabolism. And so we actually gave a higher dose in mice to account for the fact that it's so rapidly, um, metabolized in mice compared to humans.

So it's, the dose regimen was, uh, something that we determined from a number of different things from taking, you know, understanding what is a psychedelic dose. In mice. What, what's a psychedelic dose in human patients? Try and come up with a dosing regimen that, um, would be somewhat comparable and then, you know, uh, metabolism and things like that.

So again, it's not ready for direct human translation. Uh, lot more needs to be done in terms of that. And, and then another thing that goes with that is the long-term potential harms. We don't know anything about, you know, most of the, the studies that are in clinical trials. Are like one or two, you know, high dose, um, treatment protocols.

Uh, I don't know of a study. There may be, but I don't know one off the top of my head where they've given a repeated dosing of psilocybin over a long period of time in human patients that we, we know nothing about the safety of that actually. So we have to think about, um, when we think about clinical translation, not only do we have to identify what's, you know, optimal.

For efficacy and jro protection, but we also have to take a much closer look at potential harms. You know, does this have, you know, when you think about, you know, uh, improving cellular lifespan and, uh, cellular dividing war, the first thing that, you know, one might think of is, well, could this have a potential?

Um, risk, higher risk for cancer. We don't know. Um, there are some like correlative studies out there showing that, that suggest that, um, psilocybin people that have taken psilocybin have less cancer risk. But again, this like rigorously tested this, were, these are like correlative studies. Um. And, and again, the reality is no one's really ever tested repetitive, long-term dosing, especially in the context of aging and what the potential harms of that are.

So we would need to really rigorously test that and define that, make sure this is a safe treatment. Fascinating stuff. Uh, uh, I wanna thank you so much for being on the show, Dr. Hecker. And, you know, good luck with this. Certainly be keeping an eye out to see what you guys are coming up with. Thanks so much.

Thanks a lot. Thanks for listening. A quick reminder that while I am in fact a surgeon, nothing I say should be construed as medical advice. Now, make sure to include your physician in any medical decisions you make. And also if you're enjoying the show, please make sure to show your support with the like, share, or subscribe.