Latest / The LIVING Room Podcast | Inside The WNDR Lab / Can We Wake Up Sleeping Brain Cells? ‘Zombie Cells’ And The Aging Brain

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Can We Wake Up Sleeping Brain Cells? ‘Zombie Cells’ And The Aging Brain · The LIVING Room Podcast | Inside The WNDR Lab

• 0:00
  SPEAKER_03: I would not inject anything that someone called a stem cell into any other part of my body just because it's just unproven and hype is a real thing.
• 0:09
  SPEAKER_03: There are always gonna be people who will take information and utilize the lack of knowledge in the general population and take advantage of that.
• 0:16
  SPEAKER_03: People overpromise and overclaim a lot.
• 0:18
  SPEAKER_03: And this is something that really drives me crazy as a scientist mostly because we try very hard not to overclaim, not to overstate.
• 0:26
  SPEAKER_03: And when scientists do it, it's even more upsetting.
• 0:28
  SPEAKER_03: It feels a lot like snake oil salesmen as opposed to rigorous scientific integrity.
• 0:33
  SPEAKER_03: Some of the places out there that are doing some crazy stem cell therapies that are not FTA approved are like, I'm gonna take your fat and I'm gonna purify stem cells out of it, and then I'm gonna inject it in this thing.
• 0:42
  SPEAKER_03: It's not harmless.
• 0:44
  SPEAKER_03: There's some really terrible horror stories out there.
• 0:46
  SPEAKER_05: We do know a lot of things that can help contribute to improving or at least maintaining brain function now.
• 0:52
  SPEAKER_03: I mean, just trying to understand how different parts of the brain talk to each other sounds simple, but it's so difficult in a human to understand.
• 0:59
  SPEAKER_05: That's why aging is so difficult to study.
• 1:01
  SPEAKER_03: Oh yeah.
• 1:02
  SPEAKER_03: Do you want to do a clinical trial on aging humans?
• 1:04
  SPEAKER_05: What are the proposed mechanisms by which we can actually elicit neurogenesis?
• 1:08
  SPEAKER_03: Obviously, we have things that can increase neurogenesis.
• 1:10
  SPEAKER_03: We've learned a lot about it.
• 1:11
  SPEAKER_03: One is alive.
• 1:24
  SPEAKER_05: Darcy, welcome.
• 1:26
  SPEAKER_05: It's such a privilege to have you here.
• 1:28
  SPEAKER_03: Thank you.
• 1:29
  SPEAKER_05: So I would like to start right at the very top with a definition.
• 1:35
  SPEAKER_05: I think the words stem cells are pretty divisive for people.
• 1:39
  SPEAKER_05: I think there's two camps.
• 1:40
  SPEAKER_05: Correct me if you think I'm wrong.
• 1:43
  SPEAKER_05: Some people, when they hear the word stem cells, they think of some miracle solution, medicine, treatment to a any number of problems.
• 1:52
  SPEAKER_05: And then some people I think probably think controversy, right?
• 1:55
  SPEAKER_05: That they're like overreaching, overselling.
• 1:58
  SPEAKER_05: Can you maybe start by giving us your perspective?
• 2:01
  SPEAKER_05: You know, what even is a stem cell for people that aren't aware?
• 2:04
  SPEAKER_03: Yes.
• 2:05
  SPEAKER_03: So so people know them, I think, often because of the embryonic stem cell controversies that kind of happened during the Bush years.
• 2:12
  SPEAKER_03: And and so the idea is that you have a cell that can self-renew, it can make more of itself, and that it can make other things.
• 2:22
  SPEAKER_03: And so there's many different types of stem cells.
• 2:24
  SPEAKER_03: So we don't have any right now that have the ability to make an entire organism, all the cells of an entire organism, and the placenta as well.
• 2:34
  SPEAKER_03: That's not impossible right now, but we do have some that can make any cell in the body, and those we have, we say that they have a certain amount of potency, so pluripotency.
• 2:44
  SPEAKER_03: They can make all of the cells of the body.
• 2:46
  SPEAKER_03: And so those are things like human embryonic stem cells that were taken from, you know, uh donated uh in vitro fertilization um uh blastocyst, and they took the cells out and then they expanded them.
• 3:01
  SPEAKER_03: I mean, they're still expanding today.
• 3:03
  SPEAKER_03: So these are kept in a repository, these lines.
• 3:05
  SPEAKER_03: So those are really useful if you want to make any cell type of the body and you want to study a human heart cell, you want to study a human skin cell.
• 3:15
  SPEAKER_03: And so this actually opened up research quite a lot.
• 3:18
  SPEAKER_03: There was a sacrifice of a few blastocysts that came from in vitro fertilization that would have been thrown away, but it was still worth the entire enormous gains, I think, that came.
• 3:28
  SPEAKER_03: Now there's another type of cell that can make any type of cell of the body.
• 3:32
  SPEAKER_03: Those people call IPSCs or induced pluripotent stem cells.
• 3:37
  SPEAKER_03: These are more recent, and people like these because there's less controversy about them.
• 3:42
  SPEAKER_03: And that's where you take a sample from a person, maybe a skin punch or something from the blood, right?
• 3:49
  SPEAKER_03: And you can put a certain type of factors in there.
• 3:52
  SPEAKER_03: You kind of reprogram them, um, and then they revert back to a stem cell stage.
• 3:59
  SPEAKER_03: And then they also can make any cell of the body.
• 4:02
  SPEAKER_03: And that's really useful in research because we can take it from someone who has a mutation for a disease.
• 4:08
  SPEAKER_03: For example, if you have an Alzheimer's disease mutation, and then I can take those and I can then turn them into stem cells, and then I can turn them into neurons.
• 4:17
  SPEAKER_03: And now I can study your neurons with your mutations exactly in a dish.
• 4:22
  SPEAKER_03: In a dish, obviously, right?
• 4:23
  SPEAKER_03: We're doing this all in vitro, is what we call that.
• 4:26
  SPEAKER_03: So those are kind of the ones that have a lot of power in research.
• 4:30
  SPEAKER_03: Uh, people like to think of transplantations, you know, as you know, a Parkinson's disease patient.
• 4:36
  SPEAKER_03: There are clinical trials now where they transplant stem cells that have been turned into uh uh cells that we call progenitors, like they're about to become a dopaminergic neuron, which is what's lost in those patients and being transplanted in.
• 4:50
  SPEAKER_03: And since this is a regional loss of neurons, you can put those in, they'll turn into neurons, and you can gain some function back.
• 4:56
  SPEAKER_03: So this is happening now.
• 4:58
  SPEAKER_03: So stem cells have a lot of power from that, from that aspect of things.
• 5:02
  SPEAKER_05: On on the the Parkinson's transplant, I believe in Japan, haven't they, they just had their equivalent of FDA approval for for that process?
• 5:11
  SPEAKER_03: So I I I think in Japan there's also just this consortium all around the world of people who are doing clinical trials for this.
• 5:18
  SPEAKER_03: And so there are some that are um in um in Wal Cornell, for example, Lorenz Studer is running one.
• 5:26
  SPEAKER_03: And there's multi, there's one in Sweden, actually, Malin Parmer had one.
• 5:29
  SPEAKER_03: So I do know that they're all kind of talking to each other, and then they have meetings where all the people doing these clinical trials can see where things are.
• 5:37
  SPEAKER_03: Um, there also was some work that was done in Madison.
• 5:39
  SPEAKER_03: So I'm from UW Madison, and this is actually internationally renowned for stem cell research because Jamie Thompson was the one who isolated the first human embryonic stem cells and also co-published the first induced pluripotent stem cells with humans as well.
• 5:54
  SPEAKER_03: So this is also where the can um the Y cell, which is where you store all of these lines uh from all over the world, all these patient lines, this is where the repository is as well.
• 6:05
  SPEAKER_03: So it's uh it's just very well known in why I was drawn also to Madison.
• 6:10
  SPEAKER_03: Um and they just had, because you know, there's a primate center, and you know how you may or may not agree with that type of research, but they were able to see that if you took cells from your own sample, turned them into stem cells, and then put them in, that you had a much better result and survival of those cells than if I took anybody's cells, right?
• 6:30
  SPEAKER_03: So autologous transplantation actually had much better integration and function at the end.
• 6:36
  SPEAKER_03: So there's a lot of really exciting work happening with that.
• 6:39
  SPEAKER_03: But that's all thinking about this embryonic context, because these are all, as soon as you revert to this stem cell state, these are all basically fetal cells.
• 6:47
  SPEAKER_03: So there is limitation in studying them in an aging context because they don't have age.
• 6:52
  SPEAKER_03: They are fetal in age.
• 6:54
  SPEAKER_05: Yeah, yeah.
• 6:54
  SPEAKER_03: So my work very quickly.
• 6:58
  SPEAKER_05: Owen, yes, goodness me, mid-conversation.
• 7:02
  SPEAKER_05: Don't cut this out.
• 7:03
  SPEAKER_05: We have to see what we have to deal with behind the scenes here.
• 7:07
  SPEAKER_05: Never ends.
• 7:08
  SPEAKER_05: And actions.
• 7:09
  SPEAKER_03: Yeah.
• 7:10
  SPEAKER_03: So the cells that my lab studies are also are endogenous stem cells in our bodies in the adult.
• 7:16
  SPEAKER_03: And this is quite different as well.
• 7:18
  SPEAKER_03: And we have stem cells all over our bodies right now, even in my aged condition, slightly aged condition.
• 7:25
  SPEAKER_03: Um, and that's how we have, you know, our gut, right?
• 7:28
  SPEAKER_03: That's a very high turnover area stem cells in our skin, for example, our blood.
• 7:32
  SPEAKER_03: These are very high turnover.
• 7:34
  SPEAKER_03: The stem cells are making new cells all the time.
• 7:36
  SPEAKER_03: And then you have low turnover areas like muscle, um, where those stem cells don't get activated until there's some type of injury.
• 7:44
  SPEAKER_03: Um, they basically get ripped out of their the area in which they they live.
• 7:49
  SPEAKER_03: Um, and then they can actually start trying to replicate, et cetera.
• 7:52
  SPEAKER_03: And in the brain as well, and this there's also some controversy with this aspect in the brain, but in the brain, there are stem cells there as well in a region called the hippocampus.
• 8:02
  SPEAKER_03: This is an area important for learning and memory.
• 8:04
  SPEAKER_03: This is all you kind of need to know.
• 8:06
  SPEAKER_03: And and these are very low turnover, kind of maintaining homeostasis or being uh activated in response to injury.
• 8:12
  SPEAKER_03: But these are in an adult body.
• 8:14
  SPEAKER_03: So they're quite different types of stem cells.
• 8:17
  SPEAKER_03: Um, and and then also they're quite different potencies, what they can make, because the ones in my brain can only make cells of the brain.
• 8:27
  SPEAKER_03: The ones in my muscle will only make muscle, right?
• 8:31
  SPEAKER_03: The ones in my blood will only make blood lineage.
• 8:34
  SPEAKER_03: And so I think that's sometimes where some of the problems come.
• 8:38
  SPEAKER_03: There's one related to age and you know, for transplantation, for study, et cetera, is what about stem cells and age.
• 8:45
  SPEAKER_03: And the other is this idea of um what can they make?
• 8:50
  SPEAKER_03: And so, you know, some of the places out there that are doing some crazy stem cell therapies that are not FDA approved are like, I'm gonna take your fat and I'm gonna purify stem cells out of it, and then I'm gonna inject it in this thing.
• 9:02
  SPEAKER_03: And you're like, well, what stem cells could potentially be there are only gonna make these certain things.
• 9:08
  SPEAKER_03: Is that a good idea to put those into this place?
• 9:11
  SPEAKER_03: And likely it it may not be.
• 9:13
  SPEAKER_03: So so I think it's very hard to understand all those in, you know, those pieces and parts if you haven't done a lot of you know research into it.
• 9:22
  SPEAKER_03: But there are a lot stem cells, is not just kind of one thing.
• 9:25
  SPEAKER_03: There are so many elements of it, and they have lots of different potentials for research, for transplantation, for improving the our function as adults.
• 9:33
  SPEAKER_03: So it's a wide range.
• 9:35
  SPEAKER_05: That's a listed more questions.
• 9:37
  SPEAKER_03: Okay, let's go.
• 9:38
  SPEAKER_05: I'm gonna ask you one that's probably kind of naive.
• 9:41
  SPEAKER_05: You mentioned that, you know, the certain stem cell can make certain things, you know, typically where it has um originated from.
• 9:49
  SPEAKER_05: How then are you reversing the you're you know, like creating this sort of primordial stem cell from one blood cell and turning it into any organoid of the body?
• 10:00
  SPEAKER_03: It's a super question.
• 10:02
  SPEAKER_03: So um the finding that was so important that happened to um with uh Yamanaka and Thompson, kind of at the same time, published the same at the same time, was that if you take certain pieces of DNA and you make and you put it into a cell so that that cell that might normally not make the, you know, use that DNA to make protein now has it and starts making uh these proteins, that they will go in, modify the DNA and the chromatin.
• 10:31
  SPEAKER_03: And this is just a way to say all the things attached to that DNA, open and close things differently, and then allow it to kind of go back to it's almost like erasing, kind of erasing its identity back to the beginning again.
• 10:43
  SPEAKER_03: And the only way you can do it, there's been some protocols that suggest you can do this with chemicals, but the most tried and true and reproduced throughout the world is by over-expressing these Yamanaka factors, which just means making them make a bunch of things that they didn't have before by inserting new DNA code, and usually transiently, so it's not long-term there, but just like for a little bit make this and it erases everything, and you go back into the stem state state, and and then that's how you get the kind of the ones that can make all the cell types of pluripotents.
• 11:16
  SPEAKER_05: You want to rule them all, you can you can create anything.
• 11:19
  SPEAKER_03: Yes, exactly.
• 11:20
  SPEAKER_05: Interesting, yeah.
• 11:21
  SPEAKER_05: I mean, it sounds incredibly exciting, but it also sounds like something that they're that could be sort of a thread of science that people are really overreaching with.
• 11:30
  SPEAKER_05: And I don't mean that as in like there's not real science, I mean whenever we see something as sort of future sounding as as you know, growing an organ in a dish, or you, you know, a clone of you, yeah, you tend to see some overreach.
• 11:47
  SPEAKER_05: I'm not gonna name names, but I feel like it has to be said that there is a a very famous or infamous biohacker right now who just posted, you know, I've created a baby version of myself and will be able to harvest organs and you know, test against all of these different um signatures of aging.
• 12:06
  SPEAKER_05: And it's a a picture of him posted with a picture of a baby, right?
• 12:11
  SPEAKER_05: And and I think for someone has a line in many, many metals, okay.
• 12:15
  SPEAKER_05: And and what what I know that he is talking about is a uh uh induced pluripotent stem cell, right?
• 12:21
  SPEAKER_05: And so I think as a consumer, right, I I I don't, you know, I have the privilege of being able to talk to people about these things, but from the outside looking in, that sounds insane for a start, but also it sounds like he's getting something that none of the rest of us can access.
• 12:40
  SPEAKER_03: So I don't know his specific situation, but there are ways to make clones of yourself that have been there since Dolly.
• 12:47
  SPEAKER_03: I don't know if you would remember Dolly the sheep, right?
• 12:49
  SPEAKER_03: And that was nuclear transfer.
• 12:50
  SPEAKER_03: So there are other ways to do it that don't require stem cells, but more likely what's happening is that you can take those stem cells and you can make not perfect, but what we call organoids, which have some types of um, I mean, for example, intestinal organoids.
• 13:08
  SPEAKER_03: Um, these obviously are something you can grow in a dish from an from an intestinal, uh, from an induced pluripotent stem cell.
• 13:15
  SPEAKER_03: You put in certain factors that we've learned about through development, because that basically all you're doing is you're trying to mimic development.
• 13:22
  SPEAKER_03: What kind of molecules would these cells see if they were going to become this type of cell?
• 13:26
  SPEAKER_03: But this is not an intestine like we have in our body, right?
• 13:30
  SPEAKER_03: It's like these very tiny little things with, you know, little outcroppings, and there's many areas, you know, that you can study.
• 13:37
  SPEAKER_03: But this might be, you know, what's happening there.
• 13:40
  SPEAKER_03: The same might be true for a kidney, for example.
• 13:43
  SPEAKER_03: This, I mean, e with with um brains, the organoids that are brains, they don't have all the regions of the brain.
• 13:49
  SPEAKER_03: They don't even have the larynx, they don't, they they're very variable.
• 13:53
  SPEAKER_03: So sometimes they just, I mean, they don't look like anything.
• 13:57
  SPEAKER_03: So um, but one could say, I'm making all these types of organs, uh, if you didn't, you know, what know what you're doing.
• 14:07
  SPEAKER_03: But yeah, uh, I think there will always be some people who take the technology and do crazy things with it.
• 14:16
  SPEAKER_05: Yeah.
• 14:16
  SPEAKER_05: But that is not even possible, the crazy things that he's saying right now.
• 14:20
  SPEAKER_05: Uh as far as I'm now.
• 14:22
  SPEAKER_03: I mean, no, I mean we don't, first of all, we can't to have a a baby in this case, right?
• 14:29
  SPEAKER_03: You would have to be able to have a placenta to, you know, support said baby.
• 14:33
  SPEAKER_03: And we don't have today potent stem cells currently.
• 14:37
  SPEAKER_03: There are not really protocols.
• 14:38
  SPEAKER_03: People are playing around with it, but there's not really protocols that can do that.
• 14:42
  SPEAKER_03: So that's one level up from what I said, which is pluripotent.
• 14:46
  SPEAKER_03: I can make all the cells of the body, but to make the placenta as well is one level up, and we really just don't do that.
• 14:52
  SPEAKER_03: And also there are ethical considerations to that, which is why it's you know, this has been people have thought a lot about this as well.
• 15:01
  SPEAKER_03: There are there is uh the international stem stem cell, it's ISSCR.
• 15:06
  SPEAKER_03: I can't, I don't remember all of the things, but this is now the organization that the scientists themselves have come together also to make guiding principles on on what we do with those things.
• 15:15
  SPEAKER_03: But it's not really possible to make a baby without having a placenta, and we can't do that, right?
• 15:21
  SPEAKER_03: So I I it it's more likely you could do nuclear transfer uh in the same way Dolly, if you were trying to do that, but it's also just scary the whole discussion in general.
• 15:32
  SPEAKER_05: Right.
• 15:32
  SPEAKER_03: It's very scary.
• 15:34
  SPEAKER_05: What do we think is is going to be, you know, I I assume a lot of that was maybe, maybe, maybe not tongue in cheek, but like just the play on words um for having created various different tissues of different organs in vitro that one day you could test, you know, um drugs against, which which we can do now, right?
• 15:56
  SPEAKER_05: And so that's probably really what's happening.
• 15:58
  SPEAKER_05: Yeah, but but how how far away are we from 3D organ printing, from being able to take those and actually create something that works systemically?
• 16:08
  SPEAKER_05: It feels like that would be a huge like frontier for organ replacement, which is of often a failure, right?
• 16:17
  SPEAKER_03: Yeah, I think people are trying this.
• 16:18
  SPEAKER_03: I mean, that um one of the colleagues I know has tried, you know, bioprinting layers of brain because there's many different layers.
• 16:26
  SPEAKER_03: The problem is that it's so complicated.
• 16:29
  SPEAKER_03: There's many different cell types.
• 16:31
  SPEAKER_03: You have vasculature running in there, you have things that come from outside.
• 16:35
  SPEAKER_03: For example, you know, in our brain, we have microglia in there.
• 16:39
  SPEAKER_03: This is the immune cells of our brain.
• 16:41
  SPEAKER_03: They are important, um, but they don't actually originate from the brain, they originate from something called the yolk sex.
• 16:47
  SPEAKER_03: So they have a totally different origin.
• 16:49
  SPEAKER_03: So, how would you develop that when it has to come and migrate in from somewhere else?
• 16:54
  SPEAKER_03: And so I think the complicated piece is that any organ requires so many different cells to be interacting together, plus you know, vasculature, neuronal input, things like this.
• 17:08
  SPEAKER_03: And I think it's great.
• 17:10
  SPEAKER_03: I think we should be working towards that.
• 17:12
  SPEAKER_03: But other people are have started investing more in trying to make you know pigs less immunogenic and just taking uh you know parts of a pig uh to replace, for example, thinking that that's maybe further ahead.
• 17:24
  SPEAKER_03: Um, and some tissues may be easier than others, uh, you know, depending on the complexity.
• 17:30
  SPEAKER_03: Um things, you know, right now I science moves slowly.
• 17:35
  SPEAKER_03: So I think putting numbers to anything, you need to add like another 20 to whatever value you would generally say, because we want to be comfortable with uh with what we see at the end, right?
• 17:49
  SPEAKER_03: We are we don't want to have a high amount of risk in moving anything into a patient scenario.
• 17:53
  SPEAKER_05: Safe and effective is exactly safe and effective.
• 17:57
  SPEAKER_03: But yeah, I would be hesitant to actually put any numbers, but I would say we're not that close right now.
• 18:03
  SPEAKER_05: I could only imagine that things like skin and muscle are infinitely less complicated than brain.
• 18:09
  SPEAKER_03: Yes, I mean brain is for me the last frontier.
• 18:12
  SPEAKER_03: It's one of the things that kind of drew me to this area.
• 18:14
  SPEAKER_03: There's so much we still do not know.
• 18:17
  SPEAKER_03: And and uh I think before you can even try to replicate it, you have to understand much more about how everything works together.
• 18:24
  SPEAKER_05: Can can I ask you a question?
• 18:26
  SPEAKER_05: With with all of that being said, you know, what are we able to use these to study?
• 18:31
  SPEAKER_05: You know, what are we what what's the the benefit of being able to you know create functional tissue in a dish or or working tissue?
• 18:40
  SPEAKER_03: So I mean, I think just kind of like I mentioned before, for research, being able to get your hands on human tissue is a big difference.
• 18:48
  SPEAKER_03: We you know, we use a lot of rodents still, yeah, yeah.
• 18:51
  SPEAKER_03: And that's great, but being able to finally look at what what the differences are in a human context is is very helpful, even if it's not in a body, right?
• 18:59
  SPEAKER_03: Even if it's just in a dish.
• 19:00
  SPEAKER_05: So that's like a bridge between the animal models and the work is systemically in a human.
• 19:06
  SPEAKER_03: Yes.
• 19:07
  SPEAKER_03: I mean, it there's a weakness to every situation, of course.
• 19:10
  SPEAKER_03: A mouse has a weakness, human cells in a dish have a weakness.
• 19:13
  SPEAKER_03: Yeah, you try to approach a scientific question in many different ways, right?
• 19:18
  SPEAKER_03: And have orthogonal approaches and say, can I see it works like this in an animal, it works like this the same way in a human cell in a dish, for example.
• 19:28
  SPEAKER_03: But the other piece that's useful is that you can study disease or even things that we don't know if there are mutations associated with it.
• 19:36
  SPEAKER_03: So if you had an autism population, for example, and you can find uh a similar um, you know, set of mutations that were associated with these certain behaviors, but you could take samples and you could start to ask about, well, what happens with these neurons when we make, you know, there are many different types of neurons.
• 19:55
  SPEAKER_03: Well, what if we make this type of neuron?
• 19:57
  SPEAKER_03: Do they look the same?
• 19:58
  SPEAKER_03: If we make this type of neuron, do they look the same compared to kind of a control, for example, and start to look at the phenotypes or the way the cells are behaving in addition, instead of only going by DNA, for example, now you can actually ask those questions.
• 20:12
  SPEAKER_03: Um you can do that with out diseases, neurodegenerative diseases, for example.
• 20:17
  SPEAKER_03: Uh, this opens up a huge amount of doors because to make an animal model for some of these diseases, it's it's somewhat impossible because they might not have the same the same effect with that gene, their mouse gene, right?
• 20:34
  SPEAKER_03: So you have to put in, you know, a human mutated version of this gene and then another human mutated, and it might take five of these, right?
• 20:42
  SPEAKER_03: It's a lot of work, forget it, right?
• 20:43
  SPEAKER_03: And then I could study a patient's samples um much, much easier, and then maybe take that back into a rodent, right?
• 20:50
  SPEAKER_05: And as our mutual friend Professor Wilmere would say, we're not just big mice.
• 20:54
  SPEAKER_03: No, we we are not just big mice.
• 20:56
  SPEAKER_03: It's true.
• 20:57
  SPEAKER_03: Yeah, it's true.
• 20:58
  SPEAKER_03: I mean, it is a model system, you know, that that I think has given us so much information, and the in the an the in-body context or the in vivo context is really important.
• 21:10
  SPEAKER_03: Yeah.
• 21:11
  SPEAKER_03: Um, so uh so as it often is, but so that piece, I think, uh that piece I think is still.
• 21:17
  SPEAKER_05: But it sounds very exciting.
• 21:18
  SPEAKER_05: I mean, like you must feel optimistic about some of these future applications.
• 21:24
  SPEAKER_03: Uh I think to be a scientist, you have to be eternally optimistic.
• 21:28
  SPEAKER_03: First of all, like 90% of your experiments fail, usually, right?
• 21:32
  SPEAKER_03: Yeah.
• 21:32
  SPEAKER_03: And you've done this one over and over and over again trying to get it to technically work, and you have to be like, okay, tomorrow, the 101st time, it's gonna work this time.
• 21:42
  SPEAKER_03: And you come back again.
• 21:43
  SPEAKER_03: So I think generally we are always optimistic about the idea that we're gonna learn something that's gonna be helpful to someone way down the road.
• 21:54
  SPEAKER_05: Hey, let me ask you then has there been anything that really stands out that was like a 101st moment.
• 22:01
  SPEAKER_05: So something that you were trying time and time again that continued to not bear fruit.
• 22:05
  SPEAKER_05: And then there was just one moment that you were discovered something amazing.
• 22:10
  SPEAKER_03: Um yeah.
• 22:13
  SPEAKER_03: Most of the moments you remember are the ones that don't work because you learn from them.
• 22:18
  SPEAKER_03: But I guess I would say in during my PhD training, I had done a big screen.
• 22:23
  SPEAKER_03: Um, and we had, I was working in the field of uh um axon regeneration, so things spinal cord injury or optic nerve injury.
• 22:32
  SPEAKER_03: And um we had had two parts to the screen.
• 22:36
  SPEAKER_03: One was everything was very blinded.
• 22:39
  SPEAKER_03: And so one was, you know, doing looking at the length of their the processes that grew from these neurons that we were looking at and modifying them in different ways and seeing which modification might change that.
• 22:52
  SPEAKER_03: And then another was to look at them, just see do they look different, do they have any unique characteristics related to their process that would be suggestive also of something interesting related to the thing we were looking for.
• 23:05
  SPEAKER_03: And my I'd been just keeping them all blinded, doing this, doing that, and as one does in their training, you're just like trying to just get through this experiment in the end.
• 23:15
  SPEAKER_03: It was like a hundred and some genes at a time where that was actually quite difficult that we were testing.
• 23:20
  SPEAKER_03: And he said, Let's just look through this.
• 23:22
  SPEAKER_03: Because I said, I think I have a hit in each of these.
• 23:25
  SPEAKER_03: Let's, and he's like, let's look and see.
• 23:27
  SPEAKER_03: And we, you know, we went through the data and he I started to, you know, dig back through.
• 23:32
  SPEAKER_03: And so it turns, okay, here's the hit that we had that's unblind it and see, you know, what was that gene?
• 23:37
  SPEAKER_03: Great.
• 23:38
  SPEAKER_03: And then he's like, well, let's look in the other two, and we unblinded it.
• 23:40
  SPEAKER_03: It was the same gene.
• 23:42
  SPEAKER_03: And it was kind of this moment where we, you know, looked at each other and we said, Oh my gosh, we were right.
• 23:47
  SPEAKER_03: This is really exciting.
• 23:48
  SPEAKER_03: This is this is something that's going to be really important.
• 23:50
  SPEAKER_03: And um, and so I I have memories of things like that.
• 23:54
  SPEAKER_05: What did that mean?
• 23:55
  SPEAKER_03: So, in that context, uh, we we were studying how you lose the ability to regenerate with age.
• 24:03
  SPEAKER_03: And in this case, it's not even with aging, it's actually happening during development.
• 24:08
  SPEAKER_03: And um, and so we were trying to see are there developmental genes that their regulation is changed, and that's why we lose this ability to regenerate.
• 24:19
  SPEAKER_03: And we ended up finding this factor that we found uh was a transcription factor.
• 24:25
  SPEAKER_03: Um, then that just means it can regulate DNA in very specific ways.
• 24:29
  SPEAKER_03: And we found that it had this very large family of 17 members, and um, and a lab nearby was had done something kind of similar in a different cell type, and they had a hit, and it was also in this family.
• 24:43
  SPEAKER_03: And no one had really looked at this any of these uh genes or this transcription factor family for the thing that we were studying, which was axon regeneration.
• 24:52
  SPEAKER_03: And we ended up being able to test all 17 and find that depending on how they were regulated during development, it was directly tied with how they would change regeneration.
• 25:03
  SPEAKER_03: And so it was actually a really exciting project, really exciting finding.
• 25:07
  SPEAKER_03: And it all started with this moment of the screen where where we unveiled, you know, the the hit from each one and we found it was the same gene.
• 25:16
  SPEAKER_03: And it was so so that is a you know something that will stick with me.
• 25:20
  SPEAKER_03: But yeah, generally we we're failing all the time.
• 25:23
  SPEAKER_03: So those were glad you kept trying.
• 25:26
  SPEAKER_03: Yes, of course.
• 25:27
  SPEAKER_05: I mean you you touched on something there.
• 25:29
  SPEAKER_05: Um, you mentioned about you know regeneration for aging, right?
• 25:34
  SPEAKER_05: And I think that is what so many people that listen to this will be curious to hear more about, specifically the domain that you've spent, you know, the majority of your career studying, which is the brain, right?
• 25:45
  SPEAKER_05: Like neuron neuronal stem cells.
• 25:48
  SPEAKER_05: Can you uh give us a like a very high-level sort of 60-second explanation of what you study at the lab?
• 25:57
  SPEAKER_05: Um, for someone who maybe isn't a scientist.
• 26:01
  SPEAKER_03: Are you setting a timer?
• 26:02
  SPEAKER_05: I'm talking about myself.
• 26:04
  SPEAKER_03: If you're not setting a timer, then I'll plus or minus five.
• 26:07
  SPEAKER_03: Okay.
• 26:07
  SPEAKER_03: So yeah, so my so my lab focuses on something called adult neurogenesis, which sounds very mystical.
• 26:14
  SPEAKER_03: Um, but to break it down, basically, the ability of stem cells in the brain to make new neurons is basically what neurogenesis is, and that that that's happening in the adult context is what we're looking at.
• 26:26
  SPEAKER_01: Yeah.
• 26:27
  SPEAKER_03: Um, I mentioned where this is happening.
• 26:29
  SPEAKER_03: This is in the area important for learning and memory in the hippocampus.
• 26:32
  SPEAKER_03: And exclusively?
• 26:34
  SPEAKER_03: Well, if we that's a that's a harder conversation to have only because well one that will go over my head.
• 26:40
  SPEAKER_03: Yeah, well, I mean, there's like species differences uh in where they are located.
• 26:44
  SPEAKER_03: There's also controversy on in humans, you know, if and when and where.
• 26:49
  SPEAKER_03: So, and I'm happy to get into all of those, but no, we'll cut that bit.
• 26:55
  unknown: Okay.
• 26:56
  SPEAKER_03: Then uh then you're taking my time as my six.
• 26:59
  SPEAKER_03: The hippocampus, you say.
• 27:01
  SPEAKER_03: Yes.
• 27:02
  SPEAKER_03: So um, yeah.
• 27:03
  SPEAKER_03: So in this region, we are really studying the rate limiting step of this whole process of making new neurons.
• 27:10
  SPEAKER_03: And that is how do you get them out of their kind of dormant, I'm not in the cell cycle stage when they're just sitting there, kind of think of like radars everywhere, waiting for signals that says, I need to divide and make some new cells.
• 27:23
  SPEAKER_03: Um, and this is what in aging, they get stuck in this stage.
• 27:27
  SPEAKER_03: And so that's why we really focus on understanding this, but they're actually very hard to study in this stage.
• 27:33
  SPEAKER_03: And the tools are not very good as well.
• 27:35
  SPEAKER_03: And they're really deep in the brain and very hard to get to.
• 27:38
  SPEAKER_03: And so um, you know, most of my work is at this basic level of even just developing new technologies to study this.
• 27:45
  SPEAKER_03: But the end result we're hoping to affect is how do I make more new neurons in this context, in an aging and in a neurodegenerative condition, where the things that they bring to our learning and our cognition are really useful and can potentially sway someone from you know being independent or not.
• 28:05
  SPEAKER_03: So bringing that cognitive resilience.
• 28:07
  SPEAKER_03: But I'm still working in my lab at this level of what do we know about the cell that needs to exit and make you know the neurons that eventually will help us get integrated into the circuitry and affect behaviors.
• 28:21
  SPEAKER_03: So if we can increase neurogenesis in adults, that is where we'll see a carryover to executive function and memory and well, so so I think I mean what's been shown in rodent, because it's we don't know yet really in human, um, is that it's things like you know, pattern separation, memory consolidation, reducing anxiety, it's uh generalization, it's um it has all these effects that are like fine-tuning.
• 28:47
  SPEAKER_00: Yeah.
• 28:48
  SPEAKER_03: Um, which maybe in someone younger, you can survive without that pretty well.
• 28:54
  SPEAKER_00: Yeah.
• 28:55
  SPEAKER_03: Now imagine that you've lost a had a lot of neuronal death, you're aged, some of these things are not working in the same way, the connectivity between regions is not the same as it once was.
• 29:06
  SPEAKER_03: Those cells could actually be the thing that can really help you over, you know, from this very poor cognition to a way to still be able to function.
• 29:18
  SPEAKER_03: We don't know a lot about it in humans, though.
• 29:21
  SPEAKER_03: So it's really hard to make this claim when we right now, I wouldn't be able to test to see how much neurogenesis you have.
• 29:28
  SPEAKER_03: And that's something that our field is really trying to work towards is finding ways to look at this in a living human in this very dark deep region with a very rare population of cells that are doing something very infrequently.
• 29:41
  SPEAKER_03: How do we measure that?
• 29:43
  SPEAKER_03: Um, and and so I think that's kind of where our field is going.
• 29:46
  SPEAKER_05: Yeah.
• 29:47
  SPEAKER_05: Is is neurogenesis in adults actually, do we know for sure that it's possible?
• 29:52
  SPEAKER_05: I've been in humans?
• 29:53
  SPEAKER_05: Right.
• 29:54
  SPEAKER_03: So yeah, so yeah, this controversy has been, you know, basically started so long ago uh by kind of the father of neuroscience.
• 30:02
  SPEAKER_03: So it's that long ago that it was controversial, where he said there are no new neurons, basically.
• 30:07
  SPEAKER_03: It's a it's a dogma.
• 30:08
  SPEAKER_03: Ramoni Cah, who was also amazing and you know, showed us a lot of images of what everything looked like in the brain at a time where it wasn't really possible.
• 30:17
  SPEAKER_03: So kudos.
• 30:18
  SPEAKER_03: Yeah, however, set made the no neurons dogma, which has kind of haunted our field for a very long time.
• 30:24
  SPEAKER_03: Um, but even you know, I I actually recently wrote a perspectives about this uh because I think it's interesting.
• 30:32
  SPEAKER_03: No matter what, every new finding, people it was like I disagree, it doesn't happen.
• 30:37
  SPEAKER_03: And then, oh, we agree, but now I don't believe the next step.
• 30:40
  SPEAKER_03: So then they tried to study it in rodents, people didn't believe it necessarily was happening.
• 30:45
  SPEAKER_03: Now everyone believes this happens in rodents, it's well understood.
• 30:49
  SPEAKER_03: Then it moved to non-human primates, mixed bag again, didn't believe it.
• 30:53
  SPEAKER_03: Now, yes, it's less than in rodents, agreed.
• 30:57
  SPEAKER_03: Um, then in humans, same thing.
• 31:00
  SPEAKER_03: So the problem with the human side of things is how do you prove a negative?
• 31:04
  SPEAKER_03: How do you prove it doesn't exist?
• 31:06
  SPEAKER_03: The absence of something.
• 31:08
  SPEAKER_03: Yeah.
• 31:08
  SPEAKER_03: Um, especially when our current technologies are things like a fixed snapshot.
• 31:14
  SPEAKER_03: Someone passes away, you get their brain, you take a section that's in that 30 microns, yeah, and then you're trying to reveal it with different antibodies, for example, or markers that are out there.
• 31:26
  SPEAKER_03: And yet, if someone uses one protocol or recipe uh versus someone who uses a different recipe, it might you might see it here and you might not see it here.
• 31:36
  SPEAKER_03: Yeah.
• 31:37
  SPEAKER_03: So there's all this technical issue that gets involved as well.
• 31:40
  SPEAKER_05: So um difficult to prove and disprove.
• 31:43
  SPEAKER_03: Exactly.
• 31:44
  SPEAKER_03: And and so then, you know, as new technologies develop, and that's important for so many things, is that you don't learn new things till a new technology is created.
• 31:52
  SPEAKER_03: Then then you have the people who do it with the technology and they say, Ah, we don't see them again.
• 31:57
  SPEAKER_03: And then another group who says, Ah, but you weren't looking for the right signature, and now we see them.
• 32:02
  SPEAKER_03: And they may have used different controls like children's brains, where there's a lot of stem cells to say, here's what the signature is, for example.
• 32:10
  SPEAKER_03: And and so, you know, different controls, different technologies.
• 32:13
  SPEAKER_03: I mean, it gets lost in the weeds for you know, for most people.
• 32:16
  SPEAKER_03: For us, everyone fights about these tiny, tiny details all the time.
• 32:20
  SPEAKER_03: I think there has been more, more things that have been done than than less that suggest that there are still stem cells there.
• 32:28
  SPEAKER_03: Um, so somewhat of the new argument is well, okay, even if they do exist, yeah, they don't do anything.
• 32:35
  SPEAKER_03: They well, you know, they're not going to be important for anything.
• 32:37
  SPEAKER_03: So now the argument's shifting a little bit.
• 32:39
  SPEAKER_03: But I can tell you recently.
• 32:41
  SPEAKER_05: I don't like that argument.
• 32:42
  SPEAKER_03: Well, there's a lot of arguing just generally, as you can see.
• 32:46
  SPEAKER_05: Yeah.
• 32:46
  SPEAKER_03: Um, but you know, we my lab in the past few years, we tried to kind of move into a few different experiments that made me feel like I was getting a better grasp on it, that I felt like could contribute to this argument.
• 32:58
  SPEAKER_03: And one is by taking tissue from patients who are getting epilepsy resections.
• 33:03
  SPEAKER_03: Um, so sometimes if they're not responsive to drugs and they can't they continue to have seizures, they will actually remove a portion of the hippocampus, the part that we are interested in, um, to because the seizure focus is there, and that actually can reduce seizures and they can have a much better life.
• 33:23
  SPEAKER_03: So we can actually, through um, you know, we have an IRB in place, so no one panic, we get them to consent.
• 33:29
  SPEAKER_03: Uh, we can actually take that tissue, which would be tested only in pathology and be thrown away.
• 33:34
  SPEAKER_03: Uh, and we can dissociate it, break it apart into the cells, and then we can look for the presence of stem cells.
• 33:41
  SPEAKER_03: And they do a very specific thing in a dish if you give them the right, you know, food.
• 33:45
  SPEAKER_03: Yeah, and that is that they will divide, they will start to replicate themselves, but they like to just stick to themselves.
• 33:51
  SPEAKER_03: So they'll just make these little balls that we call neurospheres.
• 33:54
  SPEAKER_03: It's just they divide and they stick and they divide and they stick, and it just gets bigger and bigger.
• 33:58
  SPEAKER_05: They're called neurospheres.
• 33:59
  SPEAKER_05: Neurospheres, yeah.
• 34:00
  SPEAKER_03: Yeah, it's a good name.
• 34:01
  SPEAKER_03: Yeah.
• 34:02
  SPEAKER_03: Um, it it sounds like it should be like a disco or something.
• 34:05
  SPEAKER_03: I I don't know.
• 34:06
  SPEAKER_03: I'm very nerdy.
• 34:07
  SPEAKER_03: So that would be a nerdy disco.
• 34:10
  SPEAKER_03: Yeah.
• 34:10
  SPEAKER_03: So in the end, you know, we've been able to see them.
• 34:13
  SPEAKER_03: We've been able to see that they divide.
• 34:15
  SPEAKER_03: We've been able to, you know, turn them into neurons in a dish.
• 34:19
  SPEAKER_03: We've been able to do other studies with them that look they look comparative to rodents' cells.
• 34:24
  SPEAKER_03: So for me, I'm like, I how can you ask the question if there are stem cells in the brain when I can take them out of a person's brain and I can grow them in a dish?
• 34:31
  SPEAKER_03: So I don't think that can be the question anymore.
• 34:34
  SPEAKER_03: And yet there's still controversy.
• 34:36
  SPEAKER_03: Yeah.
• 34:37
  SPEAKER_05: Okay, here's two scenarios.
• 34:39
  unknown: Okay.
• 34:41
  SPEAKER_05: First scenario, neurogenesis is possible in adults.
• 34:46
  SPEAKER_04: Okay.
• 34:47
  SPEAKER_05: What are the proposed mechanisms by which we can actually elicit neurogenesis?
• 34:52
  SPEAKER_03: Okay, so I'm gonna have to go back to rodent again.
• 34:55
  SPEAKER_03: But obviously, we have things that can increase neurogenesis.
• 34:57
  SPEAKER_03: We've learned a lot about it.
• 34:59
  SPEAKER_03: One is running, um, maybe other exercises, but if you put them in, you know, water to have them swim, this is stressful.
• 35:06
  SPEAKER_03: So that's you know, not quite the same.
• 35:08
  SPEAKER_03: But we can at least say if you put a running wheel, they voluntarily run in it, that you can boost neurogenesis this way, for example.
• 35:15
  SPEAKER_03: Um, the other thing is what we call enhanced environment or enriched environment.
• 35:21
  SPEAKER_03: And this is you know, in an area with in uh novel items, social interaction that is not aggression, um, lots of, you know, interesting things that, you know, that aren't usually in there, not just like a blank cage with a water bottle in it, but you know, tubes and things to crawl on and you know, things to rip into shred and you know, the wheels, et cetera.
• 35:43
  SPEAKER_03: Right, exactly.
• 35:44
  SPEAKER_03: So novel, novel, you know, learning just generally.
• 35:47
  SPEAKER_03: And and those are the two really strongest um drivers of proliferation and survival.
• 35:53
  SPEAKER_03: Um, and then of course, you may have heard this thing called, you know, use it or lose it kind of thing.
• 35:58
  SPEAKER_03: Once you've made them, if you do not have some kind of uh recruitment of those neurons with new learning or some something like this, right?
• 36:08
  SPEAKER_03: Um, they'll die.
• 36:10
  SPEAKER_03: So you have to have some kind of new learning as well.
• 36:13
  SPEAKER_03: So if you were gonna take that to a human condition, exercise, read books, go outside.
• 36:18
  SPEAKER_03: Yeah, and maybe have some and have some friends, maybe do that.
• 36:22
  SPEAKER_03: What a surprise.
• 36:22
  SPEAKER_03: Yeah, yeah.
• 36:23
  SPEAKER_03: And actually, there's two the two strongest negative regulators in rodents is stress, which is bad for me, and um, and the other is age, which is probably also not gonna be very good for me coming up either.
• 36:36
  SPEAKER_03: Um, so just generally, I think if you apply any of those concepts to a human, yeah, this is gonna help more than just neurogenesis as well.
• 36:47
  SPEAKER_03: So I I think it's kind of, you know, there's no harm in assuming that it does.
• 36:54
  SPEAKER_05: We should try and weave in time for those things anyway.
• 36:56
  SPEAKER_03: Exactly.
• 36:57
  SPEAKER_03: Shoulds, though, you know.
• 36:58
  SPEAKER_05: Yeah, well, and that's the truth.
• 37:00
  SPEAKER_05: Um, any information on nutrient intake and potential impact?
• 37:05
  SPEAKER_03: Yes, so this is actually still, you know, ongoing.
• 37:08
  SPEAKER_03: Um, some some recent studies would suggest that some of the some of the things that are you know most uh looked at out there, intermittent fasting, things like that, don't have the same effects on adult neurogenesis that one might expect.
• 37:22
  SPEAKER_03: And yet uh I have a good friend who studies you know lipid uptake, for example, and this can actually affect how the stem cells behave quite a lot.
• 37:31
  SPEAKER_03: So I would say we don't know well enough.
• 37:33
  SPEAKER_03: Um, and so it's a bit of a mixed bag at the moment.
• 37:36
  SPEAKER_03: It's also very hard in the context of a very controlled diet that you have in these rodent conditions, right?
• 37:43
  SPEAKER_03: Uh as well.
• 37:44
  SPEAKER_03: But uh I I would say I I wouldn't go one way or the other on these yet that the data aren't as strong enough.
• 37:51
  SPEAKER_05: I would imagine very poor nutrient intake would probably lead the in the other direction, or like high alcohol intake or like toxin or yeah.
• 38:01
  SPEAKER_03: I mean there's other parts of the brain that are also gonna be very badly affected by this for sure.
• 38:05
  SPEAKER_05: So Okay, scenario two.
• 38:07
  SPEAKER_05: Okay Neurogenesis in adults is not possible.
• 38:12
  SPEAKER_05: Do we start with a finite amount of these stem cells?
• 38:16
  SPEAKER_05: And if yes, how do we protect them as we age?
• 38:22
  SPEAKER_03: So I don't usually think on this side of the coin as the eternal optimist as well.
• 38:27
  SPEAKER_03: So let me think about this a moment.
• 38:29
  SPEAKER_03: So how do you protect them?
• 38:30
  SPEAKER_03: So there is gonna still be some turnover, just generally, yeah.
• 38:34
  SPEAKER_03: But um if you think about learning, you know, this is like uh aspects of repetition, right?
• 38:42
  SPEAKER_03: You that you learn something and the next day you revisit it again, the next day you revisit it again, the next day you revisit.
• 38:49
  SPEAKER_03: This is how our learning works in the end.
• 38:52
  SPEAKER_03: Just I try to tell this to my kids all the time when they're like, you can't just study, you know, one night and hope it's gonna stick in there.
• 38:58
  SPEAKER_03: Um I also don't think I listened to that when I was in here either.
• 39:02
  SPEAKER_03: Um, so I think that aspect is protective just generally from the neurons that you have as well in these regions.
• 39:09
  SPEAKER_03: But I think there's a lot that's being seen about changes in the vasculature in the brain.
• 39:14
  SPEAKER_03: The hippocampus is a highly vascular region.
• 39:17
  SPEAKER_03: So I think anything that we can do to improve blood flow, oxygenation, and in vasculascular integrity is going to improve all of these things just generally.
• 39:28
  SPEAKER_05: Probably why exercise is so beneficial.
• 39:31
  SPEAKER_03: And also, I mean, these stem cells are in a vascular niche, is what we call the region that they live, right?
• 39:37
  SPEAKER_03: So they are really interacting with the vasculature.
• 39:40
  SPEAKER_03: So we have some um, we do some experiments where we're able to actually visualize the stem cells in the brain in an animal um through a window, a skull window.
• 39:49
  SPEAKER_03: And you can look at these same stem cells and watch them as you do exercise or do different things and see, and you can see that many of them are interacting with the blood vessels just generally.
• 39:59
  SPEAKER_03: And so, of course, they're going to have, if you change something that's flowing through the blood, they have the potential to be able to react to that as well.
• 40:07
  SPEAKER_05: A vascular niche.
• 40:09
  SPEAKER_03: Yeah.
• 40:09
  SPEAKER_03: So so if you think about, you know, where things are located, where neurons are, where different cell types are, these are all kind of very tightly kind of opposed up near where the vessels are or having an interaction with them.
• 40:25
  SPEAKER_03: And it's similar to another cell type that they're similar to, um, which are called astrocytes, which actually are important in lots of different things, but also they have their feet basically touching it.
• 40:36
  SPEAKER_03: Um, their N feet are part of what we call the blood brain barrier as well.
• 40:40
  SPEAKER_03: So I think everything that has these connections to the vasculature would be improved dramatically by anything that's going to improve your vascular integrity.
• 40:48
  SPEAKER_05: Improve blood very nutrient-rich, yeah.
• 40:51
  SPEAKER_05: Okay.
• 40:53
  SPEAKER_05: Can you the there's a word that you use often?
• 40:58
  SPEAKER_05: Quiescence.
• 40:59
  SPEAKER_03: Quiescence, yeah.
• 41:00
  SPEAKER_05: I love that word.
• 41:01
  SPEAKER_03: Oh, okay.
• 41:04
  SPEAKER_05: Can you uh explain to the listeners what that means in the context of these dormant stem cells?
• 41:12
  SPEAKER_03: Yeah, so I you know, it's funny there's another word that people often associate quiescence with that is not the same.
• 41:19
  SPEAKER_05: You say quiescence or quiescence.
• 41:21
  SPEAKER_03: Uh uh Well, I'm very American, so I say quiescence, but I I you can have quiescence if you'd like.
• 41:27
  SPEAKER_03: That can be your split between the two.
• 41:30
  SPEAKER_03: But there's another word that is very similar that people sometimes think mean the same thing, which is senescence.
• 41:35
  SPEAKER_03: Yes, and that's different.
• 41:37
  SPEAKER_03: So maybe I can define both to kind of explain that difference.
• 41:40
  SPEAKER_05: I would love that.
• 41:41
  SPEAKER_03: Okay, so quiescence is really the state of being out of the cell cycle.
• 41:47
  SPEAKER_03: So they are they are not actively dividing, but there's the ability to be able to re-enter.
• 41:53
  SPEAKER_03: So stem cells have a reversible quiescence.
• 41:56
  SPEAKER_03: They're on the bench.
• 41:58
  SPEAKER_03: They're on the bench.
• 41:58
  SPEAKER_03: Yeah, they're kind of I like I mean, I really visualize them because of how they have, you know, they have so many receptors, they're trying to really listen.
• 42:05
  SPEAKER_03: They're just like, should I do something yet?
• 42:07
  SPEAKER_03: I'm waiting to hear, should I do something?
• 42:09
  SPEAKER_03: And if they get a signal that says I should do something, everything kind of gets pulled inside and they start trying to make enough to duplicate themselves.
• 42:18
  SPEAKER_03: And that can be really almost all that they think about.
• 42:21
  SPEAKER_03: And so they are not very, they're not listening at that point because everything is about, all right, I got the signal.
• 42:27
  SPEAKER_03: Now I need to just run the play and not dividing.
• 42:29
  SPEAKER_03: I'm in the cell cycle.
• 42:30
  SPEAKER_01: Yeah.
• 42:31
  SPEAKER_03: So you exit quiescence in that case.
• 42:34
  SPEAKER_03: So stem cells in the uh in the adult brain, also in other parts of the body, can be in this reversible quiescent state, still able to re-enter and divide.
• 42:45
  SPEAKER_03: Senescence is also out of the cell cycle.
• 42:48
  SPEAKER_03: They are also not dividing, but this is actually pathological.
• 42:52
  SPEAKER_03: Um, they can't re-enter and they actually turn, there's a saying that they, you know, that they turn into like a zombie cell.
• 43:00
  SPEAKER_03: Yeah, exactly.
• 43:01
  SPEAKER_03: Because they aren't making what they should be doing, they're doing a different job, and they they actually are releasing a lot of things that are toxic to everything around them.
• 43:10
  SPEAKER_03: That is very different.
• 43:11
  SPEAKER_03: Quiescent cells are not doing that.
• 43:13
  SPEAKER_03: That's uh so that's kind of where the difference is.
• 43:16
  SPEAKER_03: But both of them are not dividing, they're both outside of this cell cycle stage.
• 43:21
  SPEAKER_03: And can neuronal stem cells be both so this is an area that people have been looking at.
• 43:29
  SPEAKER_03: Um, I would say this is also a little controversial.
• 43:33
  SPEAKER_03: Uh, there have been some data that would suggest not those cells themselves, but actually another stage towards becoming a neuron later have shown markers of senescence.
• 43:47
  SPEAKER_03: Uh it's it's it's complicated because some of the markers are also present in both conditions and things like this.
• 43:54
  SPEAKER_03: And so I would say I wouldn't, I wouldn't, this is an area that's still gray.
• 44:00
  SPEAKER_03: That's not worked out.
• 44:01
  SPEAKER_05: What does with both of those terms, what do they like practically mean to people?
• 44:06
  SPEAKER_05: You know, when we're talking about protecting our brain against decline.
• 44:12
  SPEAKER_03: So I mean, probably it shouldn't mean anything to the people walking, you know, every day because you don't think about those kind of those details down to single cell levels.
• 44:21
  SPEAKER_03: But what it could mean is, you know, there are a lot of treatments, a lot of clinical trials now addressing senescent cells because they increase inflammation so much in the body, but specifically also in the brain, neuroinflammation as well.
• 44:36
  SPEAKER_03: And this other cell type I mentioned, astrocytes, for example, they can also become senescent.
• 44:42
  SPEAKER_03: And so if you have this increased inflammation, there are some treatments or conditions where people have been trying to target those cells to kill them when they should have died before.
• 44:52
  SPEAKER_03: The idea was that they should have died and they didn't, and now they're in this stage.
• 44:56
  SPEAKER_03: So there are a lot of things targeting senescence.
• 44:59
  SPEAKER_03: Um quiescence is really something that's more of a of a stage that's more associated with, you know, the study of how a stem cell behaves and how does it exit.
• 45:11
  SPEAKER_03: And so I think the general population wouldn't think as much about this stage.
• 45:15
  SPEAKER_03: But senescence is actually something that people as tar people are targeting.
• 45:18
  SPEAKER_05: But but with quiescence, you know, we took you the analogy used was they're like little radars looking for signal.
• 45:25
  SPEAKER_05: How do we get them to acknowledge the signal?
• 45:29
  SPEAKER_03: It might not even be that they have to acknowledge the signal, and maybe that the signals have changed.
• 45:34
  SPEAKER_03: Um, and that's and that actually can happen because, you know, a lot of this inflammation, for example, that might be something that tells them not to divide.
• 45:43
  SPEAKER_04: Right.
• 45:43
  SPEAKER_03: Um, there have been some really interesting studies that have come out of of Germany that would suggest that the the niche, the things that they're exposed to in their in their home, has ch changes a lot with aging, and that these are kind of anti, you know, divided proliferation or division.
• 46:00
  SPEAKER_03: So that they're being stuck in this stage this way.
• 46:03
  SPEAKER_03: So that the niche itself is driving a lot of that.
• 46:05
  SPEAKER_03: How do we modify that yet?
• 46:07
  SPEAKER_03: I don't think we have an idea.
• 46:09
  SPEAKER_05: A bit too early.
• 46:09
  SPEAKER_03: But you have to know first that there's a problem before you can figure out how to address it.
• 46:13
  SPEAKER_03: So um, I think it may not even be that they're not being responsive, it may just be that they're getting signals that are quite different.
• 46:21
  SPEAKER_05: Huh.
• 46:22
  SPEAKER_03: Yeah.
• 46:22
  SPEAKER_05: It's really challenging for just generally just to understand.
• 46:27
  SPEAKER_05: Um, it's just challenging in general, I think, for people listening.
• 46:32
  SPEAKER_05: Because many people listening will have heard of the term senescence and zombie cells.
• 46:37
  SPEAKER_03: Yes.
• 46:38
  SPEAKER_05: But not really know what to do with that information or or those terms.
• 46:42
  SPEAKER_05: But yet we see a lot of bold claims and products and tools that are maybe leveraging that fact that we don't understand.
• 46:52
  SPEAKER_03: I mean, hype is a real thing.
• 46:53
  SPEAKER_05: Yeah.
• 46:54
  SPEAKER_03: Um, there are always going to be people who will take information um and utilize the lack of knowledge in the general population and take advantage of that and in different ways.
• 47:05
  SPEAKER_03: That will always happen.
• 47:06
  SPEAKER_03: I mean, the way to guard against that is looking for clinical trials from people who are the scientists who I identify those things, right?
• 47:14
  SPEAKER_03: Or looking for FDA approved uh versions of treatments, for example.
• 47:19
  SPEAKER_03: Yeah.
• 47:19
  SPEAKER_03: Um, and that goes with like the stem cell transplantation and the stem cell topic as well.
• 47:25
  SPEAKER_03: Um, I think you just cannot get away from that.
• 47:30
  SPEAKER_03: That the humanity is is always going to have all types.
• 47:35
  SPEAKER_00: Yeah.
• 47:36
  SPEAKER_03: Um, but you can, if you're confused and you are wondering, should I do this, should I not do this, then I would start by going to experts and trying to figure this out.
• 47:45
  SPEAKER_03: In the same way that if I wanted to build the house, I wouldn't ask my, you know, the grocery store guy to build my house.
• 47:50
  SPEAKER_03: I would want a really good architect to build my house.
• 47:53
  SPEAKER_03: If I were thinking about something to address senescence cells, or should I use it or is it important?
• 47:57
  SPEAKER_03: I would go to an expert.
• 47:59
  SPEAKER_03: Yeah.
• 47:59
  SPEAKER_03: I would go to a clinical trial.
• 48:00
  SPEAKER_03: I would go to, you know, a website of a scientist who's worked on that.
• 48:04
  SPEAKER_03: And these days, those things are much easier to do than they used to be.
• 48:08
  SPEAKER_05: Be curiously skeptical.
• 48:10
  SPEAKER_03: I am always skeptical.
• 48:11
  SPEAKER_03: Yes.
• 48:12
  SPEAKER_03: Optimistic, but skeptical.
• 48:14
  SPEAKER_03: Yeah.
• 48:14
  SPEAKER_05: I feel like I might be a bit too skeptical at times.
• 48:16
  SPEAKER_03: I that's I feel like that's better.
• 48:18
  SPEAKER_03: That's a better side of things to be on.
• 48:21
  SPEAKER_03: I mean, we have to be critical.
• 48:22
  SPEAKER_03: Uh, we're trained in in our training.
• 48:25
  SPEAKER_03: This is like actually something you're learning, is how do you be critical?
• 48:28
  SPEAKER_03: When you see someone publish a paper, um, and you say, okay, they made this claim.
• 48:34
  SPEAKER_03: Did they do the experiments to prove this claim?
• 48:37
  SPEAKER_03: Let's go into the methods, let's see how they did it.
• 48:39
  SPEAKER_03: Ah, they they really, you know, this is a weak claim.
• 48:42
  SPEAKER_03: It's not, we learn how to be critical all the time, so we can be critical of our own work and we can we can then publish things that are you know valid.
• 48:50
  SPEAKER_05: Yeah.
• 48:51
  SPEAKER_03: But that's actually a skill set that's well.
• 48:54
  SPEAKER_05: Here's the problem, though, Darcy.
• 48:56
  SPEAKER_05: That's a skill set I think not many people have, right?
• 48:58
  SPEAKER_05: Most, in fact, most of us don't have, yeah, because we're not scientists.
• 49:04
  SPEAKER_05: And so it is kind of challenging.
• 49:05
  SPEAKER_05: We we spoke about this off camera.
• 49:07
  SPEAKER_05: Not all research is created equal.
• 49:09
  SPEAKER_05: So you can you get published peer-reviewed journals, yeah, and they're not as good as one another.
• 49:14
  SPEAKER_05: Yes, they're not.
• 49:15
  SPEAKER_05: And so, like, we're having to, as the normal everyday person, figure out well, I know that it should be grounded in evidence, but how strong is the evidence?
• 49:24
  SPEAKER_03: It's true.
• 49:25
  SPEAKER_03: It would be really a very confusing time right now.
• 49:28
  SPEAKER_03: And I know even for my own family, none of whom are scientists, um, I'm like the the person they come to.
• 49:35
  SPEAKER_03: So, like, well, what do you think about this?
• 49:37
  SPEAKER_03: I mean, even you know, back to the days of you know, COVID vaccines and things like this, you know, I people come to me, I don't know who to believe.
• 49:45
  SPEAKER_03: Talk to me about what you know, what you have read.
• 49:47
  SPEAKER_03: Because in the end, there's somewhat also an element of consensus, right?
• 49:51
  SPEAKER_03: If you have this one outstanding claim and it's one paper and you have, you know, 20 that have done it in different ways that it say no, then you know, there is an element of that as well.
• 50:05
  SPEAKER_00: Yeah.
• 50:05
  SPEAKER_03: Um, we also, you know, for us, we have kind of impact uh levels for different journals as well.
• 50:13
  SPEAKER_03: So that often, you know, there's rigorous peer review.
• 50:17
  SPEAKER_03: Other scientists like myself will look at a paper and rip it apart and then say, you need to do this experiment, you need to do this, you can't say this.
• 50:25
  SPEAKER_03: And then the people go back, they change their study, they add, they don't, and then finally it can get you know accepted into a journal.
• 50:33
  SPEAKER_03: So it goes through that.
• 50:34
  SPEAKER_03: And those levels of peer review and the stringency of those might be different with different quality of journals as well.
• 50:42
  SPEAKER_03: But you're right, it is a really hard, confusing thing to think about.
• 50:46
  SPEAKER_05: Um tough out there.
• 50:47
  SPEAKER_03: It is, but I would also say I think about this in other ways because you know, I investments like for me, I feel like how do I figure out what to invest in?
• 50:56
  SPEAKER_03: I have no idea.
• 50:57
  SPEAKER_03: I and so then I go to an expert, right?
• 51:00
  SPEAKER_03: So and so I think that's ultimately what anyone has to do.
• 51:03
  SPEAKER_03: Uh it no one can become an expert in everything, um, unfortunately.
• 51:08
  SPEAKER_05: Very true.
• 51:08
  SPEAKER_05: Yeah.
• 51:09
  SPEAKER_05: That's why this counts, that's why we brought together the council in the first place.
• 51:12
  SPEAKER_05: I think that that longevity is often treated as a captured term now, is a buzzword.
• 51:17
  SPEAKER_05: It is where a longevity expert will give advice with almost certainty across these different verticals, and that's more confusing than ever.
• 51:26
  SPEAKER_03: It's somewhat easier to do in the longevity uh you know situation because people will live for you know 20, 30 more years, right?
• 51:35
  SPEAKER_03: So I might they might be able to say this right now, but there's not an immediate response, right?
• 51:40
  SPEAKER_03: As opposed to like a cancer treatment or something like that, where it's very acute, you get the results, you have information right away.
• 51:46
  SPEAKER_03: But you can make any claim now and you wouldn't have to, you know, have to face that claim if it was true or not.
• 51:52
  SPEAKER_05: I guess that's why aging is so difficult to study, right?
• 51:54
  SPEAKER_03: Oh yeah.
• 51:55
  SPEAKER_03: No one do you want to do a clinical trial on aging humans?
• 51:59
  SPEAKER_03: That sounds no, I don't think I have that many years left.
• 52:02
  SPEAKER_05: I think though, when we talk about longevity, there there's two people have two different ideas of what that means.
• 52:08
  SPEAKER_05: Like there's the you know, we can lean into science and biotech, and we'll be able to extend the lifespan by decades of functional years.
• 52:17
  SPEAKER_05: And I and I'm actually kind of bullish that eventually that will happen.
• 52:20
  SPEAKER_05: I don't know if it's anywhere as close as people are suggesting, but the rate at which some of the um tools, technology, research is being developed, I think that's sped up, right?
• 52:32
  SPEAKER_05: And it was already very promising.
• 52:34
  SPEAKER_05: I think it's nowhere near as close as as we're being led to believe, but I do think that those things will happen eventually.
• 52:41
  SPEAKER_05: But I think what we speak so much more optimistically about, and I think rightly so, is the ability to add decades of functional years, not necessarily to lifespan, but just to health span health span.
• 52:56
  SPEAKER_01: Right, exactly.
• 52:56
  SPEAKER_05: Right.
• 52:56
  SPEAKER_05: And I think I want to I want to take a slight optimistic turn here because I've been a little pessimistic so far.
• 53:03
  SPEAKER_05: We do know a lot of things that can help contribute to um improving or at least maintaining brain function now that, and again, this was something we touched on off camera, that we can say without having absolute certainty across the board, but has the appropriate level of risk reward, right?
• 53:21
  SPEAKER_05: I think I think most of them we can say nothing we can say with absolute certainty.
• 53:25
  SPEAKER_03: No, I'm generally a gray, a gray gal, nothing black and white, yes.
• 53:28
  SPEAKER_05: Yeah, but I think you know it's safe to say, unsurprisingly, that exercise, sleep, um, stress management, human connection, nutrient density are all going to contribute to your likelihood of living a longer, healthier life.
• 53:45
  SPEAKER_03: I I definitely agree.
• 53:47
  SPEAKER_03: Um, I think reality is such, though, that our lives these days just make it very complicated to be on top of all of those things all the time.
• 53:56
  SPEAKER_03: Um so in the end, we may be able to do a few of those things now and again, different stages of our life.
• 54:03
  SPEAKER_03: We may be able to invest more or less in those things.
• 54:06
  SPEAKER_03: Um, but I think just generally, I find this as a challenge just for myself, you know, regularly.
• 54:12
  SPEAKER_03: How I know I know what I should be doing.
• 54:14
  SPEAKER_03: Yes, yeah, yeah.
• 54:15
  SPEAKER_03: But I have to make choices every day and you know what I I think is important.
• 54:20
  SPEAKER_03: And, you know, I I have work, I have the the people I mentor, I have my family, I have my children, uh, you know, and and how do you work, how do you work self-care into that?
• 54:31
  SPEAKER_03: That's a challenge.
• 54:32
  SPEAKER_03: So right now I think our society needs to modify a little bit to allow there to be room for self-care, to allow for those things to happen.
• 54:39
  SPEAKER_03: And there's another, oh there's a lot of other pieces in there that, you know, I don't think we have flushed out as well either, besides the risk for disease, which, you know, that's gonna derail your longevity mission as well in many cases.
• 54:51
  SPEAKER_03: Yeah, you're and also just, you know, sex differences, menopause, for example.
• 54:56
  SPEAKER_03: I mean, yes, you brain fog, words gone.
• 54:59
  SPEAKER_03: What do you do in those in those situations?
• 55:01
  SPEAKER_03: You could still be doing all the right things, but you've just lost a major hormone, for example, yeah, out of your body.
• 55:06
  SPEAKER_03: So I think it's very complicated and human variability between each person is gonna be challenging.
• 55:13
  SPEAKER_03: And today we have, you know, centenarians, we have supercentenarians, we have, I've mentioned them, you know, our lineage of people who lived in their 90s in your family or things, you know, my great-grandma, for example.
• 55:26
  SPEAKER_03: We will still have those people, they will still exist.
• 55:29
  SPEAKER_03: But I think right now, society, I mean, I'm the pessimistic one now.
• 55:33
  SPEAKER_03: What have you done to me?
• 55:34
  SPEAKER_03: Uh I think society doesn't make it doesn't make room for that right now.
• 55:39
  SPEAKER_03: Self-care is, you know, we talk a lot about it and we're all looking for it.
• 55:43
  SPEAKER_03: But every day to be able to make a choice that involves aspects of self-care to do the things we know we should be doing, I think it's really hard.
• 55:50
  SPEAKER_05: Yeah.
• 55:51
  SPEAKER_05: And I think we're made to feel a little guilty when we don't.
• 55:54
  SPEAKER_05: Or we're made to feel like we're fake.
• 55:56
  SPEAKER_03: All around.
• 55:57
  SPEAKER_03: There's guilt if I don't spend time with my family.
• 55:59
  SPEAKER_03: There's guilt if I don't do self-care, if I don't work more than you know, 80 hours a week.
• 56:03
  SPEAKER_03: There's guilt everywhere.
• 56:04
  SPEAKER_03: So yeah, like yeah, that's something a mission that I think we all have to get uh to work on, which is trying to find a way out of the guilt as well.
• 56:12
  SPEAKER_05: Yeah.
• 56:13
  SPEAKER_05: It's nuanced.
• 56:14
  SPEAKER_05: There, there's there's so much that's what we're trying to help find the answers to, right?
• 56:19
  SPEAKER_05: And that's the kind of the purpose of doing this in the first place.
• 56:22
  SPEAKER_05: You know, it's difficult, even when you know all of the things that you're supposed to be doing, to actually carve out time to do them.
• 56:29
  SPEAKER_05: I think that's safe to say.
• 56:31
  SPEAKER_05: And then you have to do that forever.
• 56:33
  SPEAKER_03: I know, right?
• 56:34
  SPEAKER_05: Like, no, it's a big ask, right?
• 56:36
  SPEAKER_03: It's true.
• 56:37
  SPEAKER_03: I I think you know, to what end are we doing it?
• 56:40
  SPEAKER_03: I think is the I mean, you feel better.
• 56:42
  SPEAKER_03: I mean, I feel better.
• 56:42
  SPEAKER_03: Like right now, you know, my my mobility's been a little challenged.
• 56:46
  SPEAKER_03: I've been trying to work yoga in.
• 56:48
  SPEAKER_03: I feel much better after I do a few sun salutations, right?
• 56:51
  SPEAKER_03: Yeah, yeah.
• 56:52
  SPEAKER_03: I know that.
• 56:52
  SPEAKER_03: And then I think, uh, but that's gonna take me how much time I need to be able to do this, this, and this, and this before this meeting, do I have time to work it in?
• 57:01
  SPEAKER_03: I don't.
• 57:01
  SPEAKER_03: And no one's gonna be like, oh, she did yoga today.
• 57:04
  SPEAKER_03: They're gonna be like, did she, you know, present well in this thing I have to do?
• 57:08
  SPEAKER_03: So, you know, if there's a way in businesses or in different aspects of the world we live in where people say, okay, you're gonna work an eight-hour day or whatever, 20 hours day, whatever, uh, depending on your field that you're in.
• 57:24
  SPEAKER_03: But, you know, here's a gym on site for one hour, this is when you'll go to the gym, right?
• 57:31
  SPEAKER_03: If someone made that that was an expectation that they're as well, I don't know.
• 57:36
  SPEAKER_03: I think that would change the way we think about it.
• 57:38
  SPEAKER_05: You mean like ways to sort of carve it in that make it just easier to adhere to with consistency?
• 57:42
  SPEAKER_03: Exactly.
• 57:43
  SPEAKER_03: Because right now, if I don't do any self-care, no one cares, right?
• 57:46
  SPEAKER_03: There's no one cares if I've invested in myself or not.
• 57:49
  SPEAKER_03: And if it felt like there were other people who were also invested in me taking care of myself.
• 57:54
  SPEAKER_05: Well, I think there are.
• 57:55
  SPEAKER_05: I think, I think playing devil's advocate.
• 57:58
  SPEAKER_05: Please.
• 57:58
  SPEAKER_05: I think when we carve out time deliberately to focus on improving the way that we feel through the means that we know work, everyone else gets a better version of you.
• 58:10
  SPEAKER_03: I agree with that.
• 58:12
  SPEAKER_03: We are on the same page with that, but I still think making the time is hard.
• 58:18
  SPEAKER_03: I mean, I my husband and my children would definitely agree that when when mama is happy, everyone's happy.
• 58:25
  SPEAKER_03: Right, yeah.
• 58:26
  SPEAKER_03: So I think that's true.
• 58:28
  SPEAKER_05: I do think as well, it's a bit of a fallacy that that we don't, you know, just I think there's a difference between being at work and doing good work, right?
• 58:39
  SPEAKER_05: And I think my other argument would be when we are feeling good and performing well and we have energy and and and motivation and concentration, we'd yield a higher return on the work we do anyway.
• 58:52
  SPEAKER_05: And so the argument that you'd be at work less, I think is less convincing.
• 58:58
  SPEAKER_03: This is not my expertise, this is your expertise, I would say.
• 59:02
  SPEAKER_03: So I would I would uh say that.
• 59:04
  SPEAKER_05: I I think I think there's a middle ground to be had, you know, the way I I often recommend at least our members doing this, certainly when you're going through periods of life when you're very time restricted and everyone does, um, that you create some non-negotiable time to focus on you selfishly, but that could be 15-20 minutes a day.
• 59:26
  SPEAKER_05: And I don't buy into the idea that we can't find 15 to 20 minutes given the return that it gives us.
• 59:33
  SPEAKER_05: The the challenge is being motivated to do the thing, right?
• 59:37
  SPEAKER_05: And like that is that can be difficult sometimes if you wake up and you're feeling exhausted, or you know, you haven't had enough sleep, or the you know, the kids are jumping on you first thing in the morning, or you're feeling stressed about work, that's when it becomes you have to rely on discipline rather than motivation, and that is very difficult.
• 59:55
  SPEAKER_05: Yes, but doable.
• 59:56
  SPEAKER_03: I'm gonna use these words and try to apply them to my life.
• 59:59
  SPEAKER_03: We'll see.
• 1:00:00
  SPEAKER_03: I'll see if I can use it.
• 1:00:02
  SPEAKER_05: A really good way of doing it, I think, is removing as many barriers as you can to actually starting.
• 1:00:09
  SPEAKER_05: And so when I go through these periods of like immense stress or like being like super time restricted, or have a big project on, I'll carve in five minutes a day to do the thing.
• 1:00:20
  SPEAKER_05: Often it is just starting the exercise or just starting the preparation of the food or whatever it is you're trying to aim for, is it's the idea of actually starting five minutes in, you're like, Oh, I could probably get away with doing another 10 minutes or another 15 minutes, and then it it it compounds over time very quickly.
• 1:00:38
  SPEAKER_05: Yes, doesn't always work, but uh I think psychologically as well, ticking that box is a win.
• 1:00:46
  SPEAKER_03: I I think it is a win when I do it, it feels great.
• 1:00:49
  SPEAKER_03: I agree, I agree.
• 1:00:51
  SPEAKER_05: Not easy though, Darcy.
• 1:00:53
  SPEAKER_05: Um, can we can I ask you something?
• 1:00:55
  SPEAKER_05: Is there something in your field that you see?
• 1:00:58
  SPEAKER_05: I know you don't use social media, but when I don't just the media in general or or or dinner party conversations or uh, you know, when you're at work that you just wish people would stop saying about stem cells or brain health or science in general?
• 1:01:13
  SPEAKER_03: Yeah, I you know, I hear, and even though I'm not actively on social media, of course, things come by.
• 1:01:19
  SPEAKER_03: Oh, you know, did you see this thing this person said?
• 1:01:22
  SPEAKER_03: You know, things like that.
• 1:01:24
  SPEAKER_03: Um, I think people overpromise and overclaim a lot.
• 1:01:29
  SPEAKER_03: Um and this this is I think something that really drives me crazy as a scientist mostly, because we try very hard not to overclaim, not to overstate.
• 1:01:42
  SPEAKER_03: And when scientists do it, it's even more upsetting as well, because they're coming from a voice of expertise as well and trust, right?
• 1:01:51
  SPEAKER_03: And and you know, we have we we have discussions sometimes with graduate students about you know this science and and society, what are your responsibilities as a scientist to to the society?
• 1:02:02
  SPEAKER_03: And I feel like you know, when people make these types of claims, um it feels a lot like snake oil salesmen as opposed to rigorous scientific um integrity.
• 1:02:16
  SPEAKER_03: Um and so I think this is the one of the things that's driving me crazy these days because voices that are loud and that are that are you know are respected sometimes are saying things that I think are not appropriate.
• 1:02:30
  SPEAKER_05: Yeah, and in a way that is kind of compelling, right?
• 1:02:33
  SPEAKER_05: Because sometimes we want it to be true as well.
• 1:02:36
  SPEAKER_03: Yes, yes, exactly.
• 1:02:38
  SPEAKER_05: Have you got an example of that?
• 1:02:39
  SPEAKER_03: I don't know that I want to do that.
• 1:02:42
  SPEAKER_05: I thought that might be your answer.
• 1:02:44
  SPEAKER_03: I also have mixed emotions about everyone telling me everything that they do every day for trying to, you know, here's what I'm taking, and you know, the biohacking business as well, because everybody is very different from each other.
• 1:02:57
  SPEAKER_03: And certainly, you know, what you're doing for your body may be very different from someone else's body and could have very bad results in someone else.
• 1:03:07
  SPEAKER_03: And sometimes when it's given in a way that is suggestive or like you should do this too, I just feel like it can be more dangerous than others.
• 1:03:15
  SPEAKER_03: I know a lot of people who like it because they want to know, they want to be like up on you know what's what are people doing these days.
• 1:03:21
  SPEAKER_03: Um, but I I think the idea is that they have done all this research before they've done it, and that's why they're doing these things.
• 1:03:28
  SPEAKER_03: I don't think that's actually the case.
• 1:03:30
  SPEAKER_03: I think um this is something that also worries me these days.
• 1:03:33
  SPEAKER_05: If you were to to look back over your career, hey, let's can we tell people about what you did before science?
• 1:03:40
  SPEAKER_05: I guess.
• 1:03:41
  SPEAKER_05: Yeah.
• 1:03:41
  SPEAKER_05: You're a professional opera singer.
• 1:03:43
  SPEAKER_03: Yes, I I I definitely have had a different few different paths.
• 1:03:46
  SPEAKER_05: That's a great, you gotta write a book at the end of this.
• 1:03:49
  SPEAKER_03: Uh I don't know.
• 1:03:51
  SPEAKER_05: Would you ever go back to opera?
• 1:03:53
  SPEAKER_03: Um, go going back to opera is kind of like saying, Oh, you were a track star and now you're like 50, and like, oh, can you go back and be a track star?
• 1:04:01
  SPEAKER_03: This is kind of the age where also your vocal cores are changing quite a lot, um, you know, with hormonal changes, etc.
• 1:04:07
  SPEAKER_03: Yeah.
• 1:04:08
  SPEAKER_03: But it's not just that.
• 1:04:08
  SPEAKER_03: It's obviously, you know, the practice that you were doing daily for years and years and years.
• 1:04:13
  SPEAKER_03: I don't have time for that anymore.
• 1:04:15
  SPEAKER_03: So the quality will never be quite the same.
• 1:04:17
  SPEAKER_05: But would you like do you like the idea of it?
• 1:04:19
  SPEAKER_03: I I like that.
• 1:04:20
  SPEAKER_03: I love the idea.
• 1:04:21
  SPEAKER_03: But I Do you do it at home?
• 1:04:22
  SPEAKER_03: I actually so now my with that my kids are older, you know, we do things together a lot.
• 1:04:28
  SPEAKER_03: And my daughter loves to sing and as well, so that's been kind of fun.
• 1:04:32
  SPEAKER_03: But uh what I miss the most is performing.
• 1:04:34
  SPEAKER_00: Yeah.
• 1:04:35
  SPEAKER_03: And um and I I think I get I get my you know performing kicks out of teaching.
• 1:04:41
  SPEAKER_03: And so I think that and and giving talks in different places, I think that satisfies that piece for me.
• 1:04:47
  SPEAKER_03: Yeah, yeah.
• 1:04:48
  SPEAKER_03: Um but I you know, I still I I loved doing it when I did it.
• 1:04:53
  SPEAKER_03: I still love doing it when I went back to school for science.
• 1:04:56
  SPEAKER_03: Um it's just a very difficult uh career to have you can't dip in and out.
• 1:05:04
  SPEAKER_03: Yeah, you can't dip in and out, and it's really hard to to to make it be, you know, financially viable as well.
• 1:05:11
  SPEAKER_03: Um and you know, there are as with many people, there are many things that you're good at, the things that many things that you like.
• 1:05:17
  SPEAKER_03: And sometimes there are moments in time in your life where things happen and it's a it's an opportunity to be like, I'm gonna just I'm gonna just you know try something different right now.
• 1:05:27
  SPEAKER_03: And it they don't come frequently, and most people don't want to do something like that because it's very destabilizing, yeah, especially when you are really good at something and then you try something new and you're terrible at it, and you're like, oh my gosh.
• 1:05:38
  SPEAKER_05: Which you often are, right?
• 1:05:39
  SPEAKER_03: Right, exactly.
• 1:05:40
  SPEAKER_05: So um if you go back to that first day of that switch, you know, when you switch to becoming a scientist, if you could go back to that day right now, is there anything that you would tell yourself about what to expect over the next like what one bit of advice would you have given the day one Darcy Moore scientist?
• 1:06:00
  SPEAKER_03: I think well, when I did the switch, I was really excited about it.
• 1:06:03
  SPEAKER_03: I wasn't really scared, which is weird.
• 1:06:06
  SPEAKER_03: Um, but I guess I would say, you know, make plans, but be flexible because I, you know, I had very distinct goals.
• 1:06:16
  SPEAKER_03: And sometimes it depends on did you find an important finding?
• 1:06:20
  SPEAKER_03: Did you, you know, publish in a certain journal?
• 1:06:23
  SPEAKER_03: And you can't make the next career step or the next plan until that, you know, that metric has been met.
• 1:06:30
  SPEAKER_03: And uh, and so I kind of was like, oh, I love this.
• 1:06:33
  SPEAKER_03: I love doing research.
• 1:06:34
  SPEAKER_03: I love you know what my mentors are doing.
• 1:06:36
  SPEAKER_03: This is I feel like this is a job that would be really fulfilling.
• 1:06:39
  SPEAKER_03: And I was like, I'm gonna be a professor, but there were so many hoops that had to be jumped through to make it to that end.
• 1:06:46
  SPEAKER_03: And I think, you know, being flexible, having a plan, but still being flexible is kind of the number one thing.
• 1:06:53
  SPEAKER_03: But I I wasn't intimidated by the change and I wasn't scared.
• 1:06:58
  SPEAKER_03: I was really, really excited because I really loved it.
• 1:07:01
  SPEAKER_05: Turn Loptimus.
• 1:07:02
  SPEAKER_03: Yeah.
• 1:07:03
  SPEAKER_05: Yeah.
• 1:07:04
  SPEAKER_03: Exactly.
• 1:07:04
  SPEAKER_05: Hey, what what's the what would you say looking forward?
• 1:07:09
  SPEAKER_05: How are you sort of framing your goals when it comes to what you're looking to find next?
• 1:07:15
  SPEAKER_05: You know, if you could, if we look 10 years from now, what are you hoping to answer?
• 1:07:21
  SPEAKER_03: So in my own lab, that's why we started moving into getting the these human tissues.
• 1:07:29
  SPEAKER_03: Because I feel like we need to be able to figure out what is this, what do these cells look like in a human?
• 1:07:36
  SPEAKER_03: How do they behave?
• 1:07:37
  SPEAKER_03: Are there things we can learn about them?
• 1:07:39
  SPEAKER_03: My lab does a lot of work with imaging, microscopies.
• 1:07:42
  SPEAKER_03: I love images.
• 1:07:44
  SPEAKER_03: I love imaging so much.
• 1:07:45
  SPEAKER_03: Uh, dark rooms in the cold.
• 1:07:48
  SPEAKER_03: That's where we spend most of our time.
• 1:07:51
  SPEAKER_03: But um, you know, we often are even looking at single cells dividing or move, you know, as well, which is amazing.
• 1:07:57
  SPEAKER_03: And there's a lot to be learned about how they behave in a dish.
• 1:08:00
  SPEAKER_03: There's a lot to be learned about the different types of testing that we can do to say uh say something about their identity and associate what they are capable of doing as well.
• 1:08:11
  SPEAKER_03: And and people aren't doing that right now, whether they don't have the tools or they don't have the experience.
• 1:08:16
  SPEAKER_03: It's not happening.
• 1:08:17
  SPEAKER_03: And I feel like if we can do that, that can make it easier for us to find these cells in the human brain, in a live person, to be able to start to understand how they're functioning in the human.
• 1:08:26
  SPEAKER_03: And that's where I think our field's going.
• 1:08:28
  SPEAKER_03: And hopefully our contributions will be, you know, helping that along.
• 1:08:32
  SPEAKER_05: And and do you think that will ultimately lead to the ability to sort of slow down cognitive decline for most people, or is that too much of a I mean, just just by altering adult neurogenesis?
• 1:08:46
  SPEAKER_03: I mean, I don't think most of the things that you would do to increase neurogenesis are incre improving functionality of other parts of the brain.
• 1:08:54
  SPEAKER_05: Yeah.
• 1:08:55
  SPEAKER_05: And and certainly But neurogenesis doesn't just apply to the hippocampus, right?
• 1:09:00
  SPEAKER_03: Well, again, this is this debate.
• 1:09:02
  SPEAKER_05: This is No brain debate.
• 1:09:04
  SPEAKER_03: Well, I so in there's another region in the mouse that is well studied, uh, and and and even another that that is you know somewhat studied.
• 1:09:13
  SPEAKER_03: So in the and the lateral ventricles, this won't mean you know much to most people, but in a different region of the brain, and also the hypothalamus.
• 1:09:21
  SPEAKER_03: But these are less uh uh known in a human context.
• 1:09:26
  SPEAKER_05: The brain's just gonna be the last thing we truly understand, do you think?
• 1:09:29
  SPEAKER_03: I think so.
• 1:09:30
  SPEAKER_03: It's it's hard to get everything is wired in so many ways it's that it's hard to learn how that how this neuron, what it connects to, and what it can influence, and what influences this.
• 1:09:41
  SPEAKER_03: This is actually gonna be very complicated to understand and between humans, right, as well.
• 1:09:46
  SPEAKER_03: And expensive, exciting, but so exciting.
• 1:09:48
  SPEAKER_05: Yeah, very exciting.
• 1:09:49
  SPEAKER_03: I love not knowing.
• 1:09:50
  SPEAKER_03: That means there's so much we can we can do, and you can be the one figuring out you know, how does this work?
• 1:09:57
  SPEAKER_05: What's the unanswered question you wish you could answer right now?
• 1:10:01
  SPEAKER_03: Related to my work, or just I mean we can give a personal answer as well if you want.
• 1:10:07
  SPEAKER_03: Oh, I this is I I don't know that there's one that's kind of like saying, like, what's your you know, favorite thing?
• 1:10:16
  SPEAKER_05: Resources, headcount, or would you like to what would you like to solve?
• 1:10:21
  SPEAKER_05: What would you like to answer?
• 1:10:23
  SPEAKER_03: I mean, just trying to understand how different parts of the brain talk to each other sounds simple, but it's so difficult in a human to understand.
• 1:10:35
  SPEAKER_03: And and I I think I would want to do this at the cell level, yeah, on how this cell talks to this cell, talks to this cell, as opposed to what we kind of have right now, which is that there's there's oxygen here, there's glucose uptake here in this region, but we don't know at the level of how is a cell talking to each thing and how that goes wrong in a disease.
• 1:10:56
  SPEAKER_03: That what is that factor that just starts the ball rolling?
• 1:11:01
  SPEAKER_03: Yeah.
• 1:11:01
  SPEAKER_03: Um, because a lot of people, you know, have mutations for disease, but don't always get the disease.
• 1:11:07
  SPEAKER_03: And so, like, why?
• 1:11:08
  SPEAKER_03: Yeah, what is that thing that just like starts the ball rolling that gets you going down the path and and is that reversible?
• 1:11:16
  SPEAKER_05: But you can't And is it the same for everyone?
• 1:11:18
  SPEAKER_03: And is it the same for everyone?
• 1:11:19
  SPEAKER_03: But you have to know how they talk to each other and how they behave at a single cell level and how you know how that circuit works to be able to understand any of these processes.
• 1:11:27
  SPEAKER_05: Do you think some of these AI models are gonna help expedite that?
• 1:11:30
  SPEAKER_05: Oh feels like a bit of a data problem if you have enough imaging.
• 1:11:34
  SPEAKER_03: You have to have enough information to feed into AI, and I feel like we just don't have enough information as of right now to feed into AI.
• 1:11:42
  SPEAKER_03: I think there's been a lot of really beautiful work done by the Allen Institute in Seattle.
• 1:11:46
  SPEAKER_03: Yeah.
• 1:11:46
  SPEAKER_03: And I think you know, they're doing a lot to be able to provide information um about you know different cell types, different neurons, how they talk to each other, how they're working together in different types of brains, disease or not.
• 1:12:00
  SPEAKER_03: So there is a lot of new input that's being generated.
• 1:12:03
  SPEAKER_03: But I just don't think right now we have enough information to train, to train a system yet.
• 1:12:09
  SPEAKER_05: Yet.
• 1:12:10
  SPEAKER_03: Yet.
• 1:12:11
  SPEAKER_03: You know, sometimes I think it's useful.
• 1:12:13
  SPEAKER_03: People people know we do research, but people don't know what it takes to do research.
• 1:12:19
  SPEAKER_03: And that's actually one of the problems of today is that, you know, you know, when funding is being cut, for example, what does it take to be able to do this research?
• 1:12:27
  SPEAKER_03: Like what does one have to go through to be able to get a grant, to get funding, to do the work?
• 1:12:33
  SPEAKER_03: People don't necessarily understand.
• 1:12:35
  SPEAKER_03: And and I think it's, you know, sometimes people think, oh, they're just throwing money out to anybody.
• 1:12:40
  SPEAKER_03: And actually it's so much more difficult and complicated and long as well.
• 1:12:44
  SPEAKER_03: So sometimes, you know, I and this might not be useful for this podcast, but I think it's useful for the general public to understand what does it take to be a scientist?
• 1:12:55
  SPEAKER_03: What does it take to get funding?
• 1:12:56
  SPEAKER_03: What how you know, what do you have to do to be able to do the research you keep talking about?
• 1:13:01
  SPEAKER_05: And I think that's such a good point because as from the outside looking in, and I'll often think this, even knowing what I know, how I get to work a lot with these different um uh research institutes.
• 1:13:15
  SPEAKER_05: It's it's frustrating because we're like, can you do this?
• 1:13:17
  SPEAKER_05: Can you answer this question or or study this thing?
• 1:13:20
  SPEAKER_05: Because we know there's so much reward if we got the answers to this, and then I could finally do the thing to help my parents or to help my grandparents or kids.
• 1:13:28
  SPEAKER_05: I think one thing I didn't lean into enough earlier, which I would like to circle back to is some of these um stem cell clinics.
• 1:13:41
  SPEAKER_05: Like the firstly, what's the reason why we can't do them here?
• 1:13:46
  SPEAKER_05: And I think I already know the answer to that.
• 1:13:47
  SPEAKER_05: But secondly, is there any efficacy, is there any thread of science that injecting stem cells is good for rejuvenation or inflammation or tissue damage?
• 1:13:56
  SPEAKER_03: Uh so at least mechanistically.
• 1:13:59
  SPEAKER_03: I think going back to kind of my lesson I gave a little earlier, that certain that stem cells make certain things would answer some of this question.
• 1:14:09
  SPEAKER_03: So right now, you know, the stem cell therapies that are FDA approved or you know, clinical trials are mostly all associated with the blood system, so hematopoietic system.
• 1:14:21
  SPEAKER_03: And there seems to be a lot of promise there.
• 1:14:24
  SPEAKER_03: Um but and the other being like transplantation, you know, of those of these massive amounts of neurons that were dead dead in this one very specific region in Parkinson's, for example.
• 1:14:35
  SPEAKER_03: This seems to be promising, but that's like clinical trials, for example.
• 1:14:39
  SPEAKER_03: But just randomly injecting stem cells somewhere.
• 1:14:43
  SPEAKER_03: Well, what stem cells?
• 1:14:44
  SPEAKER_01: Yeah.
• 1:14:44
  SPEAKER_03: What is how do you know what stem cells they are?
• 1:14:46
  SPEAKER_03: What are you what are they making?
• 1:14:48
  SPEAKER_03: I mean, I don't want you to inject, you know, um a mesenchymal stem cell that might be going to make bone or fat or cartilage in a place where there should not be bone, fat, or cartilage, for example.
• 1:14:59
  SPEAKER_05: But if it was the correct stem cell, that makes sense.
• 1:15:03
  SPEAKER_03: But the problem is that I don't think that there's really a lot of good markers to say.
• 1:15:06
  SPEAKER_03: So some of these cells will only make fat.
• 1:15:09
  SPEAKER_01: Right.
• 1:15:10
  SPEAKER_03: So if they're not good markers yet to pull them out of different tissues, then now you inject that into your knee, you've just injected a bunch of stuff that's gonna make fat.
• 1:15:18
  SPEAKER_03: Is that gonna be a good idea?
• 1:15:20
  SPEAKER_03: Right.
• 1:15:20
  SPEAKER_03: So I I think right now the their only stem cell therapies that I think are actually um, you know, scientifically suggested to be useful would be these ones that are targeting much more specifically things in the blood, you know, even bone marrow, transplantation, things like that.
• 1:15:40
  SPEAKER_03: But I would not inject anything that someone called a stem cell um into any other part of my body just just because there's it's just unproven.
• 1:15:51
  SPEAKER_03: And no matter what they say, if it is not something, you know, that people think the FDA might be very, you know, restrictive in some ways, there's a reason for that.
• 1:16:00
  SPEAKER_03: And that's because we just don't know enough.
• 1:16:02
  SPEAKER_03: And the risk in the many of these cases, it's not like there's nothing to lose.
• 1:16:06
  SPEAKER_03: There's actually a lot to lose.
• 1:16:08
  SPEAKER_03: Uh, you know, the uh a person who got injection into the eye and then got fibrosis.
• 1:16:13
  SPEAKER_03: I mean, now they can't see in their eye.
• 1:16:15
  SPEAKER_03: Like there's a lot of risk in the end.
• 1:16:17
  SPEAKER_03: And so I wouldn't, I I there it's not harmless, I guess, is what I'm saying.
• 1:16:22
  SPEAKER_03: So yeah, there's some horror stories out there.
• 1:16:25
  SPEAKER_03: There's some really terrible horror stories out there.
• 1:16:27
  SPEAKER_03: And it's because, you know, we don't know what stem cells you've got, what can they make, and and where are you putting them?
• 1:16:36
  SPEAKER_03: You know, there's just not there's just not enough characterization out there right now to feel confident.
• 1:16:41
  SPEAKER_05: Could be though in the future, or what I think so in the future.
• 1:16:43
  SPEAKER_03: I think in the future people are working on that now, especially related to like bone cartilage, fat, and this and those types of stem cells, for example.
• 1:16:50
  SPEAKER_05: Musculoskeletal, I think, is probably the earlier.
• 1:16:53
  SPEAKER_05: Yes, exactly.
• 1:16:53
  SPEAKER_03: And I and they're working on it, but it's just a hard question right now.
• 1:16:56
  SPEAKER_03: And so there are a lot of people trying to get funding um, you know, to study this and be able to say, I can predict what thing you're going to make.
• 1:17:05
  SPEAKER_03: Yeah.
• 1:17:05
  SPEAKER_03: Um, but right now, still, no, I wouldn't do it.
• 1:17:10
  SPEAKER_05: Okay.
• 1:17:10
  SPEAKER_05: We got an audience question segment now.
• 1:17:12
  SPEAKER_03: Oh, interesting.
• 1:17:14
  SPEAKER_05: What should a family member know when they go through like post-spinal cord injury?
• 1:17:19
  SPEAKER_03: Okay.
• 1:17:19
  SPEAKER_03: So I it's been a while since I've worked in that area.
• 1:17:24
  SPEAKER_05: Great question.
• 1:17:25
  SPEAKER_05: Which audience member is that?
• 1:17:26
  SPEAKER_05: What's their name?
• 1:17:27
  SPEAKER_03: Uh the name is Charlie.
• 1:17:28
  SPEAKER_05: Charlie, love that.
• 1:17:30
  SPEAKER_03: Um, so I would obviously go to the experts uh who would be the doctors in this situation uh as well.
• 1:17:38
  SPEAKER_03: And there are certainly places in the country that are experts in spinal cord injury as well that are, you know, cutting edge.
• 1:17:44
  SPEAKER_03: There's been a lot known now about um this idea of keeping things cold because you're trying to shift the inflammation, for example.
• 1:17:53
  SPEAKER_03: There have been other types of clinical trials that are trying to modify the ability of those axons that were injured, the processes of those neurons trying to reconnect.
• 1:18:03
  SPEAKER_03: Um, that suggests that for some in some window, there's a lot of training that needs to be happening as well during those times.
• 1:18:10
  SPEAKER_03: Um, but that window of training is very specific as well.
• 1:18:15
  SPEAKER_03: But right now, there, you know, we don't, people are still not walking after spinal cord injury at the moment.
• 1:18:22
  SPEAKER_03: And so how do you, you know, find a clinical trial to get on, you know, trying to find the next technology or treatment that might give you some aspect depending on where the injury is, you know, diaphragm, uh, you know, or the ability to, you know, control your bladder or or things like this.
• 1:18:41
  SPEAKER_03: Uh, and there are people who are doing lots of novel things right now and a lot of clinical trials related to that.
• 1:18:47
  SPEAKER_03: So, so you know, my insight is really unfortunately not that of a doctor, um, but that there are a lot of people who know a lot about that.
• 1:18:57
  SPEAKER_03: And I would get immediately on a clinical trial in this case, because in this case, there there is a lot to lose.
• 1:19:04
  SPEAKER_03: Um, and and there is a risk reward shifts, then exactly.
• 1:19:07
  SPEAKER_03: It does shift.
• 1:19:08
  SPEAKER_03: And the window in which there are things that can be done it is usually acute.
• 1:19:14
  SPEAKER_05: Post injury, it's usually very acute.
• 1:19:16
  SPEAKER_03: Yeah, I I I mean that might change, of course, you know, over time, but uh especially, you know, when the football players would be injured.
• 1:19:24
  SPEAKER_03: There used uh in Miami, I think it was, they had people who would have like a cooling chamber to immediately put the player in to cool the system down to reduce the inflammation immediately.
• 1:19:34
  SPEAKER_03: Right.
• 1:19:34
  SPEAKER_03: And so you have in that context, you could um, you know, avert some really bad effects immediately by having that uh situation.
• 1:19:44
  SPEAKER_03: Obviously, everyone doesn't walk around with access to those types of things, but just to say, time points after injury, there's going to be very different things that you might be able to do.
• 1:19:53
  SPEAKER_03: But I would definitely try to get on any type of clinical trial that that might help regain some aspect of function early on.
• 1:20:02
  SPEAKER_05: And I think technology is going to help solve for some of these things at some point.
• 1:20:07
  SPEAKER_05: I mean, Neuralink is pretty impressive.
• 1:20:10
  SPEAKER_03: I mean, there's uh there's a group actually um in EPFL in Switzerland and Lausanne, and they have you know done this really fascinating um uh kind of transplantation of almost like a robotic setup a bit that allows uh patients to be able to get control and walk by driving uh you know, the this uh I guess I'm I'm gonna do a terrible job of the stuff.
• 1:20:37
  SPEAKER_03: Oh, is this like the exoskeleton?
• 1:20:39
  SPEAKER_03: Something like this, but it it's it's actually amazing.
• 1:20:41
  SPEAKER_03: And this has been now for years that they've been perfecting this and being able to have a couple of patients that they've been able to use it in.
• 1:20:48
  SPEAKER_05: So um I think you can only imagine is completely life-changing for people.
• 1:20:52
  SPEAKER_03: Oh, completely.
• 1:20:53
  SPEAKER_03: And also I can only imagine it's gonna get better.
• 1:20:55
  SPEAKER_03: I mean, this is just rudimentary right now.
• 1:20:57
  SPEAKER_05: So we're merging with technology, we're gonna be bionic.
• 1:21:01
  SPEAKER_05: We kind of already are to some degree, right?
• 1:21:03
  SPEAKER_05: Like we have a we're our phones are an extension of us, like we wear contact lenses and glasses, and true, you know, we have replacement knees.
• 1:21:11
  SPEAKER_05: That's kind of happening.
• 1:21:12
  SPEAKER_03: It's true.
• 1:21:12
  SPEAKER_03: I, you know, I think about my grandparents and what they saw when they were young to what they saw when you know they passed away, right?
• 1:21:18
  SPEAKER_03: And like what change in technology happened during that time.
• 1:21:22
  SPEAKER_03: And I always thought that was an amazing leap, right?
• 1:21:25
  SPEAKER_03: Kind of like pre-television, even to you know, only 10 years ago.
• 1:21:31
  SPEAKER_03: But I actually think our jump is gonna be way, way, way more.
• 1:21:36
  SPEAKER_03: I mean, I I got email in college, right?
• 1:21:39
  SPEAKER_03: So just even thinking about that is is hard to imagine a time, you know, before before that.
• 1:21:45
  SPEAKER_05: So well, and and that now we have AI and computational biology, quantum computing.
• 1:21:51
  SPEAKER_05: Yes, like I think it could be yeah, crazy out there for the best, though, right?
• 1:21:57
  SPEAKER_03: They'll always be a little bit not for the best, but yes, there's always some good and bad with everything.
• 1:22:02
  SPEAKER_05: Okay, mindful of your time.
• 1:22:04
  SPEAKER_05: I'm gonna ask you one more question.
• 1:22:06
  SPEAKER_03: Okay.
• 1:22:06
  SPEAKER_05: If someone were to just join this podcast right now for the last 60 seconds, what would you want to be the key takeaway for them?
• 1:22:18
  SPEAKER_05: What do you think would be the most valuable takeaway for them?
• 1:22:21
  SPEAKER_03: So related to stem cells, um be skeptical if if you're thinking about some type of treatment or transplantation, only do something that is FDA approved or a clinical trial, and don't give in to the hype.
• 1:22:35
  SPEAKER_03: Um, that for sure, related to that.
• 1:22:38
  SPEAKER_03: On the other side of that coin is know that there is a lot of potential related to research, related to future therapies from these amazing um cells.
• 1:22:49
  SPEAKER_03: And so I think the controversy that's been out there, um, you know, I I mentioned that the ones came from, you know, these donated in vitro fertilization uh uh uh blastocysts in the end, right?
• 1:23:04
  SPEAKER_03: And then this is offensive to many people, and and that's fine.
• 1:23:08
  SPEAKER_03: Um, but there now are these as ones that we can take from an adult.
• 1:23:12
  SPEAKER_03: I mean, obviously they may have mutations and changes, you know, that we that are not great.
• 1:23:17
  SPEAKER_03: Nevertheless, they're a great tool.
• 1:23:19
  SPEAKER_03: And so not all stem cells are created equal.
• 1:23:22
  SPEAKER_03: So, you know, uh when people hear it, sometimes they're like, oh, I'm against stem cell research.
• 1:23:28
  SPEAKER_03: And and there is a side of this that doesn't have as much controversy, and I think one could see the benefit that they would have for sure on on research and potential therapies.
• 1:23:38
  SPEAKER_03: So I guess that would be, you know, don't demonize them and yet don't get the therapies right now.
• 1:23:43
  SPEAKER_03: Yeah, it's kind of a weird mixed coin.
• 1:23:46
  SPEAKER_03: Yeah.
• 1:23:47
  SPEAKER_03: Um yeah, related to uh, you know, cognition and and the thing that I study, I I think that just generally the idea of exercising, of having social interaction, of learning something new, of reducing stress, this is going to improve cognition.
• 1:24:10
  SPEAKER_03: And I think we all are aware of that.
• 1:24:12
  SPEAKER_03: We know we've done these different things before, and you know, sometimes vacation is does these things for us, sometimes it doesn't, right?
• 1:24:19
  SPEAKER_03: We know what the impact is uh if we incorporate it in our daily lives.
• 1:24:23
  SPEAKER_03: Those things can have long-reaching effects.
• 1:24:27
  SPEAKER_03: And and especially now as we get older, it's probably better to lean more into that.
• 1:24:32
  SPEAKER_03: I I've heard a lot of people who are like, if my legs go, they go, but I don't want to lose my brain, right?
• 1:24:38
  SPEAKER_03: And so if there is some kind of you know rolling rock that starts, you know, going down the hill, if we can keep that as something we integrate into our life early, maybe there's a way to stop, you know, the beginning of that rock rolling down the hill that could lead to eventual, you know, cognitive impairment.
• 1:24:57
  SPEAKER_03: It's a pretty good investment with very little best shot we have.
• 1:25:00
  SPEAKER_03: Yeah, exactly.
• 1:25:01
  SPEAKER_05: And who knows, we might be able to push that rock back up the hill at some point.
• 1:25:05
  SPEAKER_03: Uh I would never say never, but right now I don't see it.
• 1:25:09
  SPEAKER_05: Can we chop that in with Darcy just nodding and then cut?
• 1:25:14
  SPEAKER_05: Okay, the summary then be curiously skeptically optimistic.
• 1:25:20
  SPEAKER_03: I love that.
• 1:25:21
  SPEAKER_03: I feel like that should be you know my website for you know, logo for my website.
• 1:25:25
  SPEAKER_05: That could be the book.
• 1:25:28
  SPEAKER_05: Darcy, it's been a pleasure and a privilege.
• 1:25:31
  SPEAKER_05: Yeah, no, thank you.
• 1:25:31
  SPEAKER_03: I've loved having you here.