Are scientists being honest about aging research?

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. 

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' while Prof. Murphy argues that without taking care of our planet and its inhabitants, the quest for longevity loses much of its significance.

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

Coleen T. Murphy: 0:21

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. So that you know this promising of things that are never going to happen really destroys the public's faith in scientists.

Peter Bowes: 0:53

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 ame 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: 1:34

Thank you for having me, peter.

Peter Bowes: 1:36

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 lots of different definitions from researchers and scientists, but what is your view on what aging is?

Coleen T. Murphy: 1:59

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 ourselves 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: 2:46

Well, we're gonna 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: 3:03

I think it's a really interesting question.

Coleen T. Murphy: 3:06

You know I'm a scientist.

Coleen T. Murphy: 3:07

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, that's not really a fun topic for everyone to talk about.

Coleen T. Murphy: 3:31

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 and has your attitude towards it as a subject evolved over the years?

Peter Bowes: 4:19

I know, from a non-scientific community perspective, a lot of people begin to think about aging and their own lifespan or health span 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: 4:50

And I'm almost feeling the opposite now that it's becoming a reality.

Coleen T. Murphy: 4:54

I kind of want to move into something else, to study but I've been interested in 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.

Coleen T. Murphy: 5:14

And one of the things that would personally affect me is that, even if I could take a drug that would allow me to live to be 150, I would still at that point, need it to have kids all by a certain age, and so reproductive aging was one of the really big areas that I felt was neglected.

Coleen T. Murphy: 5:31

At the time that was around 2005, 2006. And it's interesting because in the past, 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 idea that aging starts in midlife and one of the earliest consequences of reproductive aging. But then, of course, immediately after that, start 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 bodies won't be the best, but at least if our brains can work, that would give us a better quality of life.

Peter Bowes: 6:16

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: 6:45

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 CL against 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 programmed 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 a mutant that extends 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 just a fringe benefit. It's not really the main point, and that's true, for you know mammals as well.

Coleen T. Murphy: 7:39

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 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 it. 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?

Peter Bowes: 8:16

The idea of living long to look after children, or even grandchildren, to benefit their lives 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 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: 8:56

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: 9:08

So in the book you've told you've alluded to this already in terms of the wear and tear that contributes to aging you draw the analogy 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 or 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: 9:38

Yeah, 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 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: 10:26

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? 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 health span?

Coleen T. Murphy: 10:57

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 they're all important to study. But if their root cause is 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? Jim Fries had this idea of compression of morbidity, so that means that you don't change the life span of somebody, but you make them healthier so that they don't spend a long time suffering, and then maybe you had the same lifetime, 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 to 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: 11:50

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 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: 12:05

That's right. So people who can be really functional, healthy, right up into the variant. I think that's probably the best model of how we want to maintain function with age.

Peter Bowes: 12:14

Where do you stand on some of 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. Look things like reversing aging, anti-aging, which, from 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 year older, and so it goes on. The goal for me is to age, but age in a healthy way.

Coleen T. Murphy: 12:45

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.

Coleen T. Murphy: 13:05

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.

Coleen T. Murphy: 13:20

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 we can fulfill it and 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: 14:16

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: 14:39

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 an 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 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.

Coleen T. Murphy: 15:32

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 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 gonna live 500 years. It's just to me they're different priorities.

Peter Bowes: 16:52

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: 17:11

I mean, ironically, the only thing that would support any of that would be something like our examples in C elegans, right, when we have mutants that can live 10 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 it's very healthy and lives twice or three times as long, when you scale that up to mammals, that gives you like a 30% boost, right? So I 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 some of the erodes the confidence in scientists who are doing the actual science to move the field forward.

Peter Bowes: 17:51

Well, let's talk about that and maybe leave some of these potentially negative connotations aside.

Peter Bowes: 17:56

Yes, and I was going to ask and you've already in part answered this question, but I was going to ask in 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 health span, 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: 18:40

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 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 know, so it's really and you didn't mention that the other way to live the longest 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 preventive 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.

Coleen T. Murphy: 19:40

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 as soon as possible, which makes sense, right. And so the idea that a lot of people have, that everybody should be dietary restriction 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 extra, especially extreme caloric restriction, and I think that part of these, that my fascination with these DLP 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 like they're not. They 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.

Coleen T. Murphy: 20:51

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 because it's a very important thing, and so I think that's why we're trying 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: 21:31

And so I'm 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 pairing back a little bit every day, and so I think that's why we can 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 if you think about this is education, education to show people that you 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: 22:26

But again, none of that is really like the cutting edge of aging research, right.

Coleen T. Murphy: 22:30

It's just sort of what we kind of known for a long time.

Coleen T. Murphy: 22:33

That's why I'm actually a little bored by all the dietary restrictions and stuff other than trying to understand, like, what are the mechanisms and what are the you know, the real genetic components and how can we manipulate those.

Coleen T. Murphy: 22:44

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 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 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 have, like we do it to C elegans, we see they have a better, like a longer lifespan. I just think that's not really 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: 23:34

Okay, well, let's talk about them. What do you think are the more interesting ways to live longer? Yeah, well.

Coleen T. Murphy: 23:39

I, you know, understand the genetics, right. So we have this great model system and really, you know, when I got into the field, the part of the reason was because I had read about and then heard Cynthia Kenning give her 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've 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 undercovering 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 it all, like okay, well, just stop eating and live longer. That like instead, if we could 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 trying to take off and that's like you know.

Coleen T. Murphy: 25:10

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 has gone from the lab to now these biotech startups and other things that were just on the verge of it. So that's what I kind of want the audience to know is that we're not going to, we're not going to. We shouldn't say, oh, we found out everything, we're done, we know everything about longevity. We actually are learning a lot, but now we're on 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 I'm sort of getting you know what to look for. Who might, who might actually crack this? That's really exciting to me.

Peter Bowes: 25:56

And just remind, as 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: 26:09

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 on 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 while 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 start 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, daf2, 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 sea elegans and.

Coleen T. Murphy: 27:08

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 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 of the aging field. Many of the genes that we study they are really well characterizing those animals.

Peter Bowes: 27:42

Yeah, and 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 tiny worms, and that, as you've explained, there is a process here, that that's where it starts and clearly, especially with drug interventions, that has ultimately to be human trials.

Coleen T. Murphy: 28:06

That's right, and so the other thing you can do in these small systems is figure out what's safe. You know, if we did a drug screen, for example, in sea elegans, we found out that some drug that we're really interested in for the brain ended up killing all of them. We would never move forward with them, right? So it's, it's just such an easy, easy tool to use, but so powerful because you can do so much so fast. So we hope that by the time we get to the point of doing a collaboration with, like our colleagues who work with mice, that we'll have done something that where we really understand it because it's also very expensive to do these studies and in higher organisms, and so we don't want to waste a lot of time and money on 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: 28:56

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, it is going to help me achieve a greater, healthier age, and that is, I mean, that's already a reality now, isn't it for so many people in terms of how to pass apart all the science and figure out what is the most positive for them?

Coleen T. Murphy: 29:30

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 it face value what's going to be in that bottle? Because right now 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 Neera Bartzellay at Einstein is this TAME trial. So that's a trial.

Coleen T. Murphy: 30:00

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 did mass spec on it, and only one of the like eighth 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.

Coleen T. Murphy: 31:01

So, say you, you know what's in the bottle was 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 trust 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 no nutritional like, maybe it works, maybe it doesn't. It's something that's really a trusted drug that you could be prescribed by your doctor.

Peter Bowes: 31:50

I think you've highlighted a really important issue and problem and tragically, suddenly we live in this unscrupulous world these days, why 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 lead, 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, unlikely to go to cheaper road and it may not be what they think it is in that little bottle that's right and you know, and, of course, how.

Coleen T. Murphy: 32:30

And then you also like 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 some? 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 are getting there. You know whether they're quite there yet and not sure, but but that's, you know, one of the efforts of the field as well as to do things like these. You know blood diagnostic clocks, like the I'm aging clock kind of methylation DNA marks, 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: 33:20

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 in 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.

Coleen T. Murphy: 33:47

Otherwise, you just going to Puppet a more confusion that's right and, like I said, I think that there are real efforts is, I don't you know, the scientists are working this. You're not trying to pull a fast one, actually really trying to develop a clock, clock 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: 34:11

You. We've talked a little bit about exercise and how crucially important I think. I will put exercise that 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: 34:26

Well, I do think we already have a few of those drugs that do help boost muscle function.

Coleen T. Murphy: 34:34

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 Satellitic drugs, this might help patients, so people who had childhood cancers, because they have a lot of problems come in life, 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, aging research as a fundamentally selfish endeavor. It actually could help a lot more people than we are initially realizing.

Peter Bowes: 35:34

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 that's right, 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 boost our mitochondrial health.

Coleen T. Murphy: 36:01

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 figure it. You know we were looking at reproductive aging and we discovered that your life in a actually really helps them maintain their oversight, function longer, because they're their OSI turns out there. Mitochondria, like basically, they're one of the main things that fall apart and, yeah, mitochondria it's, it's Undeniable, they're 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 are actually being marketed as well.

Peter Bowes: 36:48

Let me ask you a more personal question. As you age and kind of touched on this already our attitudes change, or the ideas that we've had maybe 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: 37:14

Awesome, my research.

Peter Bowes: 37:16

Or maybe not your research, maybe your life experiences.

Coleen T. Murphy: 37:19

I don't know. Like I said, I don't know as it becomes real, I just kind of a 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 collaborators, all the data. So a saws lab is Focus.

Coleen T. Murphy: 37:55

He's actually when people is on the pair of biosis work, you know the stitching of the two animals together and finding out that there's factors in the blood they're sharing. 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 out in turn that on in one neuron of old worms and it completely rescues their memory. Of course you're like, oh, that's nice, that's worms. But then we convinced saw to help us, and he and Greg beer 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 same mutation and injected into the hippocampus of two year old mice.

Coleen T. Murphy: 38:45

So two year old mice are about Seventy, effectively like a seventy five to eighty year old person, 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, and old animals completely rescued their memory and also they started behaving in a younger way, which I couldn't be 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 an example of what we can do, that where we go from worms to higher organisms, and so that's the part I'm really interested in, because I think maintain cognitive Functions probably my number one priority as far as the aging field goes. Me personally, know, I love to be able to get back to sprinting, right, but that's like that's a different thing altogether.

Coleen T. Murphy: 39:48

That probably doesn't have anything to do with my lab research.

Peter Bowes: 39:52

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 its behaving in a younger way?

Coleen T. Murphy: 40:05

Yeah, so for the, for the first part, the memory. So that's actually really well established field and lots of other great neuroscientists have worked on that for a long time. In Sal's lab in particular, what they were using were two different Test one called the novel object recognition test. That's when my son a cage, and you put an object in it and let them get used to it and then, like a day later, 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 radio arm water maze. So that's where you have a platform where the mice can swim to get out. But they have to remember when that platform is, and so you can, and they learn to do that over time. So in that same asset 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.

Coleen T. Murphy: 41:12

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 stop doing that. They stop 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.

Coleen T. Murphy: 41:39

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 you made because you can go to age, right, you can have something what is a flower for Algeron, right, you like, you can have an improvement in your brain. But then there's something else they 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 don't be nice to also have some like health effect as well.

Peter Bowes: 42:21

That's positive really interesting, fascinating. Let me ask you in closing a 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: 42:49

and that's you know, peter, that's the point I make at the very end of my book. I appreciate you bring it up. We really need to keep in mind that if we want to live so long, there's better be an earth left for us to live on and all possible ways right, like we need to pay more attention to our climate. That's real. 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 who 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: 43:31

Couldn't agree with you more. Coleen Murphy is 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.

Coleen T. Murphy: 43:44

Thank you very much indeed and thank you for having me here.

Peter Bowes: 43:47

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 health span media production. We'll be back with another episode very soon. In the meantime, thank you so much for listening.