Live Long and Master Aging podcast

Episode

243

Are scientists being honest about aging research?

Prof. Coleen Murphy | Princeton University

BY PETER BOWES | SATURDAY FEBRUARY 10, 2024

Coleen T. Murphy, a professor at Princeton University, specializes in genomics and molecular biology and is the author of How We Age: The Science of Longevity.

In this wide-ranging interview we discuss the significance of declining cellular repair mechanisms that over time lead to visible signs of aging. Prof. Murphy has a particular interest in reproductive aging and cognitive function during aging, considering the former as an often overlooked aspect that begins midlife. Her work with the model organism C. elegans, a nematode worm, has led to important insights into the genetics of aging due to its short lifespan and visible aging process. She believes that translating such findings into mammalian models and eventually human applications is crucial.

Prof. Murphy also expresses concern about the way longevity science is portrayed and criticizes some researchers for failing accurately to describe the true implications of their work. She says there is a need for honesty and realism from scientists to maintain public trust, especially in the field of aging and longevity where bold claims can often outpace reality. Researchers, she insists, should not over-promise results that science cannot yet deliver.

We also address the potential for ‘exercise in a pill’ and Prof. Murphy highlights recent research indicating that certain proteins can rescue memory function in aged mice. She also argues that without taking care of our planet and its inhabitants, the quest for longevity loses much of its significance.

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Topics covered in this interview include:

  • Murphy provides her definition of aging, focusing on the declining efficacy of repair mechanisms. [00:01:15-00:02:25]
  • Personal motivations for engaging in aging research, emphasizing the interdisciplinary interest in aging and its impacts on human life. [00:02:43-00:03:53]
  • The central role of aging research in addressing a gamut of age-related diseases, highlighting a shared approach to dealing with these ailments. [00:10:36-00:11:29]
  • Skepticism around outlandish longevity claims arises, cautioning against eroding the public’s faith with unrealistic aspirations of reversing aging or achieving immortality. [00:13:55-00:14:18]
  • Lifestyle choices and their impact on longevity, including the practicality of harsh dietary regimens. [00:17:49-00:20:37]
  • Exciting translational research developments, where genetic discoveries in model organisms have potential pharmaceutical implications for extending human healthspan. [00:22:48-00:25:06]
  • The relevance and benefits of using model organisms such as C. elegans in aging research, and how these can lead to safer and more efficient human trials. [00:25:18-00:28:05]
  • Personal health strategies derived from research are touched upon, discussing the significance of exercise, diet, and emerging knowledge of mitochondrial health. [00:28:39-00:36:23]
  • Reflections on the need for a sustainable, livable world, tying the pursuit of longevity to the overall environmental and societal well-being. [00:41:58-00:42:54]

Connect with Prof. Murphy: Laboratory at Princeton University | Video: Profile | LinkedIn | Publications

Read: How We Age: The Science of Longevity


Discounts & Affiliation disclosure: This podcast is supported by sponsorship and affiliate arrangements with a select number of companies. The income helps to cover production costs and ensures that our interviews, sharing information about human longevity, remain free for all to listen

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TRANSCRIPT – – This interview with Coleen T. Murphy was recorded on February 6, 2024 and transcribed using Sonix AI. Please check against audio recording for absolute accuracy.

Coleen T. Murphy: We already have a sort of tenuous relationship with the public that is scientists, right? Many of us are trying to do the very best that we can and try to make sure that what we say is not outlandish and it’s actually realistic, and that our research, when we describe it, it doesn’t, like go way beyond what we can actually achieve. Because when someone promises you something and they don’t come through, they shouldn’t have faith in you. And so that, you know, this promising of things that are never going to happen really destroys the public’s faith in scientists.

Peter Bowes: Coleen T.Murphy is a professor of genomics and molecular biology at Princeton University and the author of How We Age: The Science of Longevity. Hello again. Welcome to the Live Long and Master Aging podcast. My name is Peter Bowes. This is where we explore the science and stories behind human longevity. So you can see why Professor Murphy’s book appealed to me. It is indeed a deep dive into a vast amount of research conducted over recent decades to try to better understand this thing called aging. Coleen Murphy, welcome to the Live Long and Master Aging podcast.

Coleen T. Murphy: Thank you for having me, Peter.

Peter Bowes: So it is a deep dive, and you approach many of the fundamental questions about aging. I would like to start with perhaps what I consider to be the most of fundamental of questions, and that is what is aging. I know there are a lot of different definitions from researchers and scientists, but what is your view on what aging is?

Coleen T. Murphy: Right? That’s a really hard question to answer depending on the level that you’re interested in. So, you know, we study the molecular and cellular levels of aging. But in a general sense, aging is what happens when we can no longer carry out the repair mechanisms that keep us young, so we can think of all the energy our body uses. A lot of that is used to repair, like repair all the damage in our cells and our DNA. And at some point those repair mechanisms stop working as well. And then the end result is, as we’ve all noticed, changes in our skin, our metabolism, our connective tissues. Right. So things that then ultimately result in us feeling older and, you know, experiencing aging.

Peter Bowes: Well, we’re going to dive a little bit more deeply into that. Maybe first of all, I could ask you, this is a vast subject area. What got you interested in the first place? What piqued your interest in aging that made this your lifelong interest and career?

Coleen T. Murphy: I think it’s a really interesting question. You know, I’m a scientist. I’m interested in what are some, you know, fascinating questions that we could use science to answer. And as a graduate student, I became really well trained in studying biochemistry. And at the time, I was really, became an expert in studying one particular protein and the protein it interacted with. And as you can imagine, uh, that’s not really a fun topic for everyone to talk about. I was fascinated with it, but no one else was. And so at some point, I realized that there are some really big questions. And aging is one of those where you could get interested from, you know, an epidemiological, evolutionary point of view, all kinds of different levels sociological, economic. But it’s also something that we could address scientifically. And I realized that that would be a great place to spend my time and energy is trying to understand not just what causes aging and what aging really is, but are there ways that we could slow it down? And so that’s how I got interested. It’s kind of a big idea that once I finished my PhD, I could really apply my my efforts to.

Peter Bowes: And has your attitude towards it as a subject evolved over the years? I know from a nonscientific community perspective, a lot of people begin to think about aging and their own lifespan or healthspan, as I often prefer to talk about, but the passing of the years, they notice that in midlife, in maybe their 40s and 50s, because things start changing. It might be gray hair, it might be their parents suffering some ill health or the death of their grandparents. There are life changes that affect us all that for some it’s a sort of a light bulb, isn’t it? That yes, we’re all getting old and we’re going to have to deal with it.

Coleen T. Murphy: And I’m almost feeling the opposite now that it’s becoming a reality. I kind of want to move into something else to study, but I’ve been interested since I was, you know, in my mid 30s and early 30s. And so in fact, one of the questions I addressed very early on when I started my own lab was instead of just looking at what happens late in life, really understanding that aging starts in midlife. And one of the things that would personally affect me is that even if, you know, if I could take a drug that would allow me to live to be 150, I would still at that point needed to have kids all by a certain age. Right. And so reproductive aging was one of the really big areas that I felt was neglected at the time. That was in, around 2005, 2006. And it’s interesting because in the past, you know, now, 15 years later, 20 years later, there’s a real effort to try to understand that. And I’m really gratified that some other people have picked up that that that idea that, you know, aging starts in midlife and one of the earliest consequences of reproductive aging. But then of course, immediately after that started thinking about, well, you know, my knees fall apart, things like that. But the most important thing, I think, for all of us is maintaining our cognitive function. And so that’s the other big area that my lab is interested in, because we really want to maintain our cognitive function as long as we can, regardless of like maybe our body is like won’t be the best, but like at least if our brains can work, that would give us a better quality of life.

Peter Bowes: The reproductive side of aging, which you mentioned is really interesting because I guess from an evolutionary perspective, once we have achieved reproduction that we have produced offspring, there isn’t really much reason to keep on living from a big picture evolution perspective that we have done what we were perhaps even created for, and that is to produce offspring to continue our gene pool. Is that a fair way to look at it?

Coleen T. Murphy: It is, especially when we start thinking about why do things break down, why do organisms stop putting effort into those repair mechanisms? And if we really look at the, you know, in c.elegans this, you know, the tiny nematode that we work with, which has a lot of parallels with our own bodies and how we age, I started thinking of aging as the opposite kind of really, these animals are programed to replace themselves, to reproduce. And then once that job is done, then everything after that is kind of gravy. And so instead of thinking about like looking for mutants that extend lifespan, we should be looking for things that extend how long they can reproduce, because that actually has the underlying feature, because their bodies have to stay healthy at the same time in order to do that well. And so it actually ends up extending lifespan as almost a it’s like a secondary function. It’s like a just a fringe benefit. It’s not really the main point. And that’s true for, you know, mammals as well. You know, the idea of the grandmother hypothesis is very attractive. The idea that the reason that we live so long is so that we can contribute to the fitness of our grand progeny, and there seems to be some support for that. But even C.elegans has a much longer lifespan than than its reproductive span. So that’s why I’m saying, like, lifespan is actually kind of like a, you know, it’s just extra like that extra bit after. So that’s the part. But that’s the part we really, really want to extend. So it’s important for us to understand what limits that. Why does it stop repairing itself and how can we make those mechanisms last. You know well past when they normally should the.

Peter Bowes: Idea of of living long to look after children or even grandchildren to benefit their lives is, is interesting to me because I often ask people, why are you interested in this? Why do you want to live to a great age? And almost always, the first reason is because of my children. I want to be with my children. I want to enjoy life with my children. And part and parcel of that, of course, is is doing things that will help them live good lives as well. And it’s interesting that people will say that without really thinking about it, maybe understanding some of the science that you’re alluding to. But it does seem to come. It’s almost an instinct to people that they want to continue on this earth because of their children. 

Coleen T. Murphy: That’s right.  It’s a very natural thing to want to do, and also to limit the burden that we put on our children as we grow old. Right? If we can stay healthy as long as possible, that will. That’s another way of helping our children.

Peter Bowes: So in the book, you’ve alluded to this already in terms of the wear and tear that contributes to aging. You draw the analogy with with an old car, and this is often used that we’ve all had old cars in our lives, and we see the wear and tear and the ultimate death of that vehicle. And we also know that if we maintain that vehicle and change the oil regularly in the old days before electric cars, that the car will probably survive longer. That is quite a good analogy, isn’t it, with the human body.

Coleen T. Murphy: Yeah, it’s you know, it’s a little bit cliched in the aging field, but it really is a good analogy because you really put in the effort to, you know, that that energy expenditure to repair things is exactly what our cells are doing as much as possible, and even to the point where, you know, you replace parts. Right? So we have cells that replace themselves over time. So I really do like that analogy. It’s really good. And as I mentioned in the book, you know, I did have the opportunity to go to Cuba once and you could see these old, like, these cars from the they were from the 40s. And they had been, like, continually maintained and replaced. And so they definitely weren’t even the same. They probably, maybe just even the shell of the car was the same. But like the effort that had been gone into maintaining them is very much analogous to what we’re trying to do with our own cells.

Peter Bowes: So once we have a good understanding of what aging is and why we age and some of the processes involved, why do we need to further our understanding of aging? In other words, do what a lot of people in your field are doing, and that is to try to find interventions that help us to live longer and certainly longer and healthier. That seems to be fairly obvious, but what is the impetus to really dig deep into this to try to extend healthspan.

Coleen T. Murphy: Well, one of the main things that’s been pointed out by many people in the field is that we have all these different age related diseases, and really this they, they, they’re all important to study. But if their root causes are all shared, then it makes sense to study that shared component. Right? So studying aging itself, the idea is could we slow that down. And even if we don’t live longer, you know, Jim Fries had this idea of compression of morbidity. So that means that you don’t change the lifespan of somebody, but you make them healthier so that they don’t spend a long time suffering. And then maybe, you know, you have the same life time, but only the very end. You compress the time when people are sick. And I think for most people that resonates, they may not care to live to be 100 or 150 or whatever, but they do want to spend the years that they’re on this earth as being as healthy as possible. And so that’s really the goal of much of the aging field.

Peter Bowes: And the example I give, at least in recent months, of that, of someone who really achieved that, the Queen of England, Queen Elizabeth, she lived to a great age, her mid 90s. And as we all know, she was working until just a few days before her death. That is a classic example, isn’t it?

Coleen T. Murphy: That’s right. So people who can be really functional and healthy right up until the very end, I think that’s probably the best model of how we want to maintain function with age.

Peter Bowes: Where do you stand on some of the the lingo, some of the language that is used in the longevity field? And you’re actually quite blunt about your opinions in your book. Things like reversing aging, anti-aging, which my perspective, I’m pro aging. I’m pro healthy aging because I just see it quite simply as something that’s chronological. I’m a day older than I was yesterday. My next birthday I’ll be a year older. And so it goes on. The goal for me is to age, but age in a healthy way.

Coleen T. Murphy: That’s right, I think more. I don’t want people to think that our field is promising them something that we may not be able to achieve. I think it’s good. You know, we’re trying to understand are there interventions that we can use? We can basically start, you know, giving to people that would help them slow aging. I think it’s just wrong to promise things that are just not realistic. And the reason is twofold. One, just because nobody should lie to people, and secondly, because, you know, we already have a sort of tenuous relationship with the public that is scientists, right? We many of us are trying to do the very best that we can and try to make sure that what we say is not outlandish and it’s actually realistic, and that our research, when we describe it, it doesn’t, like go way beyond what we’re trying, what we can actually achieve. Because when someone promises you something and they don’t come through, they shouldn’t have faith in you. And so that, you know, this promising of things that are never going to happen, really, destroys the public’s faith in scientists. And, you know, especially in the United States, with all the the NIH is funding most of our research. And so and taxpayers pay that. And I want the public to know that we are doing our best and we’re not lying about what we can achieve. So I just yeah, I want people to be hear the truth and not like some promise that I don’t think that we can fulfill. And it doesn’t mean that we don’t care about it. And then we’re not working our hardest to do the right thing.

Peter Bowes: So what comes to mind is this phrase we often hear; longevity escape velocity. Now maybe you can explain what that that means. But essentially it’s talking about the the speed of advances. That could actually be a tipping point in terms of aging. And to me, a lot of it does seem unrealistic and overly ambitious.

Coleen T. Murphy: Yeah, I think part of it is that we people don’t like incremental advances. They want to have like a magic pill that takes care of everything. Instead of recognizing that a lot of the breakthroughs in many fields are going to give them a tool and another tool and another tool that’s going to help address problems. For example, you know, we we don’t call statins a longevity drug, right? But they are helping people live longer. So it’s increasing our life expectancy. I think that we’ll have to see what happens with the GLP, peptides, the agonist. But if those really do help people lose weight and maintain weight and improve their cardiovascular function, in the end that should also help people improve their their lifespan, right. And healthy lifespan. And so I think the problem is people are looking for a drug that doesn’t do anything else. It only extends lifespan. But in fact, if we think about a lot of these medical advances, they are getting us there. They’re trying they’re actually attacking some of the root causes, especially the metabolic causes of our aging, and could be really helpful for a lot of people. Now, there’s also I think, there’s this idea of taking, a person who’s extremely healthy already. And making them live, I guess, forever. And so that’s different from this idea of slowing down aging and reducing age related diseases. And I think I think actually the latter is more important. Right. Like helping everybody live longer and getting reaching their maximum potential and their healthiest lifespan. I think that is actually really important. And it’s not so important to find, you know, a person who’s going to live 500 years. It’s just to me, there are different priorities.

Peter Bowes: And the suggestion sometimes that the first person to live to, I don’t know, a thousand years old perhaps has already been born. These quite wild sounding statements that you occasionally hear in terms of predictions of potential longevity. Is there any kind of science that would back up such claims?

Coleen T. Murphy: I mean, ironically, the only thing that would support any of that would be something like a are examples in C elegans, right? Where we have mutants that can live ten times as long. But, you know, I think the way to think of all the things that we find in C elegans, where we have a mutant that very, very healthy and lives twice or three times as long, when you scale that up to mammals, that gives you like a 30% boost rate. So I mean, we’ll never know, right? You and I will not be on this earth to find out the answer to this question. But my guess is no, but it’s just something exciting to say. But again, that erodes the confidence in scientists who are doing the actual science to move the field forward.

Peter Bowes: Well, let’s talk about that and maybe leave some of these potential negative connotations aside. Yes. And I was going to ask you, you’ve already in part answered this question, but I was going to ask you, and I suspect perhaps it’s the most frequent question that you hear, and that is based on your decades of research. What are the interventions that could very realistically help us just live a little bit longer and extend healthspan the number of years that we enjoy optimum health without having those chronic diseases? And to come to mind to me, is usually while you optimize your exercise, you have a balanced diet and we can debate forever what the best balanced diet is. And you get enough sleep, sleep, exercise and food come top of the list. And then the interventions, the kind of things perhaps that you’re researching.

Coleen T. Murphy: Peter, I think that’s exactly the right order of things, the right prioritization. So what you’ve just mentioned are the things that everyone can do right now to live their healthiest and probably the longest life exercise, I think is, it’s probably the strongest, actually, that one is most consistently very good. Um, and it’s one that probably people don’t appreciate enough. But we have to recognize also, not everyone is in a position to do a lot of exercise. Right? So if you’re a shift worker, if you’re, you know, so it’s really and you didn’t mention that the other way to live as long as possible is to be rich, right? Because you have the best chance of doing things like buying healthy food and having free time to exercise and having preventative health care. So those are the kinds of things that we kind of as, you know, when you have enough money, you just sort of take for granted. But actually that’s really what the things that can help everyone live longer. So if we can make them uniformly apply. So yeah, those are the things we can do. Now there are several people, you know, the scientific data all supports the idea of dietary restriction in one form or another. But if you think about it, that’s what we do to, you know, like our insects and our animals in a lab. And we don’t give them a choice. And in fact, actually if you give them a choice, they will stop doing it as soon as possible, which makes sense. Right. Um, and so the idea that a lot of people have that everybody should be dietary restricting to live their longest life, I think is both unrealistic and kind of unfair.You know, there’s very interesting statistics about who chooses to do especially extreme caloric restriction. And I think that part of the my fascination with these GLP peptides is because I think it’s getting at this root of a question of like, our brains actually control hunger. And so I think that those levels of these peptides are different in everyone. And so some people probably feel hungry all the time and other people don’t just based on their chemistry. And so I think it’s interesting to look at who chooses to dietary restrict themselves and who really can’t. And there’s yeah. And it’s not really a moral judgment. I think we have to get away from that. I think there’s like definitely chemistry in our brains and our bodies that affects how we feel towards food. And it’s not that easy to caloric restrict for most people. And so I think that part of the reason it’s important to understand the science of caloric restriction is so that we can figure out, okay, is there something we can do that would mimic that state and help us be healthy, but wouldn’t cause us to lose out on? One of the greatest joys in life is to, you know, eat a good meal. Right? And so I think, moving us forward scientifically will be understanding all those pathways. So that we don’t have to miss out on things that are just like part of having a high quality life.

Peter Bowes: I think as far as caloric restriction is concerned, people are a lot of people are just simply confused by the extremes that they hear about. So you might hear about certain people who will frequently go without food or water only diet for several days, which is very, very extreme. At the least extreme, you could say, well, maybe you’re going to calorie restrict by just not having a dessert on three days a week. That for some people, is limiting calories by just paring back a little bit every day. And I often use the word moderation. That could be one of the best interventions. And the issue there maybe the challenge there from a societal perspective, I wonder what you think about this is, is education education to show people that, yes, you might be you can call it caloric restriction. Other people might just call it cutting back on a few meals, or just eating less, or having half a plate instead of a full plate a few times a week.

Coleen T. Murphy: But again, yeah, that’s all true. But again, none of that is really like the cutting edge of aging research, right? It’s just sort of what we kind of known for a long time. That’s why I’m I’m actually a little bored by all the dietary restriction stuff other than trying to understand, like what are the mechanisms and what are the what are the, you know, the real genetic components and how can we manipulate those? Because from a scientific perspective, that’s actually really interesting. But from a societal point, like all these discussions about what we should and shouldn’t eat, and it changes all the time too, right? If you notice, like there’s these huge trends and, and so in nutrition science. And then when you find out some of the backing for that is always a little bit disturbing. So I want to stick to the the molecules. And the hope as I said, is, you know, I hope that we’ll get to a point where, we can separate the idea of like living longer and then having to, like, have a terrible life because I frankly, I really think that a lot of the dietary restrictions, like we do it to c.elegans. We we see they have a better, longer lifespan. I just think that’s not really a great way to live. And so I’m not focused on that particular thing. I think there’s a lot of other more interesting ways to live longer.

Peter Bowes: Okay. Well let’s talk about them. What do you think are the the more interesting ways to live longer? Yeah.

Coleen T. Murphy: Well, you know, understanding the genetics. Right. So we have this great, model system. And really, you know, when I got into the field, part of the reason was because I had read about and then heard Cynthia Kenyon talk about her lab’s work. So that’s where I did my postdoc at UCSF. And she had discovered there are these mutant c. Elegans. So, like, it has a change in a single nucleotide and a single gene in this worm, and it lives twice as long. And it’s super healthy, right? It’s not like on its deathbed for a long time. It really stretches out the healthy part of lifespan. And we found that those worms actually maintain their oocytes longer so they have a longer reproductive span. And we know the mechanisms now why that happens. And they maintain their neurons longer so they can we figured out how to do learning and memory assays in these animals. So they actually maintain their cognitive function longer. And so those are and so understanding how those animals do that and uncovering all the genetics gives us new possibly pharmaceutical targets. Right. Because then we can say, okay, I see that those long lived, you know, long remembering worms turn up this protein. What if I found a drug that could do the same thing, right. So that would be great. And so that’s why it’s really important for us to do the not just stop at, oh, like, okay, well I’ll just stop eating and live longer that like instead if we can actually figure out, like, what is the thing that we want to do better and can we find a drug that does that well and makes and not bad. That would be great. Right. And so I think, you know, there’s a whole biotech industry that’s just starting to take off. And that’s like, you know, the end of my book is mostly about that and how we’re on the verge. I think there’s really a lot of exciting science that’s gone from the lab to now, these biotech startups and other things that we’re just on the verge of it. So that’s why I kind of want the your audience to know is that we’re not going to we we’re not going to we shouldn’t say, oh, we found out everything. We’re. We’re done. We know everything about longevity. We actually are learning a lot. But now we’re at a stage where those things are being translated, I think, into possible interventions, and that is really exciting. And so what I hope the readers get out of this is some information about what those interventions might be like, what’s the molecular basis for it. And and sort of, you know, what to look for, who might who might actually crack this. That’s really exciting to me.

Peter Bowes: And just remind us, you mentioned C elegans, this little tiny nematode worms several times which are used, have been used for a long time extensively in this area of research. Why are they such a good model.

Coleen T. Murphy: Ah okay. So these I should have introduced them better myself. So you know they’re tiny little animal. They only they look like a, like if you held up the plate of them they look like lint. So they’re they’re transparent. We look through them. Can see them without a microscope. The reason they’re so great is because we can manipulate every single one of them, but we can. They live for only three weeks, and during that time, if you looked at them under the microscope, anyone would be able to tell me, oh, that one looks like a young one, and this one looks old, because they actually they start to get wrinkled and fat and they start stop moving well, right. So they really are reminiscent of the kind of aging changes that we see. And like I said, this mutant, the insulin receptor mutant daf-2 that Cynthia Kenyon first identified, that lives twice as long and it’s super healthy and does everything. So that is a great, you know, it’s a great tool. And so people have also done great studies, for example, in Drosophila. So those two animals, the C elegans and Drosophila. Yeah, the fruit fly. Those have given us so much information about how to live longer and better lives. And I think that’s underappreciated in general because like often people will skip straight to the mammalian studies, the mouse studies and things, which is important, right? We take our stuff in worms and we go look at what happens in a mouse before we move on. But it’s really easy to find important things in these model systems. And so that’s why we’re so excited about it. And I want people to know that that’s how much much of the aging field, many of the genes that we study, they are really well characterized in those animals. 

Peter Bowes: I think it’s important to explain that because a lot of people will dismiss longevity science when they discover that it is, as they might put it, only animals or we’re all animals, but it was done in rodents or fruit flies or or tiny worms. And that, as you’ve explained, there is a there’s a process here that that’s where it starts. And and clearly, especially with drug interventions, there has ultimately to be human trials.

Coleen T. Murphy: That’s right. And so the other thing you can do in these small systems is, is figure out what’s safe. You know, if we did a drug screen, for example, in C elegans, we found out that some drug that we were really interested in for the brain ended up killing all of them. We would never move forward with them. Right. So it’s just such an easy tool to use, but so powerful because you can do so much so fast. So that we hope that by the time we get to the point of doing a collaboration with, like our colleagues who work with mice, that will have done something that where we really understand it, because it’s also very expensive to do these studies in higher organisms. And so we don’t want to waste a lot of time and money and animals studying something that’s not important. So that’s, you know, these these invertebrate systems are fantastic for all of those reasons.

Peter Bowes: And once we get to the point where there are more and more nutraceutical, pharmaceutical interventions based on decades of solid science, and we see, as I say, more and more of them on the market, then comes the dilemma for people, doesn’t it, of, well, what’s best for me? And how can I choose the best intervention? Yes, based on science that is going to help me achieve a greater, healthier age. And that is I mean, that’s already a real reality now, isn’t it, for so many people in terms of how to parse apart all the science and figure out what is the most positive for them?

Coleen T. Murphy: That’s absolutely. And in fact, it’s made a little bit more complicated because we also have to take it face value. So say you order some nutraceutical, you have to take at face value what’s going to be in that bottle. Because right now we nutraceuticals are treated differently from drugs, and the FDA is not going through the process of approving them. And so one of the really great efforts that’s happening right now is being organized by Nir Barzilai at Einstein. Is this T.A.M.E trial. So that’s a trial when we’ve known that metformin is beneficial for years and years. Right. And so this is an example trial of trying to figure out whether if you did a large clinical trial, could you actually say this drug should be helpful for longevity. And they’re doing that by a variety of metrics, right. Like health metrics, including looking at what changes in the blood. And the idea here is that if you since that’s a pilot program, could you then convince the FDA that we should be doing trials to like check efficacy? Right. And I think that’s really important to do because right now, you know, you have to trust, like what’s being sold. I think that’s a little scary. And I was at a meeting in September where someone had taken like, just like various I forget which drug it was. And they and they did mass spec on it and only one of the like eight that they bought had the drug that was supposed to be in it. And so I think that’s a big concern. So that’s even separate from making the decision of what I should take. So say you, you know, what’s in the bottle is true. And the FDA said it was like something, you know, also companies are having to make the hard choice of how do you test something for efficacy because they want to get something that’s real, too, not just because, you know, down the line, it’s important for these companies to survive and make good choices. And so. Several of them are doing smart things by testing not for longevity, but for age related diseases. Right. And so that’s pretty smart because if you can, you know, find a real disease that you can track, then you can, you know, subject that to an FDA trial. And so I think those kinds of approaches are really important for moving the field from like this idea and, you know, nutraceutical like maybe it works, maybe it doesn’t to something that’s really a trusted drug that that you could be prescribed by your doctor.

Peter Bowes: I think you’ve highlighted a really important issue and problem. And tragically, sadly, we live in this unscrupulous world these days where you really find it difficult to believe anything, and especially that you’re reading on the internet, and the purity of these compounds that people are potentially buying is such a such a vitally important issue. And people can often be easily led, I guess, when something is being offered to them at a cheaper price, and they assume it is the same thing as they’ve been paying a little bit more for and likely to go down the cheaper road. And it may not be what they think it is in that little bottle.

Coleen T. Murphy: That’s right. And you know, and of course how. And then you also like to get into the whole psychosomatic thing of like is something really like, are you just, you know, having some sort of placebo effect. You’re taking something. So I think we have to have some real metrics to be able to tell a patient, yes, you’re actually, you know, slowing down your aging. And there’s some diagnostics that are getting there. You know, whether they’re quite there yet or I’m not sure, but but that’s, you know, one of the efforts of the field as well is to do things like these, you know, blood diagnostic clocks, like the aging clock kind of methylation DNA markers and try to say, well, can we actually measure your aging rate, measure your age, and then how that changes when you take an intervention. Right. So I think once we get those working really well, that could be a very effective tool to be able to help people assess how fast they’re aging and whether the thing that they’re taking is actually doing something or not.

Peter Bowes: And that’s another area of confusion sometimes in terms of biological aging, chronological aging. You’re talking about attempting to assess our biological age, which in itself is a complicated equation. And there are lots of companies out there with different metrics and different ways of calculating that. We need to, I think, settle on a way that is, is broadly agreed as, as the way to determine someone’s biological age. Otherwise you’re just going to perpetrate more confusion.

Coleen T. Murphy: That’s right. And like I said, I think that there are real efforts is I don’t you know, the scientists who are working on this are not trying to pull a fast one. They’re actually really trying to develop a clock clocks that they really do find reproducible and accessible. So like, I think that we’re going to get there because there are a lot of efforts being made to that, to that to address that point.

Peter Bowes: You we’ve talked a little bit about exercise and how crucially important I think I would put exercise at the number one of my my list of things that I need to achieve every day. Will we and you address this in the book, do you think we’ll get to a point where there is exercise in a pill?

Coleen T. Murphy: Well, I do think we already have a few of those drugs that do help boost muscle function. And again, you know, there’s a perspective from people like you and I who are, you know, pretty healthy sitting here. There are people who are never going to be able to exercise for one reason or another. And so finding drugs that could help them as well, that’s actually one of my favorite themes lately in the aging field is this idea that, okay, not worrying about the guy who’s just trying to, like, maximize his life forever, but instead focusing on people who, you know, if you have some sort of degenerative muscle problem, this might be helpful. Or my favorite one recently is looking at there’s the idea that for senolytic drugs, this might help patients. So people who had childhood cancers because they have a lot of problems come midlife. And so if some of these anti-aging kind of therapeutics that we’re developing could help any people in that situation, it would be fantastic. So I think we can’t think of all, you know, longevity and aging research as a fundamentally selfish endeavor. It actually could help a lot more people than we are initially realizing.

Peter Bowes: And there’s a lot of really fascinating research going on at the moment into mitochondrial health and essentially the the energy centers of our bodies. The payoff from good strength there is good physical strength, good muscular strength that translates into perhaps not falling down when you’re older.

Coleen T. Murphy: That’s right.

Peter Bowes: It prevents frailty. There’s a long sequence of benefits there. And I know you’ve looked into this as well in terms of the work that’s going on, trying to understand mitochondria and how to to boost our mitochondrial health.

Coleen T. Murphy: Yeah, it’s funny because in my own lab I sworn to never work on mitochondria. And then at some point I ended up studying and figuring out, you know, we were looking at reproductive aging. And we discovered that Urolithin A actually really helps them maintain their oocyte function longer because they’re oocytes. It turns out their mitochondria are like basically they’re one of the main things that fall apart. And yeah, mitochondria, it’s undeniable. They are super crucial. And helping them maintain function not only helps with muscles, but it turns out neurons as well. And so, yeah, mitochondrial health is super important. And there are several drugs that that could be helpful with that as well. And those some of those are actually being marketed as well.

Peter Bowes: Let me ask you a more personal question. As you age, and we kind of touched on this already, our attitudes change or the ideas that we’ve had maybe are set aside for for newer ideas about aging and how we as an individual want to approach it, what we can do to pursue our own healthy longevity. Have your attitudes in that respect changed as a result of some of the research that you’ve done?

Coleen T. Murphy: Ah, so my research, um.

Peter Bowes: Oh, maybe not your research, maybe your life experiences.

Coleen T. Murphy: I don’t know.

Coleen T. Murphy: Like I said, I’m, I don’t know. As it becomes real, I just kind of want to step away and start. Just focus on the curiosity driven problems that. No, I have like almost two minds, like we like in my own lab really, really started to focus almost exclusively on maintaining cognitive function. So doing drug screens for that, because I feel like this could be a really good path forward regardless of. And there may be even like side effects that are beneficial as well. So for example, we just had a paper with our collaborator Saul Villeda. So Saul’s lab is focused. He’s actually one of the people who’s done the parabiosis work, you know, the stitching of the two animals together and finding out that there’s factors in the blood that are shared. So that’s what he was already famous for. So we had discovered in C elegans there is a particular protein that if we make more of it and make it more active just in one neuron, we can turn that on and turn that on in one neuron of old worms, and it completely rescues their memory, of course. So you’re like, oh, that’s nice, that’s worms. But then we convince Saul to help us, and he and Gregor Bieri in his lab, they injected that same mutated version of the protein. So worms and mammals have the identical protein. And we made they made the same mutation and injected it into the hippocampus of two year old mice. So two year old mice are about 70, effectively like a 75 to 80 year old person. Okay. And these mice already were experiencing some cognitive decline. So they injected into the brains and then let them recover and then subjected them to some behavioral assays. And what they found was that these mice have great memory. So just this one protein, just activating it in the right place in old animals completely rescued their memory. And also they started behaving in a younger way, which I couldn’t. They quantified and I can’t explain how that works. So,now we’re really interested in the idea of could we find a drug that mimics that effect? Right. So that would be a that’s an example of what we can do, that where we go from worms to higher organisms. And so that’s the part that I’m really interested in, because I think maintaining cognitive function is probably my number one priority as far as the aging field goes. Me personally, no, I, I’d love to be able to get back to sprinting. Right. But that’s like that’s a different thing altogether that that probably doesn’t have anything to do with my labs research.

Peter Bowes: Right. Just to delve a little bit into that research that you mentioned. So how do you assess a mouse in terms of its memory ability, and is there a definition of what a mouse is doing that shows it’s behaving in a younger way?

Coleen T. Murphy: Yeah. So for the for the first part, the memory. So that’s actually a really well established field. And lots of other great neuroscientists have worked on that for a long time. In Saul’s lab in particular, what they were using were two different tests, one called the Novel Object Recognition Test. So that’s when mice are in a cage and you put an object in it and let them get used to it, and then like a day later, they’ll ignore that one. But if you put another object in there, they’ll pay more attention to that new thing. Okay. So that means that they remember the old one and they and so basically you can track how much time they spend with that new object. So that’s one test. And then there’s the radial arm water maze. So that’s where you have a platform where the mice can swim to get out. But they have to remember where that platform is. And so you can and they learn to do that over time. So in that same assay you can measure learning short term memory and then long term memory. And you can measure the number of errors that they make. And so the you know the mice where we put the protein in it actually they made fewer errors and they had much better long term memory. Okay. Now as far as the health metric, that was kind of cute because I didn’t know about this before Saul called me and told me that he observed this and that was that. He was. If you look at the mice in their cages, apparently young mice sort of make these nests and they take care of them with their bedding. And then when they get old, you know, like all of us stop caring around our environment. And they stopped doing that. They stopped caring about their environment, stop making these little nests. And so you can have this non-parametric. You can actually, like, look at them and give them a score from good to bad. And the mice with this rescued protein actually it made their made them take care of their nests again. So I don’t know the molecular mechanism behind that at all. It was just an observation. But it was a significant difference. And so that made me that made me very happy because it also suggests that this modification we made, because you can go two ways, right? You can have something, what is it? Flowers for Algernon. Right. You like, you can have an improvement in your brain. But then there’s something else that would do negatively. Right? And that’s really what we don’t want to do. And so what we want to do is something where we maintain our brain. But also, you know, it would be nice to also have some like health effect as well. That’s positive.

Peter Bowes: Really interesting. Fascinating. Let me ask you, in closing, a sort of big picture question. And that is is life in this world, this earth that we live on worth living for a long time? And I’m thinking of those geopolitical issues that we all face, those climate issues that we’re facing, and they’re posing a real challenge to mankind at the moment. Is this going to be a world that we want to live in for a long time?

Coleen T. Murphy: And that’s, you know, Peter, that’s the point I make at the very end of my book, and I appreciate you bringing it up. We really need to keep in mind that if we want to live so long, there better be an earth left for us to live on and in all possible ways, right? Like we need to pay more attention to our climate. That’s there’s real urgency there, and we need to pay attention to other human beings that we’re living with on this earth. And so if we don’t do those two things, then it doesn’t matter if we invent a pill tomorrow to live 500 years, right? So we really need to pay attention to all those things and not just focus on this one area. So, you know, as a scientist, we do what we can. But it’s up to all of us to try to make this place a world worth living in.

Peter Bowes: I couldn’t agree with you more. Colene Murphy a fascinating conversation. We’ve just really skirted around the surface of the very deep dive that you do in this book. And as I mentioned at the beginning, looking back over decades of really interesting research, thank you very much indeed.

Coleen T. Murphy: And thank you for having me, Peter.

Peter Bowes: My pleasure. Coleen Murphy’s book is How We Age: The Science of Longevity. There’s a link to it in the show notes for this episode, along with a transcript of this conversation. This has been a Healthspan Media production. We’ll be back with another episode very soon. In the meantime, thanks so much for listening.

The Live Long and Master Aging (LLAMA) podcast, a HealthSpan Media LLC production, shares ideas but does not offer medical advice. If you have health concerns of any kind, or you are considering adopting a new diet or exercise regime, you should consult your doctor.


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