BY PETER BOWES | LOS ANGELES | MARCH 31, 2021 | 0702 PT

Cracking the code behind aging has long since fascinated, frustrated and captivated scientists.  In our quest to live longer and better, a desire to fully understand the mechanisms that explain how and why we grow old, has been central to longevity research. In recent years some significant progress has been made. A clearer picture is emerging of the changes that occur, at a cellular level, that could dictate how our bodies respond to the passing years. In this episode of the LLAMA podcast, Prof. David Walker, a researcher at the University of California, Los Angeles (UCLA), discusses his work with tiny worms and fruit flies, and explains the significance of myriad age-related issues, such as dysfunctional mitochondria, leaky intestines and inflammation. 

Recorded: March 2, 2021 | Read a transcript 

Connect with Prof. Walker:   UCLA bio/publications | UCLA Microbiome Center | LinkedIn | JUVICELL

Disclosure: Prof. Walker is a member of the scientific board of JUVICELL, a sponsor of this LLAMA podcast episode. 

Topics covered in this interview include:

• Dr. Walker’s academic journey from Belfast to Manchester and Los Angeles. 
• Inspiration through  Jonathan Weiner’s Time, Love Memory – a biography of Seymour Benzer, the biologist renowned for his study of genetics through experiments with fruit fly genes.  
• Working with nematode worms and fruit flies.  
• Aging – a great scientific mystery.  How our understanding of what is driving aging, at a cellular level, has evolved. 
• Developing novel ways, using genes, to prevent age- related health decline.  
• Changing awareness of aging as we grow older.
• Accumulation of dysfunctional mitochondria and how it appears to be an important cellular hallmark of aging. 
• The importance of autophagy for maintaining cellular health.
• Why do we age at different rates?  
• The pathophysiology of aging: How do age-related changes that affect organ function, relate to the health and viability of the aging organism?    
• Leaky intestines in fruit flies and humans . 
• Inflammation and the link to age-onset diseases
• Gut bacteria and relevance to various diseases and health interventions. 
• Diet and variability of our gut microbiome.
• High/low  protein diets and the aging gut, based on fruit fly studies.  
• Does eating less protein enhance longevity? 
• Making better informed decisions about diet and dietary supplementation. 
• Practicing ”  common sense” lifestyle goals. 
• Exercise and everyday diet    to counter the effects of aging. 
• Memory loss  as we age and a better understanding of the mechanisms involved based on studies with fruit flies. 
• Lifestyles focussed on living life to the full.

“This is it, this is our life and we have to make it count.”

Prof. David Walker

The Live Long and Master Aging podcast 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.

TRANSCRIPT

David Walker: [00:00:02] I’m a big believer in ‘this is it, this is our life’` and we have to make it count. And you know what makes us happy in our everyday life and in the longer term, it is really important.

Peter Bowes: [00:00:22] Hello again and welcome to the Live Long and Master Aging podcast. This is where we explore the science and stories behind human longevity.

SPONSOR MESSAGE: [00:00:30] This episode is brought to you in association with JUVICELL, the all-in-one longevity supplement that contains 10 key ingredients shown to have a positive impact on healthspan as validated by scientific studies. To find out more, visit JUVICELL.com. That’s JUVICELL.com. 

Peter Bowes: [00:00:52] Today, we’re going to dive into some of the science and research as it happens, research going on here in Los Angeles into the biological mechanisms of aging, which the better we understand, the more likely we are able to develop interventions and preventative strategies to mitigate the downsides of getting old, the cognitive and physical decline that comes with aging. My guest is Dr. David Walker, professor in the Department of Integrative Biology and Physiology at UCLA, the University of California, Los Angeles. Dr. Walker, welcome to the Live Long and Master Aging podcast.

David Walker: [00:01:28] Great to be here and wonderful to meet you, and I’m looking forward to this discussion.

Peter Bowes: [00:01:33] Me, too. We are, as I mentioned, in the same city, we’re doing this remotely, which is a little bit frustrating. It’s necessary because the times that we’re going through, how has the pandemic, the past year, how has it affected you and your work?

David Walker: [00:01:45] You know that, of course, there have been a lot of challenges, you know, with the lab was shut down from mid-March until June and then we slowly ramped up and where, you know, we’re making progress. But, you know, it’s been lots of challenges. But I start to see the light at the end of the tunnel. I start to, you know, regain some optimism. And I think things are starting to go finally in the right direction. And hopefully we can put a lot of this behind us.

Peter Bowes: [00:02:16] Yeah, I totally agree with you. So let’s talk about your background initially and actually before we delve into that, just for full disclosure, this podcast, as we’ve just mentioned, is supported by JUVICELL. You’re a part of the scientific advisory board for JUVICELL. Aren’t you?

David Walker: [00:02:32] Yeah, that’s right, that’s relatively recent happening. It’s something that’s just happened within the last few months, but something I’m excited to be involved in.

Peter Bowes: [00:02:43] Ok, so let’s talk about your work, and I know you’ve been on quite a journey in terms of your education and at least one place that you’ve studied in leapt out at me, Manchester in North West England, which is a city that I know quite well.

David Walker: [00:02:56] Oh, interesting, interesting, yeah, so even before I give the, you know, short but full history, I grew up in Belfast in the North of Ireland, in the you know, the 80s really, and did my undergrad degree at Queen’s University, Belfast undergrad degree in genetics and really just became fascinated by my genetics and how we can both better understand, you know, mechanisms of disease and even behaviour and many different things. And then after completing that degree, yeah, I was interested to a) study for a PhD and b), get out of Northern Ireland at that time. And I was and remain a big fan of Manchester United. And that was not that was part of it wasn’t the only reason. But I looked around and got accepted in a few programs, mainly in Scotland and England and Manchester United. The Manchester music scene was was really, really buzzing at that time. And also Manchester has a couple of great universities and it’s a great, great university town. It’s a very fairly diverse, you know, English city, probably second only to London. Right. I did a master’s degree and also my Ph.D. there.

Peter Bowes: [00:04:25] So then you eventually move to California.

David Walker: [00:04:27] Yep, so maybe four or five years of gray skies and rain and, you know, Manchester United had just won the treble, so I don’t know what was left to do after that. So.

Peter Bowes: [00:04:41] And the weather gets to everyone eventually.

David Walker: [00:04:43] Eventually, eventually, you know, I was always going to do a postdoc and it coincided, I read a book called Time, Love and Memory, which it wasn’t an autobiography, but it was a biography of Seymour Benzer, who was really one of the giants of biology of the last, you know, 60, 70 years. And he had just started getting interested in ageing research. So my own Ph.D. work was also on aging, and I studied aging in a tiny microscopic nematode worm, which is a great genetic model to this day. And Seymour Benzer had started getting interested in studying aging in a different invertebrate model, the fruit fly Drosophila. And like I say, I recently read just out of interest, not I didn’t think I would have anything to do impact my career in any way, but a great biography of Benzer, Time, Love and Memory. And he was based at Caltech, which is in Pasadena, you know, still technically in the same city that we’re both in today. And, you know, of course, I’d heard of, you know, Stanford and MIT and Harvard, you know, and all these other great American universities. But actually, for whatever reason, Caltech. I knew of Richard Feynman, of course, but for whatever reason, I wasn’t quite as familiar. I couldn’t even I could look it up where exactly it was on the map. But I became and I wrote to Seymour and the rest is history, I guess. So I ended up going on to do my Ph.D. postdoc postdoc sorry, in the early 2000s in Caltech.

Peter Bowes: [00:06:31] And you mentioned nematode worms and fruit flies, Drosophila. They have the same attraction in large part because of their short lifespan.

David Walker: [00:06:39] Yeah, that’s right, I mean, I’m perhaps somewhat biased because those are the two model organisms I’ve focused on in my in my career, but the vast majority of our understanding of the basic biological mechanisms of aging have come primarily through discoveries in those two model organisms. Of course, a lot of that work has been built upon and validated in rodent models and other mammalian models. But the initial discoveries of which genes, which pathway’s initially came out of, almost entirely out of research in those two invertebrate genetic models.

Peter Bowes: [00:07:17] So after initially starting studying genetics, you became increasingly interested and fascinated by the aging process, has your understanding of what aging is and so your definition of aging, has that evolved over the time that you’ve been studying it?

David Walker: [00:07:34] Yes, for sure, for sure. So I started studying, thinking about aging in the mid 1990s, so 25 years ago and you know, it would be stated no, as many of us still do today, that aging is a great scientific mystery. And there’s a lot of mysteries to aging today. But back then, that was not hyperbole. That was you know, we really didn’t know almost anything about what was aging at a cellular level, which changes that occur actually drive age related health decline. And really, it’s been in the last, I would argue, 10 years that our understanding of what really is driving aging at a cellular level has really increased. Now people still argue there are those that still argue that aging may not be a damage accumulation hypothesis. I think the evidence is pretty good that the accumulation of damage to cellular components, proteins, lipids, organelles, does drive the aging process. Some people would still argue against that, but I think it’s pretty compelling at this stage.

Peter Bowes: [00:08:58] And is it fair, then, to say that the focus of your work is on looking for potential interventions that could mitigate the effects of that damage and the as I mentioned it earlier, the negative effects of getting old, the physical decline and the mental decline as well.

David Walker: [00:09:14] Yes, absolutely, absolutely. And speaking of, you know, sort of evolutions in my own career and in my own way of thinking about this, you know, when I was a year studying for a Ph.D. or, you know, even a little later, you know, when you’re in when I was in my 20s, it really I really did think of it as a purely academic problem, a purely curiosity driven program, because perhaps, you know you know, at that stage of your life, you’re not quite as focused upon age-related health decline. And and it’s not so much as if the strategies change, because to understand aging at a cellular level, cellular level, I would still argue you do have to intervene. There’s a limit to how much we can really learn by simply measuring what changes with age. You’re always going to come up against the problem of whatever you see change. How do you know that’s not a correlative of aging or a consequence of aging? When you intervene using genetics or small compounds or diet or whatever, then that that gives confidence that whatever you’re studying, whatever, you know, molecule, gene pathway that you’re manipulating is causally or mechanistically involved in the aging process. So, yes, absolutely. A major focus of our work to this day is not only to understand what changes take place with age, but to try and develop novel ways, primarily using genes. But we can discuss other approaches where more recently taking but to to prevent those changes from taking place and prevent age-related health decline.

Peter Bowes: [00:11:10] And just a little aside, you mentioned that perhaps when we are younger, we don’t really think about aging as much or perhaps even as at all, because there is perhaps that sense that we are, you know, so far away from being very old that it’s something we don’t need to concern ourselves with. One thing I always try to get across to people who are significantly younger is that perhaps we would all be better off if we did start thinking about aging much, much earlier in our lives.

David Walker: [00:11:36] Yeah, I mean, of course, we’re familiar with it through, you know, our parents and certainly our grandparents, so it’s not something we’re oblivious to. But I think there’s very much when you’re young, there’s sort of an inevitable inevitability about it or sort of normalness about it that I think, you know, some of us are starting to challenge this concept of it. Does it, you know, really have to do we have to lose as you as you say, our physical or mental capacities so dramatically with chronological age?

Peter Bowes: [00:12:14] So let’s dive in a little deeper into the work that you’re doing in terms of cells and cell health. What is the main focus?

David Walker: [00:12:23] Yeah, so for the most part, I’ve sort of taken an approach over my career, which is to let the data drive the the hypothesis. So not so some people may say, oh, I’m going to say telomeres are important for aging or free radicals are important for aging, and then go after, you know, genes or components that that alter we’ve been fairly broad and open minded as which which genes and approaches. And we’ve even earlier in my career done unbiassed genetic screens. But in the last five or six years, the data has been telling us that the accumulation of dysfunctional mitochondria seems to be a really, really important cellular hallmark of aging. Now, of course, that’s not something that that my lab has discovered. The idea that our mitochondria, you know, become less efficient, less effective with age, has been around, frankly, for decades. But there were a lot of unknowns and a lot of speculation as to how that occurs. Can we prevent it from occurring? And what what are the consequences of that? And in the last decade, I would say we’ve really started to focus on a cellular pathway that recognizes and removes dysfunctional mitochondria, and that is proving quite fruitful for us. We’ve identified now a number of interventions that we can target that that pathway. So the pathway is called the pathway of mitochondrial autophagy. And I don’t know if I should back up and explain what we think autophagy is.

Peter Bowes: [00:14:22] I think it’s always good to explain that we have covered autophagy and mitophagy

David Walker: [00:14:26] Ok.

Peter Bowes: [00:14:26] quite a lot on the podcast, but I think it’s always good just to repeat, and I usually describe it as the way that our body gets rid of cells that are perhaps past their sell by date, not quite working properly, its cells, eating cells to regenerate and to come out of the end of a stronger.

David Walker: [00:14:42] Yeah, actually, recycling the components within a cell, the proteins, the organelles, the lipids, and it was a pathway that was initially thought to be very important under nutrient deprived conditions, under starvation conditions. But it turns out it seems to be very important, as you just said, for sort of maintaining general cellular health. So, I mean, one very perhaps overly simplistic way of thinking about it is it’s kind of like a garbage disposal or recycling unit within ourselves. And yeah, so so we’ve become yeah, in the last 10 years, focused on developing primarily, again, genetic interventions. But we have more recently got into looking for small compounds that could activate this pathway to get rid of those damaged mitochondria that accumulate with age. So again, this the idea that this damaged mitochondria are present in old organisms to a greater degree than in young organisms isn’t a novel idea. It’s been around for a long time. But the question of why does that happen? And so increasingly, I think we can build the argument that one of the major reasons is that this pathway, it’s not that the mitochondria aren’t getting damaged in a young animal. I think they are. But the machinery that removes the damaged mitochondria is functional and active when we’re young and as we age, the mitochondria continue to be damaged. But the machinery that recognizes those damaged mitochondria and targets them for degradation starts to decline in its function and activity. And that’s perhaps why the dysfunctional mitochondria accumulate with with age.

Peter Bowes: [00:16:36] And this is a pathway, I’m assuming here, this is a pathway that operates in different ways, according to individuals, so we’re not all the same were not all aging in the same way. And perhaps it explains why or maybe it doesn’t explain, but it’s a fact that some of us will age better and the physical decline and mental decline will be slower in some individuals than others.

David Walker: [00:16:59] I think you’re absolutely right, and I think we can all see that around us and in people, of course, it’s extremely challenging to try and, you know, figure that out. Is that due to changes, differences in diet, differences in lifestyle, socioeconomic conditions, many, many different factors at play. But as you may know, and even under laboratory conditions, fruit flies and nematode worms that we try and keep under as close to identical conditions as we possibly can, meaning they all eat the same diet. They’re all kept at exactly the same temperature, humidity, etc. Even there there’s a large degree of individual variability in certainly lifespan. And we’re starting to think in the rate of aging. And that actually brings us to another major focus of the lab, which we were interested in trying to understand, as I just said, aging at a cellular level. But we’re also fascinated by the pathophysiology of aging. How do age related changes that affect organ function relate to the health and viability of the aging organism? And so, again, that individual variability in rate of aging is not certainly not unique to people. It is something that occurs under tightly controlled laboratory conditions in fruit flies, for example. And again, around 10 years ago, we made an observation that I think helps us understand this a little bit better, and that relates to an important pathophysiological change that occurs with aging, and that is the loss of the function of the intestinal barrier. So that is something that we’ve been studying again in flies for around 10 years now. And we find that that’s very important in terms of the health of the fly. And since we reported those findings in drosophila, we’re very intrigued to see that many other groups now are reporting that loss of intestinal barrier function is a critical pathophysiological hallmark of aging in and in worms, in fish, in rodents, in non-human primates, and even, it would seem, in people.

Peter Bowes: [00:19:40] This is leaky intestines.

David Walker: [00:19:42] Yeah, so so that’s right, that was something we didn’t think didn’t certainly didn’t set out to study. It was one of those serendipitous discoveries where we were measuring feeding behaviour in Drosophila. And one of the ways you can do that is by feeding them a dye and non absorbable a day that typically doesn’t cross the intestinal barrier. And we find that every so often you would see a very old fly where the dye would leak out of the gut. And this this provided us an approach because it’s a non-invasive assay, you know, like they say at the end of the movies, no animals are harmed during the making of this movie. No no animals are harmed during this this assay. So we can actually measure other aspects of aging upon visualising the loss of intestinal barrier function. And so now we’ve linked this to many systemic markers of aging, including including inflammation and metabolic decay. And critically, it seems to be a harbinger, a predictor of mortality. And it certainly seems to be an evolutionarily conserved hallmark of aging, meaning that it’s something that isn’t unique to fruit flies and isn’t even unique to invertebrates, but something that becomes a problem with age and again, another sort of pathophysiological hallmark of aging of course, that’s been fairly well documented, especially in people is overactivity of the immune response, inflammation. And as we all know, inflammation is also linked to a fairly broad range of age onset diseases, including many neurodegenerative diseases. And again, one of the mysteries there had always been what is driving this age onset activation of the immune response. And again, in drosophila at least, although others have validated this work, at least in rodents. And there’s a number of studies in non-human primates as well to say that the leaky gut and perhaps changes within the population of bacteria that live within the gut seem to be an important factor that drive age onset inflammation. And again, that provides not just understanding of this important hallmark of ageing, but perhaps gives us hope as to a potential way again, to intervene. And if we could delay or even prevent age onset inflammation, I think the benefits to health would be enormous.

Peter Bowes: [00:22:28] Which is why, obviously, diet is so important in terms of the makeup of the different foods that we eat, but I just wanted to go back to talking about the variability of how we all progress in our lives and the pathways and the mechanisms involved, how we are all essentially very different in some respects. Maybe some of us are similar, but some of us are very different. And I guess that makes creating and delving into the science behind any interventions all the more complicated, because you’re not just focusing it on one type of individual. We are a human race that’s very, very different.

David Walker: [00:23:04] Yeah, I agree very strongly, I think as the field progresses and the field is made a lot of progress, that will become the next major challenge, that it’s entirely possible that some of the interventions that we all think about as being, you know, the go to your best case, pro longevity, anti aging intervention will indeed be helpful for certain individuals, but may not be helpful for others. And so I think you’re right. I think there are many more questions about individual variability in lifespan than we have answers. But are working flies with the intestinal barrier has started to make me think about this, at least through that lens, because one important source of that variability could come from changes within the intestine and perhaps even changes that occur within the population of bacteria that live within the intestine. And some of that variability that we all know and recognize in individual variability may actually have its origins within certainly within the intestine and possibly within the gut bacteria within the intestine.

Peter Bowes: [00:24:36] And you’re talking about the gut microbiome here, just one of the many microbiomes that exist within our body, which we’re increasingly becoming aware of as being so crucially important. Really going to the heart of what we’re talking about.

David Walker: [00:24:48] Yeah, exactly, and again, this is, you know, a dynamic area of research, this is something that, you know, is changes in gut bacteria are being linked to many diseases and potentially even linked to therapeutic interventions. One interesting observation, and this is again, this is not an observation unique to my lab and others have reported this as well, is that if you remove the gut bacteria from a population of aging fruit flies, you actually would typically reduce individual variability in longevity. What I mean by that is you sort of plateau the survival curve. And one way of interpreting that, of course, is, again, that that’s consistent with the idea that a lot of the individual variability comes from changes in gut bacteria. And so a number of years ago and we were able to show that one, this loss of intestinal barrier function is actually one important factor that seems to contribute to that is indeed changes in gut bacteria. And we could actually we could actually document and observe that some of the changes in the gut bacteria occur before the loss of intestinal barrier function and are actually predictive, again, of loss of intestinal barrier function. So so from these sorts of data, you can start to build a model of pathophysiology of aging, but also of how therefore individual variability could come about.

Peter Bowes: [00:26:35] And so then it begs the question, and you can extrapolate that to what are we all doing that affects the variability of our gut environment and only comes down to essentially what we are eating. If we’re not involved in any other external interventions, what do we do to change things in our gut where we change our diet, we modify our diet.

David Walker: [00:26:56] Yeah, you’re absolutely right, I would I would agree and assume that a major factor that that alters the composition of our gut microbes microbiota, as you say, is what we eat. And, you know, I think this is being studied quite extensively. And there are a lot of studies on that in people. And I can perhaps speak most. We spoke with most authority on Drosophila diets. And certainly what we see in Drosophila is high protein diets seem to be very bad news for the aging gut. So if we and others have also reported this grow flies age flies when they’re eating a low protein diet. This delays the the the onset of this important intestinal pathology that we’re studying. In other words, reduced protein intake maintains the gut barrier for longer and is also associated with a long, much longer and much healthier lifestyle. Again, that’s in Drosophila. But there is increasingly evidence, at least from rodent studies, that low protein diets can can be healthful, helpful for the for the aging organism and aging good as well.

Peter Bowes: [00:28:22] And of course, there are other aspects of longevity research, I’m thinking of the work of Valter Longo at USC

David Walker: [00:28:29] Yes. Yeah.

Peter Bowes: [00:28:29] In terms of low protein diets that support that theory in human beings.

David Walker: [00:28:33] Yeah, for sure, for sure. And again, I think the answers will be will be complicated and there may be other ways to achieve healthy aging, but but one way, maybe a low protein diet. And there’s even recent data in both intracellular and also mice that just reducing certain amino acids in the diet can provide health benefits with age.

Peter Bowes: [00:29:01] So what is maybe just broaden this out a little bit, then, what is your view of supplementation? And the and I talk to so many people about this, the challenges that we face in terms of how we can educate ourselves about what, if any, supplements are beneficial to us as individuals. Just bearing in mind exactly what you’ve just said about us all being a little bit different and the variability of what’s happening inside our guts, I think there’s an acknowledgement that none of us eat a perfect diet these days and that there are gaps to be filled and we can fill those gaps with with supplements. But how do we make those decisions?

David Walker: [00:29:37] I agree that it’s a challenge. The good news is every week and certainly every month we have more information, meaning that there are peer reviewed studies being published using model organisms and looking at some of these questions. And we increasingly have a better understanding of, again, which cellular pathways may be important to be able to modulate to gain health benefits. So, you know, many of the many die, you know, a lot of dietary advice. Let’s just take the low protein diet, for example. To my knowledge, this has not been definitively proven, but a very reasonable hypothesis to to understand why would eating less protein perhaps promote longevity? Is that eating high levels of protein activate an important nutrient sensing pathway in our bodies called the TOR pathway are the Target of Rapamycin pathway. And so I’m increasingly hopeful that we’ll be able to make better informed decisions based upon a lot of this work that’s going on, you know, across many labs, all throughout all throughout the world, and identifying pathways that are important to the aging process. And if we can tie those pathways to perhaps suppliments or nutraceuticals or small molecules that can target those pathways, then I think that would increase our confidence that that might be an appropriate approach to take.

Peter Bowes: [00:31:29] And as you say, there’s new research all the time, I’m just curious, in your own life, how do you apply your knowledge, your research, your findings over the years that you’ve been doing this to your lifestyle? Because, you know, we could wait five years, you wait 10 years, maybe 20 or 50 years to get some of the questions, the big questions that we have fully answered. But we won’t necessarily live that long. We’ve got to make decisions now and next week. I’m just curious how you live your life according to the science that you understand right now.

David Walker: [00:32:01] Yeah, so I do try and practice what I would suggest is common sense lifestyle goals, you know, which, you know, staying active in the last year has become increasingly a challenge with the pandemic and the associated restrictions. But staying physically active, certainly, I mean, I’m not aware of any, you know, many if any studies, you know, saying that being physically active is detrimental for aging, trying

Peter Bowes: [00:32:36] And fact, on the contrary, there are plenty of studies that suggest it’s it’s very beneficial to…

David Walker: [00:32:41] Exactly.

Peter Bowes: [00:32:41] ….counter the effects of aging.

David Walker: [00:32:43] Exactly, exactly. And the interesting question, of course, is, again, through which cellular pathways and that, again, I expect to be a growth industry in the next, you know, a number of years trying to to understand that in terms of diet, perhaps inspired by some of the studies, in drosophila saying low protein diets, I don’t eat a lot of meat. I don’t eat a lot of red meat. I, I, I love eating. So it’s not I’m not one of these people who can, you know, easily, you know, restrict all dietary intake or anything like that. So, you know, try and eat a diet, which is mainly plant-based mainly and probably almost as importantly, not too much. You know, to not eat the quantity of what we eat as well as the quality is going to matter a lot. But again, without getting too philosophical and as I say, I love to eat. So I again, I think quality of life is very important as well as quantity of life. And there’s there’s enormous social benefits to eating together. And, you know, that’s something sharing, you know, sharing food with others is one of the things that make life meaningful and wonderful. And so it’s not something I would ever want to to give up. So, you know, from time to time, I try and balance it out. If I eat a lot one day, maybe not so much the next day or go for a longer run the next day.

Peter Bowes: [00:34:17] I’m just curious in terms of your research with with Drosophila –  fruit flies – and nematodes before that. Is there anything that you can say about cognitive ability as we grow older? Clearly, dementia is a huge and increasing issue for our populations right now. And, you know, it all seems to come back to the gut in some in some respects that I think there are certainly links between the the gut makeup and mental abilities. Have you looked at anything like that?

David Walker: [00:34:46] Not yet in any great detail, but what I can tell you is a couple of things. So just as is the case, as you just said, in us, fruit flies become more forgetful as they get older. And that is that’s fairly well documented. And I think we’re we’re starting to understand in a more clear manner that perhaps the the same cellular mechanisms that are important in these devastating diseases of the aged brain. Alzheimer’s, for example, are shared mechanisms with the aging process. So I mentioned, you know, a few moments ago the accumulation of dysfunctional mitochondria. So so that is a well documented cellular hallmark of aging. It’s also linked to the diseases of the aging brain, Alzheimer’s disease, Parkinson’s disease. Another major cellular hallmark of aging is the accumulation of aggregated or misfolded proteins. And that also is not only a hallmark of aging, it’s a hallmark of Alzheimer’s disease. It’s a hallmark of several neurodegenerative diseases. So I remain optimistic that interventions that we and others can discover that prevent the accumulation of dysfunctional mitochondria, interventions that prevent the accumulation of aggregated or misfolded proteins will be beneficial or will help delay the onset and progression of these neurodegenerative diseases. I think there’s a lot of reasons for for optimism there.

Peter Bowes: [00:36:33] And you mentioned fruit flies become more forgetful as they get older and it’s well documented. How do you measure that?

David Walker: [00:36:40] Yeah, so you can measure memory in fruit flies by pairing something either positive or negative, something that they like or something they dislike with a specific odor. And then if it’s something they dislike, you can repeat the experiment with only the odor and see if they act like they dislike it or vice versa. So it’s somewhat Pavlovian in its nature and that it’s been known for maybe almost 35, 40 years now. And that flies can remember, for example, a mild electric shock. And then, you know, and if you pair that with an odor, they’re going to associate that with with the negative stimulus.

Peter Bowes: [00:37:27] It always it’s endless fascination to me that fruit flies and nematode worms can be very, very accurate models for human beings, you wouldn’t think it, but they can be.

David Walker: [00:37:38] Yeah, no, no, I hear I hear what you’re saying, and I think it will turn out that, of course, you can’t model everything in an invertebrate model, but so far the data has been extremely positive in terms of the interventions that were initially discovered in those model organisms turn out to be potential targets in in people and especially for neuromuscular diseases, neuromuscular aging. I think flies and worms seem to be really, really terrific models.

Peter Bowes: [00:38:14] Just as we close, I often ask people this, as you look at your own life and the progression of your life, do you have aspirations as it applies to longevity and getting older? You’ve described your your healthy lifestyle, but is your own longevity something that you give a lot of thought to still as a relatively young man?

David Walker: [00:38:34] Yes, I yeah, I, quality of life is something that’s incredibly important to me, I love to read. I love to think. I love to learn, I love to experience. I love to be. One of the things I look forward to is actually, you know, going for a bicycle ride, going for for a run and being physical, being physically active. And so, yeah, the idea that these things would be taken away gradually or otherwise is not something that I take lightly and something and of course, I see it with my mother’s in her mid 70s, is still in good health. But again, you just don’t want to see these things slipping away. I’m I’m a big believer in this is it. This is our life and we have to make it count. And you know what makes us happy in our everyday life and in the longer term, it is really important. And for me, being mentally active and as importantly, physically active is incredibly, incredibly important to me.

Peter Bowes: [00:39:48] And does living, I guess it does, living in Santa Monica, California, probably helps in that respect. It’s a question now coming from the UK. I often get asked about the just the the atmosphere and the the encouragement sometimes that you get in a state like California to look after yourself.

David Walker: [00:40:03] I do think that we can play a role for sure. Certainly the climate helps a lot being able to, you know, focus pre pandemic where we can all, you know, go in as we choose. But and the idea that you can be physically active outdoors almost any day, you know, through throughout the year is really appealing. And, yeah, perhaps being surrounded by, you know, living somewhere where it certainly looks to be where most people seem, you know, focused on living a healthy lifestyle, can can also sort of, you know, help as well.

Peter Bowes: [00:40:45] Yeah, and before I sound or maybe even making you sound too smug about the fact that we’re living in California, you can do these things clearly. We can exercise, we can live healthy lifestyles anywhere else in the world. I think we perhaps are a little bit privileged and lucky to live in a beautiful environment like this. But clearly, it doesn’t preclude exercise. It doesn’t preclude a healthy diet, I would argue, anywhere…

David Walker: [00:41:06] No,

Peter Bowes: [00:41:06] …in the world.

David Walker: [00:41:06] Absolutely not, absolutely not. I think we can all make time, no matter, you know, to do our best to, you know, focus on our own individual, you know, health. I always see it as a way, you know, you’re not wasting time, you’re buying time. You know, future time, hopefully.

Peter Bowes: [00:41:25] Yeah, I think that’s a great way to finish this, David. Fascinating conversation. Thank you very much indeed.

David Walker: [00:41:30] Thank you. It was really interesting to talk to you.

Peter Bowes: [00:41:33] And I will put into the show notes for this episode of the podcast, a link to your David, your website, your university website. If anyone wants to dig a little…

David Walker: [00:41:41] For sure.

Peter Bowes: [00:41:42] …deeper, you’ll find that at our website, LLAMApodcasts.com LLAMApodcasts.com, that’s the Live Long and Master Aging podcast website. This is a Healthspan Media production. If you enjoy what we do, you can rate and review at Apple podcasts. You can follow us in social media @LLAMApodcast and you can direct message me @PeterBowes  Do take care. And many thanks for listening.