00:00Welcome to The Deep Dive, the show where we try to unpack some complex science and make it really accessible.

00:06Today's Deep Dive is proudly supported by RevGenetics, and we're jumping into something, well, pretty surprising today, a study that looks at psilocybin.

00:16Yeah, that's psilocybin, but maybe not in the way you're thinking.

00:19It's about its potential to actually extend cellular lifespan, even improve survival in older mice.

00:27Yeah, it's fascinating stuff.

00:28This was published with the Japanese Society of Anti -Aging Medicine.

00:31Right, so we're moving beyond the usual talk about its effects on the brain and into, well, longevity itself.

00:37Let's get into it.

00:39Okay, so most people hear psilocybin and they immediately think mental health, right?

00:45anxiety, addiction, maybe even Alzheimer's research.

00:48and there's solid clinical evidence for that potential.

00:51It seems really powerful for some people.

00:52Definitely.

00:53The effects can be profound, sometimes even from like a single dose, but the how, the actual molecular nuts and bolts behind those benefits, especially outside the brain, has been a bit of a black box.

01:05Right. Most studies just focus on the neurological side.

01:08So this new study kind of steps back and asks a, well, a much wider question.

01:13They introduced this idea called the psilocybin telomere hypothesis.

01:17Telomeres.

01:18Okay, those are the protective caps on the ends of our chromosomes, right?

01:21They shorten a cell's age.

01:23Precisely. Think of them like the little plastic ticks on shoelaces.

01:27They protect the important stuff, your DNA.

01:29Every time a cell divides, they get a bit shorter. Eventually, they get too short and the cell stops dividing.

01:34It goes into senescence.

01:35That's, you know, a key part of aging at the cellular level.

01:38Okay, I follow that.

01:40psilocybin, how does that connect to telomeres?

01:43That seems like a big leap.

01:44does, but here's the link they explored.

01:47We know our mental state can influence telomere length.

01:50like chronic stress, anxiety, depression, they're associated with faster telomere shortening.

01:56so bad mental states, faster aging at the cellular level.

01:59Kind of, yeah.

02:01And conversely, positive mental states seem to correlate with longer telomeres.

02:05So the researchers thought, well, psilocybin seems pretty good at improving those negative states.

02:09Right. Could it directly impact the telomeres themselves?

02:12Could it actually influence biological aging through that pathway?

02:16Nobody had really tested that before.

02:18Okay, so from mood improvement to actually changing the aging clock in our cells, that's ambitious.

02:24How did they even start to test that?

02:26They started small in the lab with in vitro studies using human cells.

02:31And they used psilocin, actually.

02:33Psilocin. Yeah, that's the active form.

02:34It's what psilocybin breaks down into in your body. It's the molecule that actually does the work.

02:39Got it. So testing the active compound, what happened in those human cells?

02:43The results were pretty striking.

02:45used standard cell types for aging research, human fetal lung fibroblasts, and also adult human skin fibroblasts.

02:54And psilocin treatment significantly extended the lifespan of these cells.

02:58lifespan.

02:59Like, they just kept dividing longer.

03:01Exactly. They just kept going for much longer than the untreated cells.

03:04How much longer are we talking?

03:05Like, a little bit, or?

03:06Well, in the lung cells, a 10 micromolar dose pushed the lifespan out by 29 percent. But at 100 micromolars, it was a 57 percent extension.

03:1657 percent in human cells.

03:19And even in the adult skin cells, the 100 micromolar dose gave a 51 percent boost.

03:24Okay, hold on.

03:2557 percent longer lifespan for cells in a dish.

03:30That's huge, isn't it?

03:32What was happening inside the cells?

03:34They saw a whole shift.

03:35Psilocin basically delayed the cells from hitting that wall, replicative senescence.

03:41divided more times overall.

03:42That's the cumulative population doublings. And they divided faster, or rather, the time it took them to double decreased.

03:49So, healthier, more active cells for longer. Not just surviving, but thriving.

03:53That's a good way to put it.

03:54And when they looked at the molecular markers, it backed this up.

03:57Okay, what did they see there?

03:58They saw less of the stuff you associate with aging cells, lower beta -galactosidase activity.

04:03That's a common aging marker.

04:05And lower levels of proteins that stop cell division, like P21 and P16.

04:09So, less stop signals.

04:11Right. And at the same time, more go signals, more markers of proliferation, like PCNA. It really looked like the cells were, well, more youthful.

04:19It sounds like it.

04:20Do they pinpoint any key regulators making this happen? Yes, and this is a big one.

04:24They found elevated SIRT1.

04:28SIRT1, that's one of those longevity -length proteins, right?

04:31Involved in stress response, metabolism.

04:33Exactly. It's like a master regulator for cellular health and resilience.

04:37Seeing SIRT1 go up is a really important clue connecting psilocin to these anti -aging effects.

04:43Okay, SIRT1 up.

04:45What about oxidative stress?

04:46That's always a big factor in aging.

04:48They looked at that too.

04:49And they found significantly less oxidative stress.

04:53And it was dose -dependent, more psilocin, less stress.

04:57How does that work?

04:58It seems linked to lower levels of Nox4.

05:00That's an enzyme that generates damaging oxidants and higher levels of Nrf2.

05:05Nrf2 is basically the master switch for the cell's antioxidant defenses.

05:10So less damage being produced and better defenses against it?

05:13That would certainly help the cells stay younger. You'd think so, yeah.

05:16Less DNA damage, better overall protection. Okay, so SIRT1, oxidative stress. But what about the original idea, the telomeres?

05:23Did they actually measure them?

05:25They did, and this was crucial.

05:26They compared psilocin -treated cells with untreated cells of the same age that had become senescent.

05:32And the telomeres in the treated cells were preserved.

05:35They were longer.

05:36So actual physical evidence?

05:39It supports the hypothesis?

05:41It's the first experimental evidence backing that psilocybin -telomere hypothesis, a direct link observed in the lab.

05:48Pretty significant.

05:49Absolutely.

05:50So, okay, in a dish, longer cell life, preserved telomeres, less stress, more vitality markers.

05:57It's compelling.

05:58But the big question is always, does this translate to a whole animal, a living being?

06:02Right, the essential next step.

06:04So they moved to in vivo studies using mice, aged female mice specifically.

06:09were 19 months old.

06:10Which is like, what, in human years?

06:12Middle -aged?

06:13Older, equivalent to maybe 60, 65 years old in human terms, so definitely getting up there. And what do they do with these older mice? They gave them psilocybin, once a month for 10 months.

06:23Once a month, for almost a year of their remaining lifespan.

06:26Okay. What happened?

06:27The survival results were, well, quite stark.

06:31The mice that got psilocybin had an 80 % survival rate over that period.

06:3580%. And the control group, the ones that didn't get it?

06:38Only 50 % survived.

06:39Wow.

06:4080 versus 50.

06:42That's a massive difference in survival.

06:43It really is a very significant increase in lifespan for these aged mice.

06:47Do they look any different?

06:49Could you see any outward signs?

06:51Yes. They mentioned phenotypic improvements.

06:54Basically, the psilocybin mice looked healthier.

06:57Better fur quality, more hair growth, less white hair, visible signs that they were aging better.

07:03not just living longer, but potentially healthier while doing it.

07:06Looking younger, even.

07:08Seems that way.

07:09It points towards a systemic effect, not just something hidden away inside the cells. So how do we connect the dots here?

07:15The cell stuff, the telomeres, SIRT1, less stress, and then these mice living longer and looking better, what's the proposed mechanism?

07:22The study suggests psilocybin is hitting signaling pathways tied directly to cellular aging.

07:27It's delaying that senescence, boosting lifespan.

07:30And they point towards the 5-HT2A receptor.

07:33That's the main receptor psilocybin interacts with in the brain for its psychedelic effects, right?

07:38It is. But here's the key.

07:40That receptor isn't only in the brain.

07:42It's found in lots of other cell types throughout the body.

07:46Previous research has actually shown that activating this receptor can boost SIRT1 expression and antioxidant enzymes, which fits with what they saw here.

07:57Elevated SIRT1 and reduced oxidative stress.

08:00The same receptor, but triggering these longevity pathways in other cells via SIRT1 and antioxidant responses.

08:07That seems to be the leading idea.

08:09It's a really neat connection between the known neurological target and these newly discovered systemic aging effects.

08:15It's amazing how these biological systems are intertwined.

08:18A compound known for one thing turns out to have these, well, deeper potential roles.

08:23And you know, that's exactly the kind of thing that makes this field so exciting.

08:26It deepens our whole understanding.

08:28That is why the team at RevGenetics focuses on researching unique compounds like fisetin, tetrahydrocurcumin, and resveratrol.

08:35They've been doing that since 2007.

08:37It's exciting to see studies like this discovering more about how nature's medicine cabinet is just so vast.

08:42You know, so much potential for health and longevity still being uncovered.

08:46It really is.

08:47And RevGenetics' commitment to science -backed health education fits right in with what we try to do here on the Deep Dive. It's about sharing that journey of discovery.

08:56Okay, so stepping back.

08:58This is pretty groundbreaking, isn't it?

09:00You said it's the first experimental evidence showing psilocybin hitting multiple hallmarks of aging.

09:05That's right.

09:06Delayed senescence, preserving telomeres, better DNA stability, less oxidative stress.

09:12It ticks a lot of boxes associated with aging. So what could this mean down the line for, know, aging research or even therapies?

09:20the implication is that psilocybin could potentially be what they call a disruptive pharmacotherapy.

09:25eruptive meaning.

09:26Meaning something new, potentially game-changing. A novel, geroprotective agent.

09:30Something that actively helps us age healthier.

09:33Or maybe even a therapy for specific age -related diseases.

09:36It opens up a whole new direction.

09:38And the fact that it worked, even when they started treating the mice late in life, that seems really significant for humans.

09:46It really does.

09:46Because often you wonder if you need to start interventions super early.

09:50This suggests maybe not.

09:52Maybe there's benefit even later on.

09:54And is it feasible for older adults?

09:57Well, thinking about safety, there was that clinical trial where people up to 70 years old took psilocybin with no serious issues.

10:05And the FDA has given it that breakthrough therapy status, which suggests a decent safety profile.

10:10So yeah, it looks potentially feasible.

10:13Okay, sounds incredibly promising.

10:15But you know, with exciting early findings, there are always caveats, right?

10:19we still need to figure out.

10:20Oh, absolutely.

10:21The study authors are very clear about that. need more research to figure out the best way to use it.

10:26What's the optimal dose?

10:27How often?

10:28When should treatment start?

10:29Would earlier be even better?

10:31Lots of practical questions remain.

10:32Makes sense. What about differences between people?

10:35Or, well, sexes.

10:36That's another key point.

10:37This mouse study only used females just to keep things simpler initially.

10:42But we definitely need studies looking at males too to see if the effects are the same or different.

10:47Biological sex can matter a lot in how therapies work.

10:50Good point.

10:51Now, you mentioned delaying senescence.

10:55Does that raise any concerns about cancer?

10:58Senescence is sometimes seen as a safety mechanism against uncontrolled cell growth.

11:03That's a really important consideration.

11:05And the researchers highlight it.

11:06Their cell studies didn't show any signs of the cells turning cancerous, which is good. Okay.

11:10But they strongly emphasize the need for long -term studies in animals specifically looking at cancer risk.

11:16If you suppress a natural anti -cancer mechanism like senescence over the long term, you absolutely have to rigorously check if that has any unintended consequences regarding cancer.

11:27It's a critical safety check needed for sure.

11:29Thorough long -term safety assessment is key. What about the underlying science?

11:33Are all the molecular details worked out?

11:35Not completely.

11:36We need more work to pin down exactly how it's all happening.

11:39Is it all through that 5 -HT2A receptor or are there other pathways involved?

11:44And what about epigenetics?

11:46Things like chromatin changes or DNA methylation, these can alter gene activity without changing the DNA code itself.

11:53They might play a role too.

11:55Still more digging to do there.

11:57So lots of scientific questions still open. Yeah.

12:00And what about just doing the research?

12:02Are there hurdles there?

12:03Unfortunately, yes.

12:05The paper mentions the ongoing challenges.

12:07Psilocybin is still a scheduleized substance in many places, which makes research complicated and expensive.

12:13And getting federal funding for this kind of work has been historically difficult.

12:17These are real -world barriers that can slow down progress.

12:20Despite those hurdles though, the overall feeling seems pretty optimistic.

12:24I'd say so. Very optimistic, but grounded.

12:26These are early results, yes, but they're incredibly exciting.

12:29They genuinely open up a whole new way of thinking about psilocybin and its potential impact, stretching way beyond the mind and into the fundamental processes of aging itself.

12:38so let's try to wrap this up.

12:40Our deep dive today really uncovered something unexpected, didn't it?

12:44How psilocybin, this compound we mostly associate with mental effects, might actually hold some keys to making cells live longer and promoting overall longevity.

12:55It really challenges how we think about aging.

12:57And we want to thank RevGenetics again.

12:59Their support makes these kinds of explorations into cutting -edge science possible. They're really committed to sharing knowledge about natural compounds in health.

13:07And if you want to learn more about their mission and the science they explore, you can visit RevGenetics.com.

13:13So as we finish, it really makes you think, doesn't it?

13:16What other compounds are out there, maybe ones we've overlooked or just misunderstood, that might hold profound secrets for a longer, healthier life?

13:24Something to ponder.

13:25Join us next time for another deep dive into the fascinating world of science.