Feel Better, Live More with Dr Rangan Chatterjee - #44 How to Grow New Brain Cells with Dr Sandrine Thuret

Episode Date: January 9, 2019

Can adults grow new neurons? Until relatively recently, experts believed the answer was no. But neuroscientist, Sandrine Thuret explains why she believes humans can indeed generate new brain cells, a process called neurogenesis. She discusses the findings of the fascinating research in this area and gives practical advice on how we can help our brains better perform neurogenesis through our lifestyles- improving mood, increasing memory formation and preventing the decline associated with ageing along the way. This is an empowering and eye-opening conversation – I hope you enjoy it! Show notes available at drchatterjee.com/sandrine Follow me on instagram.com/drchatterjee/ Follow me on facebook.com/DrChatterjee/ Follow me on twitter.com/drchatterjeeuk DISCLAIMER: The content in the podcast and on this webpage is not intended to constitute or be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your doctor or other qualified health care provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have heard on the podcast or on my website. Hosted on Acast. See acast.com/privacy for more information.

I think it's important that people are aware that, as you said, you know, all this lifestyle, you know, do not impact just exactly how you look, maybe. You know, a lot of people will do that for that. But actually, how you can preserve your cognition or even your happiness, we could go that far, you know, to prevent, you know, depression. are, you know, to prevent, you know, depression. Hi, my name is Dr. Rangan Chatterjee, medical doctor, author of The Four Pillar Plan, and television presenter. I believe that all of us have the ability to feel better than we currently do. But getting healthy has become far too complicated. With this podcast, I aim to simplify it. I'm going to be having conversations with some of the most interesting and exciting people both within as well as outside the health space to hopefully inspire you as well as empower you with simple tips that you can put into practice immediately to transform the way

that you feel. I believe that when we are healthier we are happier because when we feel better, we live more. Hello and welcome to episode 44 of my Feel Better Live More podcast. My name is Rangan Chatterjee and I am your host. Now, as a practicing doctor, low energy is one of the commonest complaints that I see in my practice. For that reason, I have created a free six-part video series to help you increase your energy so that you can get more out of life. If you would like to watch these videos, you can sign up to receive them at drchatterjee.com forward slash energy. Today's episode is a fascinating conversation with one of the world's leading brain health scientists, Dr. Santrine Touré. Dr. Touré is head of the Neurogenesis and Mental Health Laboratory at King's College London. She's also editor for the journal Nutrition and Healthy Aging and associate editor for the Journal of Alzheimer's Disease.

for the Journal of Alzheimer's Disease. Her research lab is exploring the various mechanisms that control the production of new nerve cells in the adult brain and how this impacts our mood and our memory. Sandhri's research is incredible and in today's podcast she gives us a masterclass in brain health. We discuss what exact lifestyle factors we can engage in to promote the growth of new nerve cells in our brain. We cover a wide variety of areas, including diet, sleep, physical activity, as well as how having sex can impact this process. I really enjoyed this conversation and I'm sure that you will too. Before we get started, I do need to give a very quick shout out to our sponsors who are essential in order for me to be able to put out weekly podcast episodes like this one. Athletic Greens continue their support of my podcast. There's no question that

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live more. Now, on to today's conversation. So Sontreen, thank you so much for joining me on my podcast today. My pleasure. So I'm running a bit late, but we managed to get here, get everything set up. And, you know, I first came across you, I think, with your TED Talk, which is doing phenomenally well. It's got over 6 million views. And you talk about something called neurogenesis. Now, I wonder if you might explain what neurogenesis is for me, but more importantly, for my listeners. Yeah, of course. So neurogenesis by definition is a production or the birth of new neurons. And what has been found is that obviously as we are developing, there is a lot of new neurons that are being generated in the brain of the fetus. And then as we are born, it was thought that this production of new neurons would stop. as we are born, it was thought that this production of new neurons would stop.

So basically the brain is formed and this is it. Nothing, you know, will happen anymore. The worst to come is actually we are going to, you know, lose some neurons, but then no more new neuron will be made. And then it was then discovered in the mid-60s by Altman and Das that in a rat brain, actually, they did detect neurogenesis in the adult brain, but in a very restricted area, which is called the hippocampus. Wow. I think people have heard of the hippocampus. It's commonly known as the memory center of the brain. It's probably a little bit overly simplistic, I imagine, and maybe you can shed some light on that. But I just want to sort of touch on something you just mentioned, which is when I was at medical

school, and I went to medical school between 1995 and 2001, I'm almost certain that we were taught that once the brain has stopped developing, no new nerve cells or neurons can be produced. That was it. It was static. And what you're saying and what your research is showing is this may not be the case. Yeah, that's correct. So I believe that there are still many places, many medical schools that indeed, you know, just give this simplistic view that once the brain has finished developing,

we can't make new neurons. And this is a big statement from Karl, one of our peers and father of neuroscience, that says, you know, everything may die, nothing may be regenerated. But, you know, unfortunately, it was proven wrong. And then this study I mentioned from Altman and Das, who were at the MIT in the US, where they showed that, no, look, in this rat brain, there are new neurons that are produced in the hipp where they showed that no look in this rat brain there is there are new neurons that are produced in the hippocampus but their study was pretty much ignored so that's probably why you

know that didn't take up but in the field we have to acknowledge them because there was the first one you know publishing a paper showing that and that was in the 1960s yeah in the 60s exactly and then in the 1990s where we develop developed new tools, new biological tools, where we can say, you know, we can basically tag stem cells. And if these stem cells are becoming neurons, then we will be able to detect them. And then using this new technique, then loads of people will say, no, this is true. These new neurons born in the adult brain of mice and rats. But what was very interesting is that it was not everywhere, all over the brain.

These new neurons are generating in the adult mammalian brain, only in the hippocampus. And in the rodent specifically as well in the olfactory bulb, so for the sense of smell. In the human brain, we know it's happening in the olfactory bulb, so for the sense of smell. In the human brain, we know it's happening in the hippocampus only. It doesn't seem to be happening in the olfactory bulb, which a little bit maybe makes sense because we don't use olfactory senses as much as rodents. But it is there. It is now shown quite robustly that neurogenesis is happening in the human brain in the adult human brain but very specifically in this maybe free-lage area which is the hippocampus yeah i mean super

interesting stuff i mean really in many ways a paradigm shift it's you know from from once our brain is developed and that's it we've got all the neurons and nerve cells that we are going to have all we can possibly hope for is to slow down the rate of decline. What this research is showing us that, hey, there might be things that we can do to help encourage the growth of new nerve cells, which is really empowering, actually. And we'll get to that in this conversation for sure. But you mentioned in rodents that they also get neurogenesis in the olfactory bulb. I'm not sure this is related or not, but we know that in humans, when we lose our sense of smell,

it can be an early sign of brain dysfunction or an early sign that we're going to develop dementia. Is there any relation there at all, do you think? So probably in animal model of Alzheimer's disease, indeed it is shown, as you rightly said, that they lose their sense of their early. And this mimics what we see as well in the patient. But we don't think that this has a relation with neurogenesis because it seems that in the human brain, even if we have neurogenesis, it's to undetectable level so it might be that we have a little bit but it's not something that we can see or we can modulate to a great extent as opposed to to the rodent so it's probably via different mechanism or it's an you know unrelated instance that where you know patient indeed lose a sense of smell this is not because they are losing newborn neurons they they might be you

basically losing olfactory neurons but it's not that they cannot make new ones the reason they are losing the sense of smell so we think it's it is something that's probably separated yeah now your research is showing that we are able to grow new neurons in the hippocampus. Can we do that in any other part of the brain? So, no. I mean, from the human perspective, it seems to be very restricted to the hippocampus. There's potentially a small area,

not too far, not to go into big detail, there's potentially a small area not too far from the hippocampus where maybe there is neurogenesis, but it has to be confirmed by further data. So this one group that I showed, you know, maybe this is happening here, and maybe these neurons are going to migrate to the striatum where we have dopaminergic neurons, but we would like a little bit more studies about that, and we don't know too much yet about this area.

What we know is that what's happening in the hippocampus that we can make you know approximately or it's an estimate 700 new neurons in the hippocampus on each hippocampus per day which you can say is quite little compared to you know the billions we have but they have a specific function, even though with these small numbers, they can have a specific function. So what is the function of the hippocampus? So the hippocampus as a whole, independent of whether you have new neurons produced as an adult or not, as you said rightly at the start, is that it's important for learning and memory, but also the ventral part of the hippocampus is important as well for mood and memory, but also, so, you know, the hippocampus, the ventral part of the

hippocampus is important as well for mood and emotion. So the dorsal part, the upper part would be important for learning and memory and the dorsal part for mood and emotion. So does that mean then that if we can engage in practices and, or we can sort of apply interventions that help neurogenesis in the hippocampus then potentially we might be able to impact our own learning memory mood and emotions yeah correctly so we have a lot of um that's incredible isn't it yeah yeah no it is it is quite incredible i mean we know so basically the basic experiment you know that a scientist would do to see that okay what is the functionality of these new neurons? What are they for? So basically what you do is that let's block the

process of neurogenesis in an animal model, in mice, we block it. And then we see, can this mice still be, will this mouse still be able to learn? And then what we could see is that if you block neurogenesis, then the mice lose certain abilities specific ability of learning and memory specifically spatial learning so how to uh orientate yourself in a space and find your way so this if you block neurogenesis then you block the spatial learning ability and um and you block as well as the retrie of these memories. So this is one aspect that was shown, you know, quite, you know, probably like 15, 20 years ago. And then more recently, what we have shown as well is that these new neurons, if you block them, you prevent pattern separation. And pattern separation is the ability to distinguish between very similar memories.

is the ability to distinguish between very similar memories. So, for example, well, this morning you came, you were looking for your batteries or the memory card, and you know you have them in the bag and probably use it a lot, but maybe, you know, once you put it, you know, in the front pocket and then some days you put it in the middle pocket and sometimes on the front pocket and then some days you put it in the middle pocket and sometimes on the side pocket. So the ability to remember that it's something very similar.

So the pattern separation is distinguishing between very similar memories. So now you have to decide, did I put it in the front pocket or in the back pocket? So it's a spatial orientation of similar memory or like where you are going to um put your you know travel card when you come home at night you know on the side table on the main table so this kind of spatial very similar memory so these neurons are important for that well what's interesting about that is you're saying when you block neurogenesis so let's say we've got you know x amount of neurons in our hippocampus and if we assume that they're functioning well neurogenesis is the formation or the the creation of new nerve cells is that fair to say yeah absolutely so you're blocking the

creation of new nerve cells and that is already having an impact on people's ability to learn and their memory yes so that makes you think so do the existing nerve cells almost require neurogenesis to actually you know do their job you know is neurogenesis because because those cells are still there right yet blocking neurogenesis is affecting its ability to function so to me it seems as though there may be some, I don't know, some synergistic benefit of them and they're both happening. Absolutely. I mean, I was not expecting to go into so much detail,

but you are exactly onto what we think is happening. Because how can so few cells have such a big impact? Well, the only way they can do that is because they are connected with the rest of the circuitry. So it's not that you make new nerve cells and they are just hanging around loosely. No, when they are born, they are going to have immediately, from very early on, they are going to have an important role because they are more excitable. So these young cells are more excitable than the old one.

So this is one of the reasons that they have this specific role. But also as they mature, so they are going to survive and mature, they are going to connect to the rest of the circuitry of the hippocampus and the rest of the brain. So this is why we think they have, you know, so little cells can have a big impact. And they are very important indeed to have a functional, you know functional spatial memory or pattern separation or even have an impact on mood and emotion. This is incredible really. The more you learn about the human body, the more you find how very few things work in isolation. Obviously scientists like to isolate things

so they can study what they're doing. But you're finding, you know, as in many fields or so, those new nerve cells are actually connected to the other nerve cells and they're connected to other functions of the brain. And it never ceases to amaze me how interconnected the body is. What helps to promote neurogenesis and what helps to, what's the opposite, sort of decline it or switch it off? What are the good things basically and what are the bad things? So as you said, studying the brain is in isolation. Like many of us do exactly to refine specific mechanisms, cellular and molecular mechanisms. I think at this time, and this is a big trend

where people are studying the mind and body, you know, alignment, and neurogenesis is a perfect example to illustrate that, that, you know, what you do every day actually impacts the production of these new neurons. So we can start with the bad things maybe. You know, like we know that stress is going to decrease the number of new neuron produce in the hippocampus. And then as a consequence, depression when we induce stress, decrease neurogenesis, and then look at the behavior of the animal after.

So this is one where this has a big impact. If you stress a mice, for example, even if it's just chronic mild stress, so little stress but every day, then we will decrease stress but every day then we will decrease neurogenesis and then we will see uh similar behavior to what human would describe as as depression so this is one i mean this is i mean you're showing a direct mechanism by which stress can impact mental health by which stress can affect our ability to remember things it's a direct mechanism there isn't it because there's lots of theories behind this and um you know i've locked myself away for the last

few months writing a new book on stress and you know when i cover this a little bit in the book and i also cover this when i'm teaching doctors on our prescribing lifestyle medicine course so that's it's a little a little bit of stress can be a good thing. A little bit of cortisol can help your brain to function better. But you just mentioned that. The chronic mild stress is a bad one. Yes. Yeah. So the chronic mild stress is the one that we know is going to decrease neurogenesis. Do you see that, as a GP, I'm seeing lots of people now at a much earlier age, maybe sometimes in their 40s, coming to talk to me that they just can't quite remember as well as they used to. And I can't help but think that, you know, the way we're living our lifestyles now, you know, where we

have very little downtime, we're constantly filling our brains with new information. We're, you know, we're waking up, we're straight onto our phones, on our emails, we're, you know, we're standing in a queue in a coffee shop. And instead of just taking it in, we're trying to catch up with everything. I just wonder how much of this might be impacting neurogenesis, which might be causing, you know, digital induced early memory loss for want of a better term. No, no, that's a good point. I mean, we can't say for sure because, I mean, what we have to say is that we can't measure live neurogenesis in human.

We can only do post-mortem studies or we can use proxy as we do in the lab. So it's difficult to say, you know, to set up an experiment and say, okay, we have a group of people, you know, being constantly on their phone, you know, being stressed. And then we have other people that maybe, you know, take it easier and say, for sure, we have a decreased neurogenesis, but, you know, the clinical outcome is there, you're right. And then our mouse study showing that, you know, chronic mild stress induce a decreased neurogenesis. When we link both, you could clearly argue that potentially neurogenesis is a mechanism by which this chronic mild stress is going to induce maybe a slight memory decline or cognitive decline.

And there is a strong link in mood and emotion and memory performance. So in patients with depression, it's quite new, but clinicians never looked before, but actually these patients are not just depressed, they also complain with some memory loss or that they are not as sharp as they used to be. So there is a clear link between there, and in the lab we do think, and not only me,

but the rest of researchers on neurogenesis, things that there's a strong link on cognition and mood and neurogenesis is really where everything is happening as an adult in the hippocampus yeah it really is incredible um so you know stress i mean it's really quite striking what you're saying that chronic, even a little bit of chronic daily stress might be enough to impair neurogenesis, which is, as you've already explained, is so important for so many functions of our brain. So that's one thing we need to be careful of. What else impacts neurogenesis? So, I mean, when nothing we can do much about it, but as we get older, we still have neurogenesis, but it will go down, basically.

So this is what has been observed as well in rodents. This is what, as well, we estimate in humans. As we get older, we have a lower level of neurogenesis. So it is still happening, and you can still stimulate it and increase it, but naturally, it will go down, which might explain why as we get older, maybe our pattern separation is not that good. And this has been shown by many people around the world where you have pattern separation tasks where you ask, you know, people to recognize, is this a new object, an old object, or have you seen before? So this is how we can measure that. We can see that with age, naturally, people are not as good with that.

And then, because obviously the population is very heterogeneous, as you get older, young people will perform really well, whatever is their background or their education or their lifestyle, like if they exercise or eat, whatever, they will perform really well. But as you get older, this is where you see the difference. So where you see that you have older people who perform as good as young people, and then you look back at their lifestyle and you say, well, these are the ones exercising, these are the ones eating well, or have a higher level of education.

And then you have people that perform as the average old, and then you have the old, old that perform really much worse than they should be. So age is a big, has a big impact on neurogenesis. So I guess the question then is, well, we're going to reduce our rates of neurogenesis as we get older, because that's what happens to all of us. So is there anything we can do to slow that down so what we know from uh from quite a few studies so some of my colleagues in the u.s actually my my mentor gage from the salk institute professor gage um was the first one to show that you can modulate neurogenesis uh by the environment so it is something that you can modulate neurogenesis by the environment.

So it is something that you can change. And the first experiment they did was actually showing that running in mice will increase neurogenesis. So you have these beautiful studies where you show that if you leave a running wheel in a mouse cage, you know, just free to access access the mice actually love to run so they will start running and you have your control mice where they you know they will have a cage without a running wheel and then when you look at their neurogenesis after you have an increase of 30 percent 30 so yeah this is quite huge and then what you see is that you can do that in the young animal but then as the animal gets older you know you can increase it further so basically

you know it's more efficient if you have you know if you have a lower neurogenesis running will increase it even more than if you have already a good neurogenesis so running exercise seems to be a good a good uh trigger of increasing neurogenesis so so running uh lowering stress levels would clearly be a good thing um i think on your TED talk, you mentioned sleep as well. Is that right? Yeah. So sleep is an important one where there are quite a few studies there that really nicely aligned that, you know, if you sleep deprive mice, you will have a massive decrease in neurogenesis. And it's not just small, you will have a big decrease in neurogenesis and it's not just small you will have a big decrease maybe of 50 percent so and here we are talking about not maybe massively sleep depriving so not depriving them from sleeping at all but disturbing their sleep

maybe even just fragmenting their sleep will decrease neurogenesis so there is a big uh there is a big impact uh of sleep deprivation on neurogenesis yeah i there is a big, uh, there is a big impact, uh, of sleep deprivation on neurogenesis. Yeah. I mean, it's, do you know what's fascinating for me, Sandrine, is that, you know, I'm very keen to promote that it's important we look after our lifestyles and that, you know, I, I'm in my years of practice, I've seen, four, what I consider to be the four of the most important areas that have the most impact on our health, but also we've got a fair degree of control over. It's been food, movement, but equally important sleep and relaxation. And what's incredible is that you're one of the, you know, arguably the UK's leading researcher, but certainly one of the world's leading researchers in this field. And it looks as though that those lifestyle factors that I talk about are not just relevant for our physical health and, you know, whether we've, you know,

whether we maintain a healthy weight or not, but potentially are directly impacting our hippocampus and our ability to create new nerve cells. It's amazing because I think people often feel that, oh yeah, good diet, a bit of exercise, sleep. Yeah, you know, these things are important, but you know, where's the hard science? Where's, you know, it's almost like too obvious, but it really helps show that your research is showing that these things are so important for human beings to maintain health as we get older i find it remarkable yeah no i mean i think it's important that people are aware that as you said you know all this um lifestyle you know do not impact just exactly how you look, maybe, you know, a lot

of people will do that for that, but actually how you can preserve, uh, your cognition or even your happiness. We could go that far, you know, to prevent, uh, you know, depression. Um, so I think the hard science from our lab, you know, I mean, obviously this is all rodent study where you are going to give a bad diet to a mice, high saturated fat diet, and then you will decrease their neurogenesis. I mean, you know, these are, you know, the same mice. You cannot argue that, you know, because when you look at epidemiological study

where you see that, oh, people who are doing the Mediterranean diet versus another diet are living longer, better. They have a lower onset of Alzheimer's disease. They stay cognitively healthy longer. So we have all this nice data that already should convince the people, right? Sure. But on top of that, if you just give, you know, a Mediterranean diet like, you know, to a mice versus something which is really high fat, then you will, you know, forget

even about the behavior, but we'll see the same behavior. They will be cognitively sharper if they follow a good diet as opposed to the high fat diet. But then if we look at their brain, you physically see that they have less of this newborn neuron that are made when they eat a high fat diet. So really that's quite convincing.

No one will argue, well, it's because maybe the people doing the Mediterranean diet are living next to the seaside and they are just happier. And I said, yeah, I, you know, it might be a compound that, you know, add on to that. Uh, but if you look at the lab, you know, we have hard data showing that, look, these mice are in the same cage. is super controlled studies we just change the diet we even have the same genetic background we are not even talking about you know different genetic background and some people are luckier than others here same genetic background we just change the diet and then we can modulate the production of these new neurons yeah i mean that's incredible that diet directly will affect neurogenesis I know a lot of people listening to this will want clarification

on the fact that, you know, when we're, and obviously you are a researcher in the field, but my understanding of when we're feeding rats and rodents high fat diets, what we're talking about is a chow mixture that's sort of high fat and high in sugar high in sucrose is that right so yeah it's a sort of very in many ways reflective of um the western diet in in many ways unfortunately yes as opposed to let's say somebody who was eating a mediterranean diet which is rich in um avocados and olives and nuts things which are also high in fat so i i just think which i'm keen to clarify that it's absolutely a toxic high fat and high sugar diet yes you're talking about in the lab yeah yeah absolutely yeah

yeah in the lab it's saturated uh you know uh fat as opposed to you know uh other type of fat but is it with sugar as well so it depends there are different type of experiments some people just focus on the high fat diet some people people actually have done high sugar, which is equally bad. And there are some mix where you say we call it the cafeteria diet for the rats, which is high fat, high sugar, which is equally worse. But what we have tried to do is that, and what we are doing now at the moment with the big European consortiums, we're working with people in Spain, France, Holland, Austria, Germany, all together, is trying to say, okay, we have these animal studies, which people say, well, how does it relate to me? Although, yes, I'm convinced that, you know, in isolation, that works. So, you know, potentially diet has an impact. But how,

you know, are you sure it is the same in humans so what we are doing now is that because i told you we can't measure neurogenesis in living human so we are trying to find proxy so how could we do that and what we are doing is that we have some um people uh all over europe who are uh following um like a mediterranean like that so high in olive oil fish vegetables colorful you know fruits and then and then we have people that you know eat a more you know western diet you know maybe not not not so much of this fish intake and vegetables and then they have been followed already for 15 years and they were recruited when they were probably around their 50s and they were followed by some of our clinicians and what we do is that we measure their cognitive abilities so we see that some

you know stay stable with their cognition and some will so show basically a slope they will have a slow cognitive decline, which is sometimes average. So what has been shown already is that the people with the Mediterranean diet maintain their cognition better than the people who follow Western diet. So that was not. But what we wanted now to validate in the lab is that we take the blood of these people and what we do, we have developed an lab is that we take the blood of these people and what we do we have developed an assay where we have a cell line which is a cell line of human apocampal stem cells and then we put the blood of these people on the cells so it's their blood uh and we can you know

and we know all about these people we We know their genetic background. We know what they ate. And we know what are their cognitive scores. And now we are trying to see is that, you know, does their cognition and diet correlate with how much their blood is going to induce neurogenesis? So I agree this is not for sure what's happening in their brain, but by taking their blood, put it on stem cells that can make neurons or not, and we measure the percentage of these new neurons, then we'll be able to validate this rodent study in a human population.

So we already have some primary data from another study we run here in the UK, where we have people who do intermittent fasting, which we show that it improves their pattern separation. fasting which you know we show that it improves their pattern separation and if we take their blood on the cells we already know that it is promoting uh neurogenesis so so this this this sort of work you're doing on humans now is suggesting that intermittent fasting may well promote neurogenesis yeah yeah so this we had shown already in mice but now we wanted to show what's happening yeah yeah yeah so and can i may ask what you know what was the type of intermittent fasting is that you know what what were you actually you know because intermittent fasting can be called so many things these days what were you guys actually doing so what we wanted to

compare what was interesting is that in our mouse study, we did compare calorie restriction, so decreasing the calorie intake of the mice, let's say of 20%, versus intermittent fasting where we gave food every other day to the mice. Every other day. that either calorie restriction or intermittent fasting had a good effect on certain readout, but only intermittent fasting was improving neurogenesis in the mice, not the calorie restriction. It was very interesting. So then we wanted to see in humans what was happening. So we had a group doing calorie restriction and a group doing intermittent fasting so and for the human population the intermittent fasting was actually like the five two diet so meaning eating five days normally and only two days they would eat 600 uh kilocalories so like you know like three tiny small meal like you know the equivalent of three small cereal bar, but, you know, in a balance, in

a balanced way with protein and carbs and so on. And then what we could see is that contrary to our hypothesis, because this is science, we thought, oh yeah, surely we will see, you know, a difference only to the people doing intermittent fasting because that's what we saw in rodent. But no, in humans, the calorie restriction, you know, of, you know, every day. So basically every day the people ate a little bit less, had a similar effect than intermittent fasting. So we did see that both improved their pattern separation.

And then both as well in their blood, an increased level of, we call it the longevity hormone, Cloto. So both calorie restriction of like 20 to 30% and the intermittent fasting, so eating two days a week much less, so half or maybe a third less what you would eat every day, had a positive effect in the human population. Whereas in mice, we only saw a good effect of intermittent fasting. Yeah, it's fascinating, really fascinating. You know, what excites me is that it's what you know i talked to a lot of different researchers on this podcast um i spoke to um professor sachin panda from yeah so institute

yeah we had a phenomenal conversation about his research on time-restricted eating and he was showing again he like you started off with rat studies and they're now moving over to trying to replicate this in humans and it's remarkable the sort of benefits that they are showing whether it be improved blood sugar control improved immune system function uh losing weight maybe um increased endurance for athletes you know it's uncanny that how many different researchers are saying a very similar thing, which is, I think it's safe to say we're not designed to eat food all the time from the minute we wake up to the minute we go to sleep, seven days a week, 365 days a year. It doesn't matter what research you talk to about what function in the body they're looking for, reducing how much we eat and having sort of some set periods of time with either low calorie intake or not eating seems to have multiple benefits on the body.

Yeah, I mean, I think you're right. There are loads of studies. One of the leading researchers as well is Matt Madsen, who was the first one trying to promote exactly this concept of intermittent fasting or energy restriction or indeed having a certain amount of time in between meals as opposed just to calorie restriction. And one of the things I recommend people to do based upon the research that I've read and what I've seen in my practice is, you know, 12 hours in every 24 hours where we don't eat, I think is, I'm sure you can get more benefit if you go more aggressive than that. But I think that's, you know, eating for all your food within 12 hours each day seems like a reasonable, achievable recommendation for most of us absolutely and sorry you were saying about this this research no no no i was saying yeah i mean i i agree with you i think in our in our trial that's what we did when the patient the participant were under the intermittent fasting diet we're telling them please eat your 600 kilo calorie within you know

a certain time so that you can be at least 16 hours. We were asking them 16 hours without eating, so twice a week, which is not a big ask, to be honest. It's quite doable. And then again, if you look back at rodent studies, and this is an interesting conclusion that you can take, is that, for example, in animal model of Alzheimer's disease, not example in animal model of alzheimer's disease not just one animal model of alzheimer's disease but plenty if you put this mice under calorie

restriction and the way they do in animal research often they just do intermittent fasting so they leave them indeed uh you know at least probably 16 to 20 hours without food is that you could cure alzheimer's disease just by putting this animal under intermittent fasting. And it's just that, you know, I mean, that, that would be incredible. So the idea is that people are not so keen on, you know, the idea of intermittent fasting and, and then you understand that. So, you know, what could you do? What can you find? I mean, it would be so easy to tell people, you know, be reasonable and, you know, please go, you know, twice, twice, twice a week, you know, reduce your food intake in content and in, you know, restricted in time, you know,

will increase definitely neurogenesis, that's for sure, but has a lot more benefit. So now are people ready to do that it's difficult so that's why in the lab we are trying to understand the molecular mechanism that's behind it so we are really trying to say now we have our study where people go under intermittent fasting they do better at memory task they have increased this longevity hormone cloto you know so basically what we are trying to understand is that how does this happen? How does this work? So that we can refine the pathways where we have something to play with. Yeah, it's incredible, isn't it? So you're saying to avoid the sort of typical

Western diets, the sort of high sugar combo diet that we often see in the West, have periods of time where we are reducing our calorie intake or do some sort of time-restricted eating may be beneficial for neurogenesis. Are there particular foods that you've found that are really helpful for neurogenesis? Yeah, so not just my lab, there are plenty of other labs that have shown, for example, Yeah, so not just my lab, there are plenty of other labs that have shown, for example, flavonoids, which are contained in fruits with dark skin, like blueberries. I'm getting some pictures on the wall. Or even strawberries.

So lots of dark skin fruit, grapes, will have high flavonoid contents. And we know that flavonoid will increase neurogenesis. And there are studies in human where, by a colleague in Reading University, not too far from here, where they gave actually blueberry juice to participants and they showed that it improves their memory and it improves the blood flow to the brain. So it might be one way, you know, improving blood flow. So for example, if this flavonoid improves blood flow and potentially if you have improved blood flow because the hippocampus is nicely vascularized,

you know, you have more factors that reach this area that might stimulate the production of new neurons. I mean, that is incredible, isn't it? You're saying that blueberry juice can increase blood flow in the brain. Yeah, that's nicely shown by my Jeremy Spencer in radio. I think this just goes to show how much we need to expand out the conversation on food. It's so much more than just energy for the body. It's information.

It's blood flow to the brain. Incredible. much more than you know just energy for the body it's it's information it's it's um you know blood flows to the brain incredible and the is that obviously blueberries contain flavonoids but so does i think dark chocolate does as well yeah dark chocolate as well has flavonoids although because i got this question as so many times so once i did the calculation how much chocolate do you need to eat to have, to increase your blood flow? Let's say it'll be too much. It'll be too much.

Then you would have a huge high fat content or you would have to eat like so bitter chocolate, like a hundred percent chocolate. I don't know if you had tried already. It's extremely bitter and you would need to eat probably 400 grams of that. Oh wow. So a high calorie intake. So probably blueberry might be might be the best way although some people might be hearing this again oh i fancy the challenge of 400 grams a day

but isn't that interesting that that sort of reminds me a little bit about some of the studies on wine and resveratrol because um and again i'd love to know what happens with resveratrol on neurogenesis but certainly some of the studies i've read about the you know the reported beneficial effects of red wine and trying to try to tie that out to resveratrol they're sort of suggesting that actually the amount of red wine you would have to drink to get the amount of resveratrol that the studies are showing is you know quite a remarkable amount um so you know i guess i guess that leads on to the question what does alcohol do to neurogenesis so alcohol itself so if you you know if you just use pure ethanol on on uh on cells basically or if you do an in vitro experiment

let's you know we can leave rodent you know away poor guys uh a little bit but if we take human cells in a dish human apocampal cells that can make new neurons or not and then you add you will add ethanol basically you will kill it but then if you add some resveratrol you know that mediates you know uh the cell death let's say so you know so resveratrol will have an impact indeed. And as you said, you know, the amount of resveratrol you would proportionally need to drink from wine would be huge. So I think the conclusion of, you know, this discussion is really just about balance. You know, maybe you don't eat 400 grams of chocolate and drink 10 liters of wine, but, you know, maybe eat less. We'll have, you know, eating 30% calorie intake less or doing intermittent fasting will have the same effect, you know maybe eat a little less we'll have you know eating 30 calorie intake less or doing

intermittent fasting will have the same effect you know as that but if you want to do it really nicely you know eat a little bit of you know um you know fruit uh yeah red wine if you like you know uh wine is is better than white wine that's for sure because of the skin of the grape is there and the skin of the grape is there. The skin of the grape is the one containing the resveratrol. So you will have no resveratrol in white wine, for example. Okay, that's interesting. So it's only in the red wine because of the skins.

And where were you born, Sandrine, can I ask? Oh, in Burgundy. In Burgundy. I'm not promoting Burgundy wine. Is there any… I mean, I'm just saying, I wonder if there's any sort of cultural bias creeping in here to the recommendation of red wine. Probably not. We have beautiful white wine in Burgundy, actually. Do you?

Yeah, and red wine as well. But to be fair, okay, what I can say now so that I'm not, you know, being told I'm biased is that... I'm only teasing, by the way. But people have measured the level of resveratrol in different red wines. And Burgundy wine are not the one with the highest level of resveratrol. Actually, Bordeaux wine have a higher level of resveratrol

compared to Burgundy wine. We don't know exactly why, because resveratrol is produced as a defense mechanism, you know, with fungus by by the grape so it is um you know it could be it's it's a question of climate and and probably of the strain of the grape as well so it's a mix but yeah so border wine has a little bit more residential about burgundy wine it it hurts me to say that but it's a reality but it's good to know that's a good tip for people um what about

omega-3s which we hear a lot about in the context of brain health yeah so omega-3 fatty acids there are lots of study on that showing that how omega-3 fatty acids are you know in rodent model that are good for cognition and especially there are loads of study that have shown that they are also protecting for depression. And there are even some patient data where they did a clinical trial where they supplement the diet of the patient, not directly by fish, by supplements, so DHA and EPA, and one milligram of it,

which is what you probably commonly find in health stores. And then they show that it had a comparable effect to Prozac for some patients. And that's a supplement? That's as a supplement. So this study was quite impressive, but we have to take it very carefully because, you know, the severity of the depression of the patient in this study maybe was quite low and it might not be relevant to you know all the patients and people shouldn't stop taking antidepressant and take you know omega-3 fatty

acid supplement uh but what people have to be aware of is that when you buy your supplement you know watch the label because you want epa and dha you don't want the other like ALA which are not being carried to the brain. So they will not do anything. And some of the cheaper supplements actually are full of the ALA. So you want EPA and DHA. I think it's a really important point that, isn't it? And particularly I think for a lot of people are choosing to have vegan diets these days. Yeah, that's tricky. Yes, yes. Well, because a lot of those sources of omega-3 contain ALA.

Yeah, exactly. And you're saying that the brain can't use ALA, is that right? So you can derive from ALA, you can make EPA and DHA, but we are super inefficient. We are very inefficient. So you would have to eat kilos of ALA to make one milligram of EPA or DHA. So whereas you can have, you know, the EPA or DHA you need by eating 80 gram of salmon, for example.

Yeah. So which is, you know, but I understand for people who are vegetarian and vegan, you have to go other ways. And I think there are some new products that are algae that are actually containing EPA and DHA. Yeah, I read that as well actually. So that's one way vegan and vegetarian people can get their proper amount of omega-3 fatty acids that are relevant to brain health. Yeah. And I think, you know, any brain researcher who I've had on this podcast, including Dr. Lisa Moscone, who wrote the book Brain Foods, you know, most of them, including yourself, are probably sort of would recommend fatty fish because of the science of

the research and showing what it can do for our brain. But as you say, you know, we've got to be very respectful of people who are choosing not to do that. And what are those other methods where they can also get some of those benefits off the omega-3s. I just want to go back to exercise for a minute. Because you mentioned running as specifically being able to increase rates of neurogenesis. Do we know what other forms of exercise can do or is it specific to running or do we not know yet we don't know yet i think i think it would be really an interesting question you know to see what we know from my study is that if you let them freely running you will have an increased neurogenesis however if you force them to run, you will not see it. So these are

some kind of things we have to be aware from rodent study. In humans, we don't know if it's going to be the same, but, you know, likely, is that probably there is an idea of maybe, you know, exercising with pleasure or really wanting to exercise you know maybe to have the full benefit because if you force the mice you know to run as opposed to just let them run when they want then you don't see such an effect so there is probably you know to be honest some kind of you know mitigating effect with you know are you forced to exercise or do you want to exercise so we have to be aware of it yeah that's really interesting and i guess yeah we are speculating on humans but it it would seem reasonable to recommend to people to do the form of exercise that appeals to them

because a they're more likely to stick to it anyway but yeah it you know if you're someone who hates running yet you've heard this podcast and said oh you know this this expert in neurogenesis says that running is going to increase the growth of my nerve cells well who wouldn't want that so they're going to start going running every day but maybe they're going to hate it as they're doing it i guess this is raising questions which hopefully a research paper will answer at some point yeah no maybe the benefit will be limited i i i mean from extrapolating from the mouse study i think if people are forced to do an exercise they don't like i don't think they will have as a great benefit so i think yes i mean i i'm a runner so i like running so it's convenient for me but one of my you know i, my kids are still young, but I encourage them, you know,

to have a healthy lifestyle. At one point they were into running and now they hate it. So I'm not going to force them to run because I can see that, you know, it makes them miserable. But they found other ways to enjoy, you know, namely running after a ball, which is still running, but that's a different concept. And I know talking to a lot of people who really do not like running, but actually they do a lot of running without knowing it. You know, when you play, you know, any sports ball, you run after a ball.

Of course. So I think we shouldn't generalize it has to be running on the road or on a treadmill and, you know, do nothing else. No. I mean, as long as you increase, for me, potentially, you know, it's all about increasing the blood flow to the brain uh very likely so you know any type of exercise where you are going to achieve that should be beneficial when i was researching um your work online there's two things that also came up that we've not spoken about today one of them is soft food and i found that really

interesting um could you could you could you explain a little bit about how soft food might impact neurogenesis so this comes from uh loads of japanese groups so all this research has been done in japan because i think they are very uh interested in food textures. And then what they have started to show, again, these are rodent studies, is that if you give soft food to the mice, so as opposed to you are describing the chow, so which is crunchy, so it's like little what you give maybe sometimes to your cat. So this is what we give to the rodent. So it's crunchy and we have to chew on it. And then they decided, OK, let's see if we put that, you know, mash it, put it in

water. So it's kind of a liquid diet. So it's amazing. The paper show that if you put a mice, you know, from their normal crunchy food to a liquid diet, the neurogenesis rate goes down like a 30%, which is huge. And then they said, okay, you know, what could that be? So they did a bit some kind of maybe more barbaric experiment where they removed the teeth of the mice, you know, and still giving them the hard food somehow or softer food, but they couldn't chew really. So the idea is that, you know, probably chewing is, or mastication is what will induce

neurogenesis. So now there are different hypotheses. It could be that indeed, again, we increase the blood flow to the brain, or we have some direct, we have some direct nerve cells that actually, you know, could be responsible. So again, it looks like, you know, it's not just food content, uh, or calorie intake, uh, but also food texture might have an impact on neurogenesis. And we think it's important. You know, it might sound kind of a funny topic, like, oh, food texture, come on, sorry. No, but think about people that are getting older.

Often they will be given in retirement, they just get soup because, you know. Puree, soft food you know, exactly, because maybe indeed they have some dental problem. So maintaining a healthy, you know, teeth is very important for the old age because you will be able to continue chewing. This is blowing my mind, Sandrine. It really is because it's, it's the more you, you look at the body, the more you see how everything is connected. You can't even just look at necessarily the food in isolation it's how much of that food it's when you eat that food it's what's the texture of that food um and you know we know oral health is is critical for systemic health we know that um you know having gum disease will increase your rates of cardiovascular disease

and stroke so we sort of know that don't we from the science that actually the health of the mouth the health of the teeth is important for the health of the rest of your body and it's just you know all these little studies that help teasing out some or you know helping us to hypothesize various mechanisms by which that might might be playing out it's really i find it so fascinating really really interesting okay so um a lot of this stuff is the sort of thing i guess that 100 200 years ago people would be eating um sort of real food that required mastication to chew it and i guess now we've got a tendency i'm sort of thinking as i go through this, but we're in juice culture and smoothie culture. Could there be a potential disadvantage from slurping our food down without having to chew it? I mean, who knows?

I mean, yeah, exactly. Who knows? I mean, I think if you eat the least processed food, I think that's the best way to translate that. Basically, if you don't process the food, like we have an image of an apple here in front of us. So instead of to drink apple juice, you know, or even, you know, like if you, you know, have one of these fancy food processor where you get the whole apple, but, you know, in a smooth or, you know, drinkable, fresh juice. What's the advantage of eating a raw apple as opposed to an apple juice? Well, first, it will take you much longer to eat it. So you probably will feel satiated, as opposed to just ducking down your juice. Then if you drink juice, you lose all the fibers, right?

then if you drink juice, you lose all the fibers, right? And then now we can add, if we want, you know, to make this argument a little bit more compelling of mastication and chewing. Well, I mean, the apple is crunchy and you will chew on it and you will eat it as opposed to drink it. So I think, you know, if we want to summarize the whole thing and give, you know, an easy tip, it it's like don't eat your food too processed. And if you do that, you probably will do quite well. Yeah, I totally agree.

I'm actually staring at my apple juice there in the corner now and I might not have it anymore. But it's cold pressed, so you have the fibers at least in there. But you will drink it much faster than if you would eat an apple, right? No question. So that's the thing. How many apples are in there? Three, four apples maybe? Yeah, possibly.

It's pretty hard to eat three or four apples in a row. Yeah, exactly. It's pretty hard to do that. The final thing we've not discussed, which I think is of critical importance, is what does sex do to neurogenesis? Oh, yeah, okay. That's from your TED talk. Yeah, it is in the TED talk. So this is a study from, or some studies from Elizabeth Gould, where, you know, and when I was doing my postdoc in the US, I was with another postdoc, and we

always thought about doing this experiment, we should measure neurogenesis, you know, after mating of the rodent. And we never found the time to do it because we thought surely it's, you know, it's going to be, have a good effect. But then some other people did it. And then, yeah, I mean, either for male and female, so intercourse will increase neurogenesis. So again, you can say, you know, why and how we, you know, you know, again, you could think about, you know, is it a form of exercise? Maybe not for rodents, though, because they're much faster. But for humans, definitely. And then again, you have this idea of maybe having a good time, potentially. So yeah, so these are rodent studies.

We can't say for sure this is happening in humans. No one did a human study where they measure cognition with people having intercourse and not having intercourse but you know somewhere to go with the research but it would be probably hard to get funding for that i i i suspect yeah yeah absolutely well you know super fascinating discussion um sundry what i often do with um i interview a whole wide variety of guests on this podcast. Not everyone is a scientific researcher, but I'm always intrigued for those high-level researchers who come in and speak to me. Have you changed anything in your own lifestyle

since you started doing your research? Yeah, good question. So I was already a convinced runner. So, you know, I'm just happy to, you know, have another reason to say, well, you know, at least it's good for my brain. And if I'm not training for a race, you know, I say it's just, you know, a good, healthy, you know, things to keep going. And then definitely the intermittent fasting. So I definitely started to do intermittent fasting, you know, as soon as we got, you know, some of the mouse study out. So I'm indeed not, you know, asking participants to do things I wouldn't do myself.

So intermittent fasting is definitely one of them. The PhD student who is, you you know on the project she's doing intermittent fasting herself for example and some people that were in my lab before were very much into calorie restriction you know after they they saw the data so um and then we try to have a healthy lifestyle as well at home you know my kids know you know what's good and what's bad my kids do as well, actually. So it is like... I hope they don't rebel when they get older and go, I'm sick of all this healthy living that daddy keeps talking to us about.

Yeah, no, no, that's a danger. So we try to apply it at home with exactly a little bit, you know, of flexibility indeed, because you don't want to alienate them. So it's tricky though, isn't it, as a parent? No, it is. Yeah, yeah. Because you want to do the best for them and then once in a while of course yeah. Yeah absolutely. Well no I think it's so telling what researchers do and what research compels them to change

and I think some intermittent fasting is probably a really good tip for people who are listening. Yeah and then I mean it's not that hard to do um and usually i do that i will never do that on the weekend because this is where you know maybe i'm with friends or family and it would be really hard to do intermittent fasting on the weekend some people do though is it not easier at work when you're busy and you're actually almost too busy to eat exactly so at work it's very easy very very easy to do at work yeah i think that's a great tip. Well, Sandhya, look, what I, you know, what I try and do right at the end is to leave people with a bit of positivity. And the whole point of this Feel Better Live More podcast is to inspire people to become

the architects of their own health. And I think the conversation today has shown just what a healthy lifestyle can do for our brain health and, you know know potentially the growth well not potentially the growth of new nerve cells can can you leave the listener with a few top tips i mean it's probably you probably already mentioned them but maybe four top tips for what they might be able to do to improve the health of their brain yeah i mean i think the number one good news in fact some people were not aware is that you can still make new neurons in your adult brain, so nothing is lost. But these new neurons have a functional impact on learning memory and your mood.

And this is why trying to live the best you can to keep the neurogenesis going is important. And then the way people can do that is that trying to know, trying to sleep well and, you know, limit stress. But sometimes it is difficult. So if you cannot limit stress, can you balance it out with maybe a good diet? You know, eat, you know, lots of fruit, vegetable, fish, if you, you know, are not a vegan or, you know, vegetarian. And then finally try to exercise, do something you like. Yeah.

Brilliant tips. Sandrine, thank you. Um, are you on social media? I haven't noticed a huge presence and it may be because you're too busy actually doing real research that we can all apply in our lives. Um, but for people who are listening to this,

who, who might want to connect with you or let you know what they thought of our conversation today, what's, I mean, do you, you know, can you, can you sort of point people as to where they

can find you? So yeah, I mean on Twitter. What's your handle? It is Tudrine, so it's T-H-U-R-I-N-E, at Tudrine. But if you search Sandrine Touré, you will find that on Twitter. And I will put links to this and your TED Talk and some of the other articles you've done. And then we have a lab webpage, but this is linked, I think, to the Twitter account

and to the TED Talk probably. So for each episode, I create a show notes page on my website and I'll make sure there are links to your lab, there are links to your Twitter and some of the articles that you've done as well. Thank you. Thank you for joining me today and good luck with all your research.

Thank you. Thank you. Thank you for joining me today and good luck with all your research. Thank you. Thank you. That concludes today's episode of the Feel Better Live More podcast. I found that conversation super inspiring and I hope you did too. I think it's amazing that the more we learn about the body and the brain,

the more we understand the critical importance of the lifestyle choices that we make on a daily basis. As I wrote in my very first book, The Four Pillar Plan, consciously change your lifestyle and you will unconsciously change your biology. That phrase is very apt in the context of today's episode and brain health. As always, do let Sandrine and I know on social media what you thought of today's episode and what small changes it has inspired you to make in your lifestyle you can see everything that we talked about including links to more of Sandrine's work her articles and her TED talk on the show notes page which for this week is at drchastji.com forward slash Sandrine, which is S-A-N-D-R-I-N-E. As we discussed on today's show, chronic stress can have damaging effects on the brain in the short term, as

well as the long term. My brand new book, The Stress Solution, really dives into this topic so that you can understand where stress lives in the modern world and more importantly what you can do about it. The book is full of simple and accessible strategies that you can apply in your own life to reduce your stress levels so that you can live a happier and calmer life. Since the book came out just over one week ago, the response has been phenomenal. So far in the first week of release, there are an incredible 70 reviews on Amazon. All of them have been five star. Thank you to all of you who have already bought a copy.

You have helped send the book to number one in all books, which means that I can get this information out to so many more people. If you haven't got a copy yet, you can pick one up right now in paperback or in the audio book, which I am narrating. All of the international book links for The Stress Solution are available at drchastity.com forward slash book. If you do enjoy my weekly podcasts,

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