Buck Institute research on Urolithin A for Alzheimer's

Podcast featuring researcher Julie Andersen from the Buck Institute for Research on Aging talking about gut metabolite Urolithin A

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Live Long and Master Aging

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Cognitive decline is an all-too-familiar hallmark of age-related diseases, such as Alzheimer’s and Parkinson’s. While there is much research that focuses exclusively on functional changes in the brain, the so-called gut-brain axis – a connection between the digestive system and the central nervous system – also appears to play a pivotal role. It raises the question:

Could nutritional interventions, to nurture the health of the gut microbiome, also help prevent or reverse age-related dementia? In 2018, Dr. Julie Andersen, a scientist at the Buck Institute for Research On Aging, in California, received a $3.8 million grant to explore the hypothesis. In this LLAMA podcast episode, Dr. Andersen discusses the work of her laboratory, and the idea that a gut metabolite, urolithin A, could play an important role in the treatment of Alzheimer’s disease.

Transcript
Speaker 1
It would be great to live longer. But who wants to live longer with Alzheimer's disease? So the great hope is that we're going to be able to eliminate these diseases and allow everyone to live a healthy, long lifespan.
Speaker 2
Hello again, and a very warm welcome to the Live Long and Most Ageing podcast. My name is Peter Bowes. This is where we explore the science and stories behind human longevity. This episode is brought to you in association with Amazon, a Swiss life science company that's pioneering, cutting edge, clinically validated cellular nutrition under its timeline brand. Now, earlier this month, it was revealed by his family that one of the greatest singers of all time, Tony Bennett, has Alzheimer's disease, the most common form of age related dementia.
Speaker 2
He is 94 years old now. And according to what I have to say, is a very moving piece in the AARP magazine. He was diagnosed in 2016. And now some five years later, the article says even his increasingly rare moments of clarity and awareness reveal the depths of his disability, memory loss and a detachment from reality are typical of this brutal disease, a disease that I think most of us have probably experienced in some way, family members, friends, neighbours.
Speaker 2
It is on the increase and there is still no cure, which is why I, for one, devote every bit of new research in the hope that one day we will not have to fear what is often called the long goodbye. And talking of new research, there is a study underway that's particularly caught my eye because it involves a compound that we on this podcast have discussed a lot over recent months. My guest is Dr. Julie Anderson, a researcher at the Book Institute for Research on Ageing.
Speaker 2
Just to the north of San Francisco, here in California, Dr. Anderson recently received a three point one million dollar grant from the National Institutes of Health to study the potential benefits of Allison as a possible treatment for Alzheimer's disease. Dr. Arneson, welcome to the Live Long and Most Ageing podcast.
Speaker 1
Oh, thank you very much for for having me.
Speaker 2
It's really good to talk to you. We'll do a recap on what year Allison is in a moment. But tell me about working at the book. I did an interview with Eric Verdin, the institute's president, for this podcast, shortly after he was appointed. And I still haven't managed to take him up on his offer to come and visit. Hopefully I will one day. But I think it's fair to say, isn't it, if you're interested in ageing and the signs of ageing, it's the place to be.
Speaker 2
It's the place to work.
Speaker 1
Yeah, absolutely wonderful place. I've been there over 20 years now and I'm really a neuroscientist and I probably could have ended up in a neuroscience department or neurology school. But I have to say, I really love working at the park. It's it's still the only free at a standing institute studying ageing and age related disease. And that really gives a breath to the type of research that we do, rather than studying diseases and silos and dependent from the ageing process, were really concentrated on what it is about ageing itself that drives all these disparate diseases.
Speaker 2
And I think one of the interesting things about the place is the multidisciplinary approach that you're not just looking at ageing from one perspective. And I think that's where a lot of the the energy must come from in terms of working in those laboratories.
Speaker 1
Yeah, it's really amazing. I have to say that when I first came to the park, there was another faculty member who happened to be a cancer biologist. And, you know, your first thought is so that's the work is really interesting. But really, what is cancer have to do with Alzheimer's or Parkinson's disease? But it turns out that a lot of these basic ageing mechanisms drive very different age related diseases. And I think it's very exciting to work at the back in the sense that we're very collaborative and we kind of work across different fields at looking at these basic mechanisms that that drive ageing and age related disease.
Speaker 2
What first got you interested in ageing?
Speaker 1
I mean, I have to admit that when I was I'm in college, I started to develop an interest in studying the brain. So neuroscience and it just happened that the laboratory that I ended up in at UCLA for my graduate studies and I think things often in life are fortuitous, the way it happened to be a lab that was studying Parkinson's disease. And when I went on to my post-doctoral fellowship. At Mass General Hospital in Boston, I really was targeting labs that were studying Parkinson's disease and to some degree, fortuitously, again, when I was looking for my first faculty position, I, I was hired by the School of Gerontology at USC.
Speaker 1
And I think that that was really what opened my eyes to this notion, which is now very widely accepted, this idea of general science, which is that there are basic mechanisms which occur in almost every cell in the body that that are are involved in driving ageing and like many, many, many different organs and tissues. So I buy time at address. Gerontology really got me started thinking about ageing and how it relates to seasons like Parkinson's and Alzheimer's disease, and that I move to the the back in 2000.
Speaker 1
And that's just been a wonderful experience for me.
Speaker 2
And I think what's interesting and you have probably a much better perspective on this than I do that in terms of the respectability of studying ageing as a discipline, how that has changed over the decades. And I think there was certainly from talking to other scientists on this podcast to get a sense that a few decades ago, if you said you were studying ageing, it wouldn't necessarily be taken that seriously, because it isn't biochemistry. It isn't physics. It isn't mathematics.
Speaker 2
It is, I suppose, a combination of all of those things.
Speaker 1
Yeah, I think that's absolutely true. I, I think in the nascent years of of biology, of ageing research, because we knew so little about it, I think there are there was a lot of scepticism and a lot of concern about, I guess what I would call the snake oil of fact, that people were touting different therapeutics in terms of ageing without really knowing enough about the process. But I think fast forwarding a decade or so, we really have been able to drill down on precise molecular mechanisms that are involved in ageing and having having been on the field for 20 years, it's really like burgeoned over the last five, 10 years and really is is taken very, very seriously.
Speaker 1
I think we're kind of in the Renaissance, I would say, of ageing research, which is wonderful. It's wonderful to be a part of that.
Speaker 2
And with a better understanding of those mechanisms involved. Does it help you produce a concise definition of what ageing is? It's not an age old question that so many people pose, and we still get very different answers in terms of what it is and what it entails, whether it's a disease itself or whether it's just an umbrella term to describe a number of diseases that affect us as we get older. What do you say to that question?
Speaker 1
I mean, I think that that's very true. I think there is still a fair degree of controversy in the field about what the exact definition of of ageing is. The rubric that we at the box sort of operate under is this rubric of neuroscience, which I have to say was a term which was coined at the back by Gordon Lithgow, who's a fellow faculty member, and actually as my spouse. And it was part of a central grant that we got on doing very doing.
Speaker 1
What do I want to say, diverse sort of integrative science. And we he coined this term neuroscience with which is sort of this overarching idea that ageing just isn't just a risk factor for all of these different diseases, but it's actually the underlying driving force. And that we are we have the ability to define precise molecular mechanisms that are common amongst these different diseases that are acting to to exacerbate and to propagate the diseases.
Speaker 2
And for the audience of this broadcast, I always try to dig beneath the jargon or at least try to eliminate some of the jargon from the discussion under one phrase. I don't know whether it's jargon or not, but one phrase, of course, that we all hear a lot is simply anti or anti ageing. I don't really know what anti ageing is. I consider personally myself that ageing is still something that's moving forward as opposed to something that is maybe stationary or could be even reversed and.
Speaker 2
Turned backwards, is is anti ageing, is it just a marketing term, do you think?
Speaker 1
I think it's a term that a lot of people use. I mean, I have to admit, I'm I'm a basic research scientist, so I probably are on the side of being more conservative. I, I, I'm not sure whether we'll find out as research progresses. I'm not sure whether we will be able to reverse ageing. But, you know, to be honest, to be able to slow the process in the hopes that everybody's going to be able to, let's say, live to the age of 90 or above and not have major age related diseases.
Speaker 1
I think that's what most scientists in the field are really, really hoping for. It's so to some extent, it's not. I mean, early in the biology of ageing field, I think a lot of the emphasis was on longevity or increasing lifespan. And I think the emphasis is really sort of turned in the last several years towards health span. So the idea of yeah, so it would be great to live longer, but who wants to live longer with Alzheimer's disease?
Speaker 1
So the great hope is that we're going to be able to eliminate these diseases and allow everyone to live a healthy, long lifespan.
Speaker 2
Yeah, and I think that very neatly brings us around to what we consider most of the time today. Talking about that is research surrounding Alzheimer's. And certainly in recent months on this podcast, we've talked quite a lot and quite extensively about your health in a way which is this compound derived from fruits, pomegranates in particular, which can play a central role in mitochondrial health. The energy centres of our cells can help maintain at least the processes and the mechanisms involved can help us with our muscular strength, prevent frailty in old age, which is a crucial issue for anyone who is getting old.
Speaker 2
It's often the beginning of the end of frailty sets in and people succumb to falls and that kind of thing. So that's why the muscular strength is important. But what I find now fascinating, relating it to your work is the potential for some relationship with Alzheimer's. So let's start from the beginning. How did you first become aware of your role within A and explain its significance?
Speaker 1
So as I said, I'm a I'm a neuroscientist. So we study processes which allow the healthy maintenance of of neurones in the brain. And one of those processes is something called autophagy. So autophagy is something that's undertaken by an organelle and the cell called the lysosome. You can kind of just like the body has organs, the cell has organelles, the the nucleus is the the brain of the cell. Mitochondria, which you mentioned, are sort of the energy producing plants of the cell.
Speaker 1
We you have these other organelles called life systems that are important in terms of getting rid of defective proteins and also organelles that have become defective like mitochondria. So these damaged cellular components are are tagged and they're taken up into the lysosome and they're broken down into their component parts. I kind of think of the system as being the recycling centre of the cell, and those parts can then be reused to make new functional proteins on new functional organelles like mitochondria. So we had a lot of interest in this idea of protein turnover and turnover of defective mitochondria.
Speaker 1
And we were looking for compounds that were restoring lysosomal function and therefore producing functional proteins and functional mitochondria. And we'd actually been screening for drugs to look for compounds that fulfilled that function. And at that time we happened to notice paper, which was about five years ago from our lab where they had been looking at your life. And a and what really intrigued us was that they were looking at UAI and the context of both longevity. So they were looking in these little invertebrate models of ageing called Silicon's little worms that people used to study ageing related genes.
Speaker 1
And now a lot of studies are ongoing to look at compounds that extend lifespan. And these were. It's pretty amazing because you think what do we as human beings have in common with worms? But it turns out that a lot of the basic biological processes which drive longevity and and ageing are conserved evolutionary and in these animals. So if you're screening these animals for a drug that increases longevity, it very well may increase longevity in mammalian species, including humans.
Speaker 1
And not only that, as I alluded to before, it can also increase health span by by allowing the formation of new functional mitochondria. And in in this paper, what was really exciting to us, the investigators looked at the ability of your life in a normal ageing mice to improve, as I think you mentioned, muscle function. And that's pretty amazing. I mean, muscle function is very important, as you said. It's one of the things that often even relation to diseases like Parkinson's disease, it's the effects on being able to have appropriate muscle function that that leads to falls and so forth, that can have devastating effects in terms of people's, you know, overall overall health.
Speaker 1
So we were very, very intrigued by that, that study and very interested in looking at the efficacy of your life then and some of our animal models of Parkinson's and Alzheimer's disease.
Speaker 2
And just before we continue, if you could maybe explain a recap for us, the processes and the mechanisms involved. And I mentioned your elephant and I mentioned pomegranates. The fruits are not exactly where we find the euro Luthan age, something that happens in our gut. Our gut metabolism is crucially involved and we all respond in different ways to the larger tannins, as they known, that are found in fruits. That's the beginning of the process. But we don't all necessarily then go on to generate euros within a to the same degree.
Speaker 1
Yes, precisely. And that is something that we were also very interested in terms of, of ageing. So it turns out that you're absolutely correct. You're alive then A is not the component that's found within health foods like pomegranate or walnuts, what have you, but it's actually a precursor cultic lactic acid. So a lactic acid within those foods, when we adjust them, it actually gets converted by bacteria and the gut to your life in a and it's your life and then and the gut and can enter the bloodstream.
Speaker 1
And it can it can enter every organ in the body, including the brain. It's able to cross the blood brain barrier and get into the brain. It turns out with ageing, we often have what's called gut just biopsies are changes and are the bacteria and and other critters that are that are found within the gut, something called the gut microbiome with age and the the ability of the bacteria in our gut because of the change in the composition to convert compounds like a lactic acid to your life, then a decreases because of this change in bacteria.
Speaker 1
So one of the things that we were interested in was whether part of the reason or whether with older individuals, they may not be able to reap the full benefits of eating healthy foods like pomegranates because of this change in their gut microbiome. And if we could restore an older person's microbiome to that of a younger person, would that help them more easily convert their lactic acid in these foods into to EUA? Would that improve their ability to produce UAI and have the beneficial effects of your life?
Speaker 2
The day I mentioned we have talked about this before and we've talked about it in relation to and I mentioned again that this is a podcast in association with Amazon, which is the Swiss company that has developed a wholly pure form of euro called Moto Pure. And this is essentially a nutritional supplement. And for all the reasons that you have described in some detail as to why, it is important that as we grow older, we have levels of utilising a that can perhaps work for us on many different levels in terms of preventing.
Speaker 2
Some of those killer diseases potentially as we grow older, so I'm interested to know how has the work of incentives and there've been a number of clinical trials so far. How does that complement the work that you're doing?
Speaker 1
Yeah, we were very excited to see their their initial published clinical trial looking, you know, in humans and looking at the efficacy in older humans of your life in a way to enhance muscle function. So normally in science, we run what are called preclinical trials where we we look at, let's say, a compound and a mouse model of a disease or during the ageing process. And that then moves to a human clinical trial where we're seeing whether the same holds in humans.
Speaker 1
So we were very excited to see the earlier findings from the from the outside group in mice and ageing mice or replicated in the small clinical trial in in humans. And actually, they went a step further and they were looking to see to look molecularly at the impact if you're alive then and the muscles, whether that involved enhanced mitochondrial function and the data from their studies simply indicate, yes, that was that was the case. So that's very it's very, very exciting when you see something that seems to work well in terms of preclinical basic science studies, that it can be moved into human populations, because honestly, that's that's why we all do research and that's what we're what we're wanting in the end, to be able to be able to show a clinical effect in humans.
Speaker 1
So fantastic.
Speaker 2
I think what a lot of this highlights is the increasingly understood importance of the microbiome.
Speaker 1
Yeah, absolutely. Were you aware part of the interest, to be honest and in your life and in our study was part of a larger interest that the lab has in the role that the microbiome plays and diseases like Parkinson's and Alzheimer's? We used to think of these diseases as being brain centric, that that all of the things that go wrong have to do with the neurones in the brain. But it actually turns out that it may very well be, for example, in the case of Parkinson's disease, that the disease actually starts in the gut, that there are changes in the gut microbiome, which causes an increase in inflammation, which can affect the inflammation of the brain.
Speaker 1
You can have a change in the gut microbiome producing and inflammatory factors that can then enter the bloodstream and into the brain and cause inflammation in the brain and neurodegeneration. And you also can be affecting the production of different metabolites that we need that are produced in the gut and released into the circulatory system and cross the blood brain barrier that are important for for brain function. And unfortunately, with age, we tend to have few, not only fewer bacteria, but the diversity of the bacteria that we have decreases.
Speaker 1
So we don't really have all the needed bacteria to make all of the nutrients and to damp down inflammation, thereby affecting the brain. It's interesting because in Parkinson's patients, the people who people there's a subset of people who end up being diagnosed with Parkinson's disease that 20 years before the fact had all sorts of gastrointestinal issues, IBD and constipation and etc. And we're realising that there's a real molecular link there due to changes in the gut microbiome that can then affect the brain.
Speaker 1
So it's kind of opened up this whole new area of study. And in science, and particularly in age related disease called the gut brain axis, where some people got like a mini the mini brain. And and it's just it's been in terms of CNS disorders, it's been implicated in autism and schizophrenia. And now there is a lot of data backing up this. This gut despisers has changed in the gut microbiome and in Alzheimer's and Parkinson's to. This is so very, very interesting area that that you're life in is a very important part of.
Speaker 2
Exactly. And I was actually just going to say, I think the challenge for a lot of people is probably just getting your head around the idea that something that you might have otherwise or previously thought of as being a brain disease or a brain related disease when especially talking about losing your memory, that it does relate in a very significant way to your gut and and ultimately to what you eat.
Speaker 1
Yes, absolutely. So it is you know, we say you are what you eat. Absolutely. It's very, very important in maintaining a healthy diet is very, very important in and because you need you need to have a healthy gut in order to stop the production of these bad things that can get into the blood and get into the brain, these inflammatory factors, and also to keep producing important metabolites like short chain fatty acids that the brain needs to function.
Speaker 1
So there's absolutely a very strong connexion between the two.
Speaker 2
Just changing tack a little. I mentioned in the introduction that you have this three point one million dollar laboratory. How is this grant to to move forward with this research? First of all, I'm just curious, how do you get a grant like that? I think in the last 12 months, we've probably all become aware of the crucial importance of clinical trials, which will be well aware of are incredibly expensive to conduct. But how do you go about applying for and being awarded a sum of money?
Speaker 1
Yeah, it is a somewhat laborious process. So someone like myself who does basic science we are interested in and molecular mechanism, part of our interest in your life then is of course, we're very, very interested in its efficacy to prevent diseases like Alzheimer's, but we're also interested in the underlying mechanisms. Like what? What exactly is the compound doing that's so good for for the brain? Because by understanding the mechanism, we may be able to come up with other drugs that do similar things and might do it, might do it more efficiently.
Speaker 1
So in the process of trying to get funding in order to do preclinical researchers, we a large governmental agency which is involved in and funding basic research and clinical research in the US is the National Institute of Health, or NIH. And so you you write a grant asking the agency to to fund the project you're you're interested in. It goes to what's called peer review. So it's a group of people who have expertise in the area, let's say expertise in autophagy or expertise in Alzheimer's disease.
Speaker 1
The grant with a number of other grants. I actually sit on the study section in the studies section, we study section that reviews grants me it's about three times a year and goes so far, maybe 100 different grants. So you can see that there's a large volume of grants that come in asking for funding from the NIH. And in part of this peer review process, you receive a score, you're ranked with the other grants, and then the NIH is able to fund a subset of of those those grants.
Speaker 1
When I have to say when funding was really dire for ageing research, NIH was funding something like five to seven percent of all grants, which is a pretty small percentage. So you you put in a graduate five or six months until the studies section reviews. You get a score and then you wait another five or six months to find out whether it the grants are going to be funded by by the NIH. So there's a large period of time during the process where you're really once you've submitted the grant, you're just waiting to find out whether or not you got you got funding.
Speaker 1
But the good news is if you if you get funding normally fundings for three to five years, which is a good amount of time to allow you to explore your particular hypothesis, which in our case was that your life then would be something that that would that would prevent or improve Alzheimer's symptoms in a preclinical model. And that's a needed step in order for studies to be carried forward into clinical studies and. In humans, things are first studied preclinical, pretty clinically, and for example, mouse models of the disease before they're there are allowed to be carried forward into humans, including studies on the safety of the compound.
Speaker 1
That all has to be do so safety, how efficacious it is, etc. That's all done pretty clinically.
Speaker 2
And you mentioned that funding traditionally for ageing or age related projects has been quite difficult to get. Is that changing? And I guess one of the problems must be, but by its very nature, ageing is something that happens over a long period of time. And especially when you're talking about human trials, it's a little bit different with nematode worms or mice or fruit flies. But when you're talking about humans, if you want to see a cause and effect, it's going to have to be over quite a long period of time, which must make getting the funding for that over that period of time quite difficult.
Speaker 1
Right, exactly. And I think that that is something that makes the clinical trials in terms of ageing persay difficult because you are looking at people or ideally you're looking at individuals over a longer period of time. So, I mean, I have to say, even so, my my husband works on worms. Worms, soil against their lifespan are is to two weeks. So they're able to do studies when they're looking at lifespan or health span and that an invertebrate organism, they're able to do those pretty rapidly.
Speaker 1
The average lifespan of a mouse is three years. If you're looking at something like, I don't know, childhood type one diabetes and a mouse, you can look at young mice and you can do it more rapidly. Average mouse being three years. If you're looking at something like Alzheimer's disease, you're doing those studies over, let's say, one, two, three year period. So it's a little bit more elongated depending on the preclinical species that you're using.
Speaker 1
And ideally, you want to use a species that's most like humans as possible. Some people use primates for further studies and engines, but as you can imagine, their lifespan being 30 years and more, those are even more long term studies. So, yes, that is something inherent. And in funding both clinically and clinically for for ageing research that has to be taken into consideration. The FDA actually used are traditionally doesn't really if you're funded for a clinical trial, it's traditionally towards a particular disease as opposed to ageing, per say.
Speaker 2
So as you move forward with this research, can you give me an idea of of the stages in terms of looking ahead the next month and next year, the next three years in terms of the form of research that you'll be carrying out? What will you need to do?
Speaker 1
To be honest, the first thing that we had to convince ourselves what was our hypothesis was that giving a mouse model of Alzheimer's disease, that it was going to slow the course or, you know, stop the course of of or prevent the course of Alzheimer's disease in that and that mouse model. And we're kind of well into the middle of the study. These results are really preliminary, but we do have preliminary data that suggests that the the Alzheimer's mice that have been placed.
Speaker 1
So we are actually giving your life then in the field. So the the mice are taking it orally and in the feed, just the same way that a lactic acid is, you know, given in the in food to to humans. And our preliminary data says that this seems to be improving cognition are preventing the cognitive loss that you see associated with this mouse Alzheimer's model. So we're now in the process of actually looking at the brains from those mice, these these mice, this this particular mouse model that we're using, which is called a 3.x and transgenic.
Speaker 1
They actually produce the plaques and tangles within the brain that are very similar to what you see in in humans. So we're in the process now of the mice seem to have improved cognition. Is that due to the fact that they're not producing the same plaques and tangles that we associate with Alzheimer's disease in in humans? And so that's sort of. The stage we're at now, how do you measure the improved cognition in the mice?
Speaker 1
Well. So there are some very well established tests, which probably sound crazy to a lay audience, but there are some well-established cognitive tests. One that's the most well-established is something called the water maze or the Morris Water Maze, where basically you have a round large tub of water which is opaque and you put a little submerged stand at a particular location in this tub of water. And you put the mouse in there and you look you measure in time how long it takes that to find the platform.
Speaker 1
And so there's kind of a learning curve that goes along with that, that if you do that several times, the mouse will eventually learn kind of where where are the submerged platform is placed within the tub and will go more directly to it. And then you can do an additional test for you or you move the platform someplace else and see how much time it takes the mouse to get to that platform. So that's one of the and that is a test of the function of a brain area called the hippocampus in the mouse.
Speaker 1
And and it's the same area within humans that's impacted in an Alzheimer's disease. So there's several there's several tests like that which have been well-established to look at particular brain regions and how they're functioning.
Speaker 2
Interesting you say that it reminds me of a job many, many, many moons ago. I used to work for the Medical Research Council in the UK and I worked with mom was that monkeys are actually very similar to what you're saying. This is about you looking at cognitive issues, schizophrenia, Parkinson's disease. And my job as a laboratory technician at that stage was looking at the cognitive abilities of those monkeys that may be impaired in some ways and seeing how they responded to to visual stimulus.
Speaker 1
Yeah, I mean, part of this Waterman's is also visual because you have particular like you might have particular posters or something on the walls. And part of what the mice are processing is the placement of that stimuli and that that helps direct them to where the platform is. So, I mean, it's kind of amazing to me. But the but these techniques for looking at cognition have been established over decades. And in mouse models it is. And when you're actually doing this work, it is enlightening just to a large extent, just seeing how the ability of an animal, whatever the species of animal is, its ability to learn and to remember.
Speaker 1
And what animal is that? A lot of people wouldn't think about a mouse and its cognitive abilities, but. Right. Or the trials as well. But the existing big time.
Speaker 1
Yeah. Oh, yeah, absolutely.
Speaker 2
So what's the next stage you were supposed to go on to the next stage in the research.
Speaker 1
So, you know, we feel again, it's preliminary. I'm a basic scientist, preliminary. We need to repeat and be absolutely sure that the findings that we have are reproducible. But work, you know, we can't help but be excited that that we seem to be having effects. So sort of stage two of the process will be looking. So these are older, my sister mice that are like 14 months. So there's sort of, I guess I would say, middle aged mice.
Speaker 1
So we'll continue to look with increasing age. And also we want to start diving in more to this whole gut brain access. How much to Age-Related alterations in the gut? How much to influence does this have in terms of cognition, especially with the pre giving the animals a Lukšić acid, the precursor? If so, in a sense, you can give your life in a way which is the active compound or an older person might be eating, eating foods that have a Lukšić acid or taking a Lekic acid itself and then also maybe taking a probiotic.
Speaker 1
So re-establishing a healthy microbiome. And that would that be sufficient to raise levels of your life in a within the older individual to what would be therapeutic levels that would would help maintain cognition with age? So, yeah, very much interested in this microbiome angle.
Speaker 2
Yeah, it's fascinating. Of course, you're not doing this kind of research in isolation. We've mentioned the work of Amazon is in Switzerland as well, which is still ongoing. This is in many senses, a collaborative effort, isn't it, to try to better understand you're a listener?
Speaker 1
Absolutely. Absolutely. And so and I think that's the great thing about science, is when you can work together as a community and you have several different entities that are working on different aspects and finding out different things about how a particular compound works, that adds to the overall body of knowledge. And I think that's really not one lab can't do one lab or one entity can't relate to everything. And I think we all learn from each other. And I think that's great.
Speaker 1
That's one of the things I love about science.
Speaker 2
And that kind of brings me to my closing question. I ask almost everyone this based on the science, and you are a husband and wife team working on similar subjects because you say you must live and breathe this all of the time. I'm wondering how you apply the science and what you've learnt over the years, over the decades to your own life and your own longevity. Is it something that you think about?
Speaker 1
Yeah, I think it's sort of the good and the bad of working someplace where you're studying ageing. I think you think about it all the time. And I do think it impacts on like realising that exercise or realising that eating a healthy diet, reducing your stress level, you know, all of all of those things, I think it does really impact on your on your lifestyle. I mean, I have to admit, for fair or not, I, I do take a probiotic because I feel like that's a means of maintaining along with eating healthy food and even exercise, you know, that that's a way of maintaining a healthy diet.
Speaker 1
And therefore, I think a healthy a healthy body. So, yeah, absolutely impacts on on our our day to day lifestyle choices.
Speaker 2
And do you think about when you made the distinction for us between lifespan and health span, do you think about yourself in the decades to come and the kind of health span that you want to enjoy? Because I think that is the distinction that we are enjoying life while we have good health during that that window, that health span window, what is the lifespan window may not necessarily towards the end involve good health. So I'm wondering, as you as you look forward, do you have aspirations?
Speaker 1
Yes, very much so. I mean, it really this, you know, average age of onset of Alzheimer's is 75. The sort of dogma is people may be able to live a hundred and twenty. Do you want to live to 120 with Alzheimer's disease now? So everything that you can do to try to maintain your your health span and healthy living is really, really important to have to admit. I'm turning 60 this year. And I think that makes me think about it all, all the more as I start entering, which I guess society sort of considers being, you know, I don't even know what it's like a more elderly state moving towards 65.
Speaker 1
I think about it a lot. And, yeah, you just want to you want to be I hope that I can live a healthy lifespan for as long as as possible. And honestly, I hope I I don't develop any age related disease. The nice thing about that is so little of that or we've become more and more aware that so little of that is really genetic. There's some calculations that say that only seven percent of our ageing process is due to our genes.
Speaker 1
So there's a lot you can do in terms of environment to impact upon your health span.
Speaker 2
Interesting. And you mentioned turning 60. I turn 60 next year. Something about this this turning point isn't there that certainly personally it seems to affect you more. Yes. Turning fifty or turning 40 or turning 30 something about 60. And I haven't quite figured it out for myself. I don't know, because it's so much closer to the official retirement age.
Speaker 1
Yes. I don't know what it is. I mean, of course, scientists like never retire. People just keep working. But well, even even with that, I think I would I part of what I enjoy about being a scientist is we well, formally and hopefully shall return again. We were able to travel to meetings. And I am. Enjoyed that aspect of the job, and even after I retire, I'd like to continue travelling and reading and I don't know, just learning as I continue as I continue to age.
Speaker 1
But, yeah, it's absolutely true. There's something about 60 that is different than turning 40 or 50. And I don't really know what it is either.
Speaker 2
Maybe we'll figure it out. Just coming back. I mentioned in the introduction Tony Bennett being diagnosed with Alzheimer's, which which really hit me because he's an extraordinary artist. He's now well and is his 90s. And I think it's when we hear about famous people, Glen Campbell was another I was lucky enough to interview Glen Campbell after I was diagnosed with Alzheimer's. And it was a remarkable day. And I could very clearly see the effects of the disease. But he then went on to perform in a world tour.
Speaker 2
And as he said to me, his wife said to me at the time, and I think the same has said about Tony Bennett, there's something about the stimulation of the brain that music can achieve, that other aspects of our lives can't. But my point being that when we hear about these people that we've just lived with and grown up with and, you know, enjoyed their concerts over the years, it just brings it home to you once again, the the real scourge of this disease.
Speaker 1
Yeah. And to some extent, I mean, in the initial stage as individual is is aware that they're starting to have problems by often by the end stage. They may not be aware, but of course the family is impacted. So so it not only impacts the individual, but it impacts, you know, their and their entire family and their community of friends and and so forth. So I have a great aunt who has passed away a few years ago.
Speaker 1
She lived to ninety seven, but she was diagnosed with Alzheimer's and I don't know, like the last 10 years of her life. And you do see kind of snatches of lucidity, but it's very sad to see somebody who was so vibrant and vital succumb to this disease. That's really a horrible disorder.
Speaker 2
It is tough. Julie, thank you so much. Really enjoyed talking. Yeah, well, thank you for having me. Yeah, this has been great.
Speaker 2
Thank you so much. And if you'd like to read more about Dr Anderson's work and more generally about the Book Institute, I'll put some details into the show notes for this episode. You'll find them at the Live Long and Mosta Ageing website at Slama podcast, dotcom, AMA podcast, Dotcom. And in fact, if you go to our indexed search for Episode six, that's where I talk to Dr Eric Verdin, the book's president and chief executive. It was one of our early episodes, but it's still very relevant today.
Speaker 2
This episode of the podcast was brought to you in association with Amazon to with LifeScience Company, which is pioneering, cutting edge, clinically validated coeliac nutrition under its timeline brand. The podcast is a health sponsored media production. If you enjoy what we do, you can write and reviewers at Apple podcasts. You can follow us on social media at Larmer podcast and direct message me at the Post. Many thanks for listening.

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These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease. References: *Nutrition studies: 500mg Mitopure® have been shown to (1) induce gene expression related to mitochondria function and metabolism and (2) increase the strength of the hamstring leg muscle in measures of knee extension and flexion in overweight 40-65 year olds. Data from two randomized double-blind placebo-controlled human clinical trials. **Nutrition NOURISH Study: 500mg Mitopure® have been shown to deliver at least 6 times higher Urolithin A plasma levels over 24 hours (area under the curve) than 8 ounces (240ml) of pomegranate juice in a randomized human clinical trial.

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