Exploring the Wild World Within
How do different cells in our bodies age differently? What exactly happens when a neuron takes out its trash? In this episode, neuroscientist Monica Driscoll takes Gordon on a tour through her serendipitous career. Topics include sloppy developmental biology, enigmatic exophores, worms in space, and the importance of studying things no one else is thinking about.
Distinguished Professor, Department of Molecular Biology and Biochemistry, Rutgers University
Monica Driscoll received her A. B. degree in chemistry from Douglass College in 1979 and earned a PhD in biochemistry and molecular biology at Harvard University in 1985, studying molecular and genetic regulation of gene expression in a yeast model system. She pursued postdoctoral studies in the lab of Dr. Martin Chalfie at Columbia University, where she began her work on the simple animal model C. elegans, focusing on deciphering molecular mechanisms of mechanotransduction and necrotic neuronal degeneration. She joined the faculty of the Department of Molecular Biology and Biochemistry at Rutgers University in 1991, where she is currently appointed as a Distinguished Professor. Her lab now studies the basic biology of aging with a focus on molecular mechanisms of healthspan extension via genetic, chemical, and exercise interventions. Neuronal proteostasis and anti-neurodegeneration mechanisms are also major research interests.
I think actually in nature… you know, nature’s so chock full of, like, incredible, amazing, unexpected things. And all you have to do is kind of poke around a little bit and you’ll hit one…
Aging. None of us can escape. Like gravity, it pulls on each of us. Why do some of us age gracefully and others don’t? How do our bodies and minds experience aging the cellular and molecular level? Why do we even age to begin with? And maybe most importantly, can we do anything about it? My name is Gordon Lithgow, and here at the Buck Institute in California, my colleagues and I are searching for and actually finding answers to these questions and many more. On this podcast, we discuss and discover the future of aging with some of the brightest scientific stars on the planet. We’re not getting any younger yet.
Gordon: Monica Driscoll, what a pleasure to have you on the podcast. It’s always a delight to talk with you and I always learn a lot from you…
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…I just started reading a biography of E. O. Wilson. And there were a couple of striking things that were said early on in this — in this book, and it was the kind of advice he gave to-to young scientists. And one thing was — I’m paraphrasing here, of course “never study anything anyone else is studying, especially if two people are studying it already and they’re competing with each other. Go elsewhere.” And I look at the discoveries you’ve made and continue to make. And I seem like this is something — I don’t know if it’s conscious or not — but you live by this. Like, you’re constantly going to the new thing that no one else has really thought about or is working on.
Monica: Well, thank you. Yeah, I think, you know, I don’t, like, exactly have a policy [laughs] for myself.
Monica: Um, I should. But, um, but I think I’m just naturally more attracted to something that strikes me as being really weird. And to tell you the truth, I think, you know, part of it is I try to step back a little bit or not have exactly preconceived notions of how things should work. So, I feel like my eyes are slightly more open than the average bear to like, wait a minute, like, that doesn’t make sense or that’s super weird. And then I kind of gravitate to those sorts of things.
Gordon: I’d like to, if you don’t mind, go back to the beginnings of, you know, you’re a scientist. How did that happen?
Monica: [Laughs] Yeah. So, it was, you know, really a great, lucky accident. Really, truthfully, what I think one of my most formative experiences was when I was pretty young, um, I think someone read me the Dr. Seuss book, Horton Hears a Who.
Monica: And in that book, um, there’s this very large elephant with great sensitive ears. And he hears this little, tiny world on a fleck — a fleck of dust, which is full of all these little Whos and they-they have a whole world. No one can see it, um, and essentially you can barely hear it. That concept of, like, a whole entire world inside — that could be inside our world and not seeable, but somehow like- addressable and identifiable was just like — it was like a lightning bolt. Like, I was like, what? Like that can happen!? And so, you know, I started doing, you know, the little kid things: cracking rocks, looking at bugs. I had great things like, yeah, I remember the invisible man and a chemistry set. But I didn’t really have a sense of a research career. And so, I went to college. I started college to be a medical technologist. That was going to be my thing.
Gordon: Was-was chemistry and biology at the same time of interest to you or was — were you going down —
Monica Driscoll: Um.
Gordon: — that chemistry path?
Monica: No. You know, the truth is, like, biology was always more interesting. But, um, but ch– the chemistry people were pushing me. And then in, um, when I was a junior taking biochemistry, kind of the same thing was happening. I was doing really well in biochemistry. And I got — I had an exam. I had two things wrong on this exam, and they were related to each other. I totally screwed up on that concept. But like, you know, the rest of it, like, you know, I got a good grade. Like, come on. But I get the paper back —
Monica: — bright red, see me, underline, underline, underline, from the professor, which is absolutely, absolutely horrifying.
Monica: And I debated, you know, what’s more — what’s the more cowardly or more embarrassing thing, not to show up or to show up and have to deal? And so, I decided that I had to, you know, show up and deal. And I went into his office and he’s like, “Where are you going to graduate school?” And I was like —
Monica: — you know, like, “What?” And, um, so he really encouraged me to apply for graduate school. I applied, um, I end up entering a program at Harvard. And, um, then that, you know, and then I just, you know, more and more in love with the discipline, like, every day.
Gordon: You had incredible mentors like starting with Helen Greer at-at Harvard. Uh, tell me a little bit about that experience. And you’re working on yeast, right?
Monica: Yeah, so-so I started, um, working on yeast, and it was such a super exciting time. Like, actually, Lenny Guarente was-was working in the [Patasony] Lab at the time, just kind of starting to-to engineer, um, yeast and, you know —
Monica: — think about these-these fluorescent reporters which, at the time, weren’t really fluorescent. They were the beta-galactosidase reporters and-and —
Gordon: Yeah, yeah.
Monica: — what a promoter was. And it was — it was kind of super exciting.
Gordon: Something that’s come up in-in-in some of our podcasts as, you know, the utility of model organisms and things like this. And, yeast is obviously an amazing genetic system and it’s so easy to do things fast. Um, but you-you actually did the same transition that I did. I was working on —
Gordon: — yeast as well. And I moved into-into C. elegans. And-and when you did that, you were doing postdoc work in Marty Chalfie’s lab, a-a name that, I’m sure is familiar to-to some of our listeners. Marty, of course, eventually was awarded the Nobel Prize for, his work on fluorescent, green fluorescent protein, and what an incredible tool. Were you conscious at the time that this was a lab that was likely to run into this kind of —
Gordon: — fame? [Laughs]
Monica: [Laughs] Um, you know, like, I would say that, you know, I definitely think Marty had the mind, the prepared, um, minds to kind of mix these two disciplines. Um, you know, I was in the l–I essentially, you know, had just left the lab to start my faculty position when all of this was coming down. And we had a strain problem– a strain crisis. So, I went to New York to get some strains. And Marty was showing me the first, like, the bacterial clone glowing green on this plate. And I was like, you know, whoa. I didn’t at the time kind of appreciate how, you know, completely marvelous and how this, you know, how this was going to revolutionize all of biology. But, um, but it was way cool. And Marty, you know, would do these creative, way cool things. So, you know, definitely in his wheelhouse.
Gordon: So , the origins of that protein was from where?
Monica: So, um, so, that is a jellyfish protein. And I’m sure there are accurate written accounts of how everything went down. But my impression, um, just to, like, super paraphrase, shorten it, is that Marty was at some lecture at, you know, on jellyfish proteins at Woods Hole or something. And he just, you know, happened to stop into this lecture and, you know, happened to get the idea, hey, wouldn’t it be fun to, you know, check that out in a worm? And, um, then the rest is history.
Gordon: Yeah, it’s incredible. And it’s used in-in-in every aspect of biology. We-we see these fluorescent proteins as-as indicators of the presence of proteins, the changes that happen in proteins, the location differences.
Monica: And, um, there was — Marty had identified this strange genetic mutant that had dominantly inherited neurodegeneration. And at the time, you know, this was really one of the first models of this happening so, I, you know, I sought to clone that. I don’t even — I don’t remember how long it took, but it took a long time. But when it did, it paid off. Right? When I did, it paid off. Because, um, it turned out that that particular, um, protein, we could understand how it caused neurodegeneration and how it hyperactivated nerve cells similar to what happened in stroke. But what — but also, it was like a total marvelous double whammy because it turned out to be in this, um, ion channel that, um, its normal job was for mechanical touch sensitivity, touch.
Monica: And so, no one had that channel, either. So, um, I feel like I’ve been, like, very lucky in, um, a lot of, you know, my science bumbling around. Um, I, I think actually in nature, um, it is so, you know, nature’s so chock full of, like, incredible, amazing, unexpected things. And all you have to do is kind of poke around a little bit and you’ll-you’ll hit one, um, or two or three. But I feel like I have been, you know, kind of lucky to fall upon these various things.
Gordon: So, in –I guess your early studies came down to studying necrosis. Necrosis versus apoptosis, which I guess people thought at the time was a more program process. Very much [conserved] between-between mammal — mammals and-and worms, which was incredible, one of — one of the early indicators. But ne-necrosis apoptosis, can you explain the-the differences and similarities?
Monica: Right. So you might think of apoptosis as a, um, kind of orderly program for a cell to commit suicide and be surgically removed without, um, provoking any other action from the cell. So, let — you can envision that maybe the cell had a purpose in development, or maybe it’s just better to get rid of it for subsequent survival of the-the animal later. But, um, this — these were something — things that were kind of selected for and programmed in. On the other hand, necrosis was considered a disordered response to extreme physiological conditions or, um, injury, something that actually wasn’t really planned, but obviously could be a problem for-for an animal which is losing cells. And kind of the key feature of necrosis, um, especially in higher organisms, is that it invites, um, the signaling or release cell contents attracting macrophages and all the-the immune system, and actually end up causing, um, a fair amount of tissue damage. And so, you — if you want to go to the ends of the extreme, apoptosis is nice and orderly and in-intended in development. And necrosis is more, um, like, oh dear, there’s a bad problem here, and, um, it needs to be controlled on the short term or things are going to get worse because the body actually has a — has a severe response to it. We were able to show that, although necrosis might not have been programmed, per se, we could — we could get genetic models that program it. And then we could identify genes that were critical for the execution of that-that death and, um, go ahead and-and, you know, identify what the proteins are, what the problem was, and we’re able to kind of track a-a calcium crisis, um, that happens in these in-injured cells. And the idea is that, um, understanding this process will give us, um, some insight and handles to things that happen, um, terrible things that happen to humans, for example, when cells are dying and neurons are dying in a stroke of oxygen deprivation.
Gordon: Mmm. Uh, is necrosis the dominant feature of cell death in aging?
Monica: Uh, that’s a good question. I say no. Um, [laughs] surprisingly, so this is where we started. Um, yeah, I had this, like, you know, great idea that with age,cells are dysfunctional. They can become injured, per se, just really, you know, from the inside or the outside. You know, and that-that cells would be dying all over the place, um, possibly not from apoptosis, but from a necrotic kind of injury sort of death. This was like, oh, what a great idea, you know? No one’s study — No one’s doing this.
Monica: Like, let’s check this out. So, um, so, we go ahead. And-and really the way I got into the aging field, um, was really kind of through this question. But I was like, well, the answer’s so easy. All we have to — Because the necrotic cells actually look swollen. So, the easy thing to do would be to just look at the animals. But we wanted to do something easier. It was like, oh, this, you know, this has to be in the literature. Right?
Monica: Um, and then, you know, um, you know, start looking through. And I was like, wait, you know, people were super interested in longevity genetics and for good reason. But, like, it really struck us coming in — this is my specialty, coming in naive to-to say like, why isn’t anyone, like, looking at what’s happening to these tissues while the animals are aging? And so, we ended up doing this-this kind of, I mean, very basic study of, like, looking at kind of just the features, like just describing, um, what happened to the — to the animal as it aged and because-because it was a long time ago or [laughs] no one else had done it, it turned out to be really, you know, important to do that and to start to think about these ideas of different tissues with different susceptibilities and understanding like what actually goes wrong in the animal, um, as-as it’s aging and ultimately dying.
Gordon: I mean, this-this was a super important, um, discovery that contribution that you made to the aging field. Just to take one step back. I mean, when you started to hear about mutations that extended lifespan in this organism that you happened to be studying neurodegeneration in, did you — did you believe them?
Monica: Um, so, I thought people were doing, you know, reasonable longevity, um, longevity types of assays, and so, I actually thought it was really exciting and cool. I know that, you know, again, at the beginning of the origins of the C. elegans aging field, people, probably including yourself, took a lot of heat about what was the nature, you know, what was the nature of these aging genes. And part of that was that it-it took a long — same thing — took a long time to, um, to clone these types of genes and — by the methods that were available at the time. Um, and so, yeah, I’m not sure what else I would-would say there other than to say I thought it was, like, very cool. I never thought I’d actually really be studying it.
Monica: Like, you were — you were ahead of me in this. You were doing longevity genetics, right?
Gordon: Well, and you were ahead of everyone in what you just described, the fact that you said that, you know, asked a simple question, what’s actually going on in these worms? Let’s just look at them.
Monica: Right, right.
Gordon: So, you know, obviously many people who-who study C. elegans are-are working on developmental processes. And development in the worms are a very regimented process. We know exactly what cell, you know, divides into what cell and so on. When you started to look at this, call it, noise, that’s happened during aging, does it tell you something about the evolutionary origins of aging in contrast to development?
Monica: Uh, so, that’s-that’s a really interesting question. And we’ve, um, again, you know, we kind of think about it and talk about it. Um, I kind of really like this idea of antagonistic pleiotropy, which is this idea that in natural selection, you have the driving force is getting, you know, reproducing and making, you know, the next generation of that particular animal. And so, there’s a very strong force that drives, um, what, you know, kind of order and use and utility and importance and conservation, and all those things happen. And, um, but what happens then is that the animal reproduces, everything has done its thing. But then worms like us can live for longer. And there was no reason for that worm, for example, to turn off its developmental programs. Right? The developmental programs. Just, like, you don’t have to be neat and clean anymore.
Gordon: Yeah, yeah.
Monica: And so, the developmental programs wouldn’t shut down. And then, you know, there’s good evidence in the field now that it was just left on. Um, kind of can be deleterious because it’s not neat and orderly and efficient and things like that. But the variation that you see later, I think can in part be, um, attributed to this kind of sloppy “leave on” of the developmental programs. And which also, like, is very fascinating.
Gordon: Actually, I had a — I had a friend, who had a British sports car, and he couldn’t turn the engine off. So-
Monica: Yeah. [Laughs]
Gordon: We go — we go on rides, we get out the car, and we’d hope to get back to the cars i-if it still had gas left in it. [Laughs] So, I had to think of it like that, yeah. Um, so actually, you’re hinting at something I wanted to talk about, which is that you’re also very interested in the molecular cellular processes of aging as well at a deep level. And I mean, there’s many things that we can talk about here. But what is “exophers” and this sounds like a great title for Netflix latest science fiction movie/series: “what are exophers?”
Monica: So, in my lab, we are very interested in, um, you know, for example, the aging of the nervous system. And we had a project. So, way cool about C. elegans is that you can label individual neurons with a fluorescent probe, and then you can, um, or gene reporter. And you can watch that neuron, the entire lifetime of that neuron, really from its birth until the animal dies. Like, that is so awesome. And don’t even think about doing that with a human. Right? (So, like, you know, “no!”) So, again, like, you know, very simple- we’re just looking at individual neurons as they age. And at Rutgers, our undergrads have to do, um, research in order to graduate.
And so, I had this wonderful undergrad in my lab, And, his job was to really kind of count these branches and bubbles and things that were changing, and were changing at a fair frequency. So, he had this labeled strain that actually, I have to say this. Uh, the strain also, um, that we discovered this in was literally in the garbage. And [laughs] we took it out, um, because it was — it was a strain that expressed, um, a red marker called mCherry at a really high level. And it just seemed to be like, too high an anomaly. And it was like, wait a minute. Like actually, maybe that-that’ll be an interesting thing. Like, so, take it out of the trash, and yeah. Anyway —
Monica: — he was looking [at] the trash strain. And, um, he comes into my office and he says, “Monica, you know, I’m seeing this — I’m seeing this bizarre material, this mCherry, that’s clearly outside of the neuron.” And I was like, “Oh, that’s interesting.”
Monica: “Um, how often are you seeing it?” And he said, “Oh, like 5, 10 percent of the time.” And I was like, you know, hmm. Um, and with PI wisdom, I said, “Well, you know, I think it’s super interesting. But, like, I don’t know how you’re going to make a story easily out of something that’s happening 10 percent of the time. You know, go back there and count these things that are happening 40 and 50 percent of the time.” So, luckily, he doesn’t listen to me. And he —
Monica: — really wants to know where these little crazy things are ha– that are outside of the neuron are coming from. So, we didn’t even have a timelapse photography setup. He came to the lab and stayed the entire night taking a picture every 15 minutes to try to catch one.
Monica: And the first night he didn’t catch one, because they’re rare. Right? Um, then he went home and slept and came back like a day or two later. The second night, he didn’t see anything. Um, didn’t catch it. But on the third night, he caught one forming! And he comes into my office with this-this like crude, yes, but this movie of a neuron taking its garbage, this mCherry that it doesn’t want and, like, pulling it all to one side, making this ginormous exclusion, and just throwing it away! And I was like, it was another one of these moments. It was like the Horton Hears a Who moment. It was like the lightning went through my scalp. And —
Monica: — and I was like, holy mackerel! Because, um, as you know, in human neurodegenerative disease, it’s now appreciated that aggregates in neurotoxic entities are eliminated from cells and spread from –
Gordon: Hmm, yes.
Monica: — one cell to another. And this is you know, increasingly appreciated as a — as a core component of the pathology in disease. And so, same thing. Like, very difficult to look at and study in the context of the human brain. But in the worm, like we — this is like a — like, again, like a gift from, you know, the biochemist god in heaven. It’s like — it’s like, wow, we can dissect this incredible orchestrated process and identify, you know, what are the conditions that provoke it? What is the cellular molecular gear that, you know, ident– How do you identify the trash? How do you collect it? How do you store it? How do you decide to throw it out or not? What happens to the trash once it gets out of the neuron?
Gordon: Mm-hmm, mm-hmm.
Monica: Can we follow the other part of the equation, which we’re doing, um, in collaboration with Barth Graham, who’s fantastic cell biologist colleague here in, um, MBB at Rutgers. And it’s just, um, so, it’s like — it’s just wonderful. Um, and it’s really — Andso, when we started talking about this, um, so many people in the field said, “Oh my gosh, we’ve seen these things! We’ve seen these things!”
Monica: And, but Illia was the one who had the, you know, who wanted to actually, you know, use a scientific approach to identify what they were.
Gordon: That’s a wonderful story. And-
Monica: It is a fantastic story.
Gordon: So, any grad students out there listening to this podcast, please do not listen to your PIs under any circumstances!
Monica: Right. Never listen. Uh, no. I mean, you — Have a dialogue. I mean, we argue about science all the time. And then people get to decide what experiments they want to do. And that’s the way things move forward.
Gordon: So, another mechanism that obviously studying is clearly important in worm aging, and maybe in aging in general, is this mechanism of autophagy, which is — And I guess, you know, I’d like to hear, you know, what’s the relationship with exophers and autophagy, if there is any.
Monica: Right. So, that’s a super interesting question. Autophagy is this other mechanism that, um, recognizes trash in aggregates, and it helps kind of, um, the gear can help collect and then just, you know, bring to lysosome and get rid of that. What we did is we kind of crudely knocked down the autophagy genes and found that when we, um, disrupted proteostasis in that way. So, you think you get rid of trash removal r– mechanism, you increase the trash load. This actually increases exophers, mostly. It’s possible that there’s a very specific molecular connection or even a switch and it’s a paper that, um, that we’re working on now.
Gordon: Fantastic. Oh, thank you for that.
Monica Yeah, so that’s like a really nice collaboration with, um, with the Buck (Institute).
Gordon: [Laughs] That’s great. Um, there — with the limited time we have, there’s two things I have to mention.
Gordon: Uh, one is the drug called metformin. The —
Gordon: And, the second is space.
Monica: [Laughs] Yes.
Gordon: Let’s do space first.
Monica: Okay so,….
Gordon: You sent worms into space, right?
Monica: So, right. So, you know, I’m talking myself into buying a lottery ticket now that I’m hearing my life story, because this was also a super lucky thing. Like, we had — we had been interested — It started really — it was anchored in the aging studies. And we had, um, been interested in-in how, um, muscle declines with age. And this is like a uniform, um, phenomenon that occurs in-in multicellular organisms, you know, across everything. And so, we had just like, you know, published some stuff where we’re talking about this stuff. And of course, muscle decline is a huge problem in — for space — for individuals who are in space for extended periods of time. Because —
Monica: — your muscles degrade really, really fast. And you can forget about going to Mars unless, you know, something can be done about this if you’re a person. Um, so-so anyway, NASA is kind of interested in this. And we had colleagues — Actually, there were colleagues — so, again, very lucky connection — who were engineers, really, and did microfluidics engineering and stuff. And they had worked out kind of like with our enthusiasm behind them this method for measuring how strong worm muscles were.
Monica: And I think they had some connection to Nate, I think it’s Szewczyk…
He’s Polish with all consonants in his name, so my apologies, um, for mispronunciation. But, um, so Nate was, um, had been involved with NASA. And they were sending something up to the International Space Station to study muscle decline.
Monica: And they had some extra spa– extra bags of, you know, free to send things up. So, they just — they invited me, to-to, you know, design some experiments to send stuff up to the International Space Station.
Gordon: That’s fantastic.
Monica: And so, we thought about what had been done. And there had been this huge emphasis on muscle. But of course, neurons are the other part of that equation. And so, we sent up a number of strains that had markers in the muscle — I’m sorry, in the neurons. And, you know, same thing. And the other thing is people were looking at development. We kind of wanted middle age as like, you know, astronauts, they’re middle age. Uh, or young. Okay, they’re young, butthey’re adults. And so, we wanted to look over adulthood. And-and so, that was the experiment we did. And we got — we actually got a surprise. We did see some neuronal restructuring. That was kind of interesting. But we also sent up this exopher strain And, um, we found what was happening in, on earth, um, that garbage is very nicely managed by the neighbor, um, in a glia like interaction. But in the International Space Station with microgravity, that trash is handled very, very poorly. Like the — either the transfer doesn’t happen, or certainly the degradation in the second cell is not happening.
Gordon: That’s amazing.
Monica: And that was a, you know, total shock. Like what!?!
Monica: Um, but it was so clear.
Gordon: That’s crazy. You can’t imagine that, yeah, a-a-an organism that’s a millimeter in size is subject to microgravity effects. That’s amazing.
Monica: Right, right, right. So, super, super, super, super fun. Um, yeah. So, but again, it was just like luck or, you know. Talk about science always and good things happen. Right?
Gordon: Yeah. The prepared mind.
Gordon: Um, well, let me ask you about metformin. And the reason why I want to ask you about this is obviously, um, many of our listeners, I think, are very aware of how, um, prominent this is in the aging field in terms of potential clinical trials that are likely to happen soon. Also, it’s a FDA approved drug that’s been, you know, millions and millions of doses have already been used in a very safe way. You were one of the pioneers that pointed out that this compound was also potentially involved in aging.
Monica: Yeah. So, um, yes. And to tell you the truth, [laughs] I don’t even know where this — where that came from. But we were, you know, we, like anyone in the aging field, we’re really kind of, um, interested in metformin. I think that part — that our, um, we had a little exercise project. And I think the connection there was metformin was proposed, to be, um, kind of engaging pathways that were exercise mimetic.
Monica: And so, I think that was our — that was our entry. But we — So, we got, something — You know, we started thinking, well, people don’t exactly know how it’s working. You could use worm genetics. And Brian [Unintelligible] the lab started, you know, both looking at sensitivity and identifying, a number of, um, I don’t know, I guess I would call them kinase transducers, that were required, um, both for longevity and for health, um, benefits. And these are kind of fam– like, you know, famous anchor things like AMP kinase, um, which is really a core, um, I don’t know, I guess I would say a — I, on whole, antiaging kind of, um, activity, but of course, really complicated, you know, connected to everything, and things need to be done right. Um, balance is everything. Right? So, that was it. And then kind of fast forward into this wonderful collaboration that we have with, your group and with Patrick Philip’s group at the University of Oregon where we’re looking for reproducible and robust interventions that extend both the length of life and the quality of life. And metformin obviously was of great interest for that. And so, you know, kind of unleashing this into the non-disease human population is always, you know, there’s always a concern but that’s like a whole other story. Um, the main point being, we can, again, kind of take a reductionist approach using diverse Caenorhabditis strains. So, there are strains of C. elegans, for example, that come from all over the world. There’s hundreds that have been collected. And they have — they together represent an amazing genetic diversity, as much as you have among the human population. So, we can model the diversity, too, which is a key question you want to know about when you introduce a drug into a population. How kind of uniformly will the response be visited or, you know, how, you know, like 10 percent of the people? 90 percent of the people? We need to know that. And in this case, um, we found — we found super encouraging information in the Caenorhabditis genus. So, in those strains we saw both, like, pretty remarkable increase in lifespan and the locomotory health span. Um, but that was not the case in some of the other species that were — that are a little bit more distant. But, also raised the, you know, kind of raised the red flag that, um, the genetic background and the, you know, kind of ultimately as I’m sure we will really appreciate in the upcoming decade, the personalized medicine component is probably going to be something that’s important and needs to start to get on the radar, also.
Gordon: Wow. Yeah. Like absolutely! I mean, this is super important. And I know this goes across all of clinical trials and all of biomedicine, like how do you select the group of people you’re going to do tests on. And-and —
Gordon: — and-and this definitely speaks to it. And maybe-maybe possibly working out the mechanisms as to why some genetic backgrounds respond and some don’t, perhaps?
Monica: Right. Right. And so, really with modern tools, you know, there are responders and non-responders. And this gives you the handle on kind of figuring out what seems to be — what are the important candidates and not. And then pretty easy to test that.
Gordon: Yeah. So, I mean, I guess, um, many of us are thinking, wow, how lucky are we that, you know, we mess around with worms and yeast and flies and so on. And maybe suddenly we realize that there is real relevance for human health in the future. What do you think about that? Do you think we’re really going to be able to translate the biology of aging science project into actually, you know, altering human health?
Monica: Yeah. So, um, so, really great question. And of course, we think about this all the time. And, you know, I wonder if we’re, you know, I kind of think maybe we’re right at that point where we were, you know, two decades ago just looking at, like, apoptosis- does it, you know, is it — is it relatable from worms to humans? And then it causes a revolution in biology. This could happen. It could also happen the other way. But basically I feel like the track record of invertebrate genetics has been so strong to inform, you know, not necessarily on you know, like, okay, metformin’s going to, you know, make humans be perfect you know, exercise specimens or something like that. Probably not going to happen. But what is going to happen is the associated things that we find, we’re going to find, oh, this particular compound is really wonderful. And I think, you know, Gordon, I know you have a really nice example in your lab now of a C. elegans intervention that ultimately, you know, ended up being fantastic for mammalian bone. And, um, so the connections or the highlighting of these conserved components of biology I think are going to translate in really exciting ways.
Gordon: That’s great! I think that this is something that many of us in the field are-are really, um, completely behind now and-and, are very optimistic about. And I think we will transform medicine.
Monica: Let’s do it.
Gordon: Well Monica, it’s been delightful to-to have this opportunity to talk with you. Thank you. The time’s been really fast. [Laughs]
Monica: So great to talk to you, as usual. Yes.
Gordon: And-and-and thank you for your discoveries, your future discoveries, your mentorship, and, and, hope to speak to you soon.
Monica: Yes. Thank you so very much.
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“We’re not getting any younger, yet!” is made possible by a generous grant from the Navigage Foundation. The Navigage Foundation is enhancing the lives of older people through the support of housing, health, education and human services. Our podcast is produced by Vital Mind Media: Wellington Bowler is here with me using sign language to keep me on course and recording the podcast. Stella, who I love spending time with talking about science, as you know, is our editor with the Creative Direction of Sharif Ezzat and the Buck Institute’s very own Robin Snyder as the executive producer.
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