The Art of Aging Well

Hello welcome! I would like to start our program. We still have people signing up, but since we have a livestream audience, I'd like to start relatively on time. I'm Gina Vild, Associate Dean for Communications at Harvard Medical School. And I'm very excited to be here today. This is my 10th year presenting in conjunction with seminars, and this is our 18th Longwood Seminar. And this, of course, is our inaugural seminar. We are very excited. This forum was developed 18 years ago to try to share the knowledge of Harvard Medical School professors with our neighbors and our surrounding community.

Since then it has grown exponentially and we now broadcast it live around the world. So I would like to thank you all for being here tonight and thank you for your participation on our social media channels and for taking the time to attend in person. This is truly a treasure of an event and for Harvard Medical School and you are part of that treasure by being a returning audience. Now I would like to ask: Who is this their first Longwood seminar for? Oh great, excellent. Okay, and how many of you, quickly raising your hand, have been here before?

Good good good. Thank you. There are so many familiar faces here and as they said, it's my tenth year and it's really wonderful to welcome you back here tonight. We were wondering if maybe the snow would keep people away, but I know this topic is of particular interest and the snow didn't deter anyone tonight. I would also like to welcome those of you who are watching the live stream via our Facebook and YouTube channel. Typically, if this event is typical of previous years, we will have viewers from 36 countries and an audience in the tens of thousands, so you are also an important part of our Longwood Seminary community, so thank you for joining us . .

We select topics for Longwood Seminars based on our students' preferences. So we offered 10 themes and four themes were chosen for this year. Tonight's topic, The Art of Aging Well. On March 28 we will offer The Science of Pain Management. April 24, Bridging East and West: New frontiers in medicine. And on May 9, our final seminar will be Weighing the Facts of Obesity. As you can see, we choose our themes based on your feedback. Therefore, we will send you surveys in the coming weeks and encourage you to give us honest feedback: what you liked, what you didn't like, what recommendations you have for the future that will make these seminars even more attractive. meaningful to you?

Tonight's topic is one of our favorites of all the seminars we have offered in previous years, so we are delighted to be able to offer it to you with this particular panel of experts. And since we know that this topic is of interest, I want to share with you some additional resources on the topic. I invite you to take a look at the Harvard Health publishing website, and that web address is www.health.harvard.edu. If you forget, you can type Harvard Health Publishing. There you'll find many additional resources: special health reports, newsletters, e-learning, and blogs about

aging

well

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We also recently launched a program called Live Better, Live Longer. We also offer a lot of resources on that topic. The website is www.health.harvard.edu. And tonight, if you're interested in learning more about Harvard Health Publishing, Cathy Finn, would you raise your hand? She's over here. She works with Harvard Health Publications and is available after the seminar to answer any questions she has, and she also has literature on the table outside near the registry. On the screen, she will now see information about how to earn certificates of completion, as

well

as professional development points for teachers.

And teachers have long been part of our core Longwood Seminars audience and we are delighted to have them here again tonight and this year. We also invite you to view the Longwood Seminars website on our HMS website, and there you will find content on many of the seminars from previous years, the topics of which are mostly EVERGREEN. This is an opportunity to truly expand your experience with Longwood Seminars. Our speakers will answer questions at the end of the presentations, and you can write yours on the card that was given to you when you registered, so save it and our staff members will move through the halls and you can hand them the questions and we will send them to you to the moderators.

Don't worry if you're not in the auditorium tonight. If you are watching us via the live stream, please post your questions in the comments section on Facebook and YouTube with the live stream, or you can tweet them to us at #HMSMiniMed. And we invite you to be part of our conversation on Twitter all night long. So now for tonight's seminar. Something we should all know about the art of

aging

well. Actor George Burns, who lived to be 100, once humorously said, "You can't help getting old, but you don't have to get old." So was he right? Our experts will tell you.

Tonight, the good news is that people are living longer and enjoying a better quality of life than they did a generation ago. We better understand how diet, exercise, a positive attitude and staying socially connected can help us age well. But what does it even mean to grow old? Why do people age differently? And why do some people we know tend to completely defy the aging process? And what are the latest discoveries that can help us stay healthy well into old age? Many Harvard scientists are working to answer those same questions. We are fortunate to have some of our most experienced experts here with us tonight.

They will share their research that can help us live longer, healthier lives. I am delighted to introduce you to our panel of experts. Dr. Alexandra Touroutoglou is an instructor in Neurology at Harvard Medical School and an assistant in Neuroscience at Massachusetts General Hospital. Dr. Lewis Lipsitz is a professor at Harvard Medical School, director of the Hebrew SeniorLife Aging Research Institute, and chief of the Division of Gerontology at Beth Israel Deaconess Medical Center. And I think this is a repeat of the command performance that he spoke at the Longwood Seminars a few years ago. And first, you'll hear from Dr.

David Sinclair. Dr. Sinclair is Professor of Genetics and Co-Director of the Paul F. Glenn Center for the Biological Mechanisms of Aging at Harvard Medical School. He will share some of his exciting new discoveries about aging. Again, thank you very much for being with us for our eighteenth year and please extend a warm welcome to Dr. Sinclair. Thanks, Gina. Thank you all for braving the snow here in Boston, and welcome everyone online to this Longwood Seminar series. We have three big talks about that tonight. Well hopefully at least two, we'll see how mine goes. So I'm here to start the night and give you good news and bad news, okay?

The bad news is that we were all born, almost all of us, in the 20th century. And that means that we may not live to see some of the amazing things that I'm going to tell you about tonight, but the good news is that scientific progress is moving extremely fast and we may actually have been very fortunate to be able to catch just the beginning of the equivalent of human flight, but to grow old. And I was sitting here with Professor Lipsitz talking about how privileged we are to work in this day and age where miracles seem to happen.

So on my first slide, I asked you this question: What will be the biggest global change in the next 30 years? And if you open any magazine or newspaper as we used to call them, your iPad, you will see that there is a lot of excitement in the world of technology, mainly, about how our world will be revolutionized. One day, very soon, we will be able to talk in any room and turn on the lights; In fact, we can already do it, what am I saying? The future is here. But what I want to say tonight is that 30 years from now, these devices will seem like a blip in history compared to what's going to happen to our biology and to the changes in medicine, because I'm very lucky as are the two speakers tonight from I have a front row seat to what is to come and I am very excited to be able to share with you some of that view here tonight.

Most of the public has no idea how close we are to some really amazing drugs that are coming, and I really... I get out of bed every day thinking, I can't wait to see what's next. Well, here's a boy. He looks a little like me. According to this genetic test he did on me, he is related to me. Thank God. Otherwise my wife would have been in a lot of trouble. So Benjamin is a new generation of children in the developed world and increasingly throughout the planet who will be able to live in a world that we can barely imagine, and I hope that after tonight, you can imagine it.

So Benjamin is taking a genetic test by simply spitting into a tube, and he gets a report that tells him where his ancestors came from, what part of the right arm of his chromosome he got from his grandparents and great-grandparents. And in fact, we have genotyped our entire family, so we can use this not only as an educational tool for our children, but to teach them how they will be able to survive in the next century. And I don't say that lightly. Benjamin was born 10 years ago, but there is absolutely no doubt that he will see the 22nd century unless he is very unlucky.

Most children born today will be able to be healthy until they are 90 years old and even up to 100 years old, and that is if we do not make a breakthrough. The kind of breakthrough I'm talking about tonight could allow us to live even more healthily, and that's the main point. This is a snapshot of many of my family members in 2005, okay? So now we go back 13 years. And just to orient you, we have my grandfather on the right, my grandmother in the middle who is 80 years old, my mother who was 62 years old at the time and my father who was 65.

And this is my wife on the bottom right. I show it because of all the people who have numbers over their heads, only one is still alive. The other three had some pretty horrible times during the last years of their lives. Now we are talking about brain aging. Now, brain aging is one of the most traumatic processes that has ever happened to humanity. If anyone here, and I'm sure many of you have had family members who have experienced some dementias, Alzheimer's is just one of them, you will know how horrible it is not only for the individual, but particularly for the families themselves. .

And people can spend a decade in this state. In fact, I tell you that actually half of the population, the adult population of the United States, has at least one chronic illness, and that's what we spend 86% of our health care on. So what if the number of chronic diseases could be greatly reduced? And instead of just keeping an organ or tissue healthy, which is what we do when we go to the doctor and they prescribe a statin for our heart and a pill for our blood pressure, that's great, but what about the rest of the body? ?

And throughout the 20th century and to this day, most researchers and clinical trials here in Boston and around the world focus on treating a disease, but now we have the knowledge and ongoing clinical trials where one drug can potentially treat 20 different diseases. and as a side effect, you will live longer and healthier. So we'll get to who's still alive in a minute. Now I am often asked: Dr. Sinclair, Professor Sinclair, aren't you worried that you are condemning us all to overpopulation and who wants to be old any longer anyway? And what I'm trying to show on this slide here, I hope it's clear, is that if we're successful, at a minimum, what we're going to have is that the last decade of life, or even longer, is going to last.

Be as healthy as when I was between 20 and 30 years old. And I know it's possible. There are many of us who genetically and soon pharmacologically will do this, and we will hear Professor Touroutoglou talk about it. I hope I have convinced you that this is a valid quest. I think I'm preaching to the choir, but people often forget that we're not keeping people older longer, we're talking about keeping people younger longer. So you don't have to worry about getting cancer at 60 or heart disease and having a stroke at 70 or 80. And we can do this very easily in the laboratory.

I have mice in this area...well my lab is upstairs...we can keep them alive for much longer and as far as we know they die pretty quickly and painlessly and this is what the future holds. And when this happens, we will look back and say, wow, I would never go back to those days. In the same way that we remember the first part of the last century, whenpeople died from an infected splinter. So how is this possible, you might ask? What has been the great advance? And the biggest advance has been the realization that our bodies are not just cars that wear out: that's the old view of aging.

And of course, according to this analogy, there is no way that anyone can develop a drug that can fix everything, because all the different things break down. It would be like we threw a wrench into this car on the right and everything worked again; that's impossible. But our bodies are much more complicated than a car. It's the equivalent of finding the shop's repair staff. Our bodies are capable of immense repair. They just lose their memory on how to do that. They become less and less able to repair themselves. If we take my son, for example, he cuts himself, gets an infection and will heal very quickly.

Why does that decrease as we get older? And over time it gets so bad that you can die from an infection when you're old? We believe as a field-- not just my lab, but a whole group of hundreds of labs around the world-- that I finally understand how it is that the body when it is young can fight disease but not when we are older. Not only that, not only the illness, but also how we feel: why do we have more energy when we are young than when we are older? Why do we groan when we get up from a chair or bed as we get older?

We take it for granted. It's almost so common that we don't even ask ourselves why this happens? So the good news is that there are sets of genes that researchers around the world have discovered control the health of our bodies. Now there are some ways to make them more active. We now know that exercising, staying lean, dieting, and eating a good diet are good for you. Even following a Mediterranean diet and consuming these stressed plant molecules is good for you. Why is that? And I don't think it has anything to do (or not much, I should say) with antioxidant activity.

What is happening is that you are activating genes that repair the body and tell the body to be in a better state and to try to survive during these times of adversity when we are running and hungry. Some of those genes are called sirtuin. There are seven of them in your bodies. All the world has them. Without them, you would be in real trouble. But we can engineer mice to have more of these genes, and in many cases the mice are healthy. And in a couple of cases, in a couple of genes, the mice lived longer, and they lived longer because they didn't get the diseases of old age.

Now we can't genetically engineer ourselves, at least not yet. There are certainly some people here at Harvard who are working on some gene therapies to help people have a better genetic repertoire, particularly to repair what is lost over time in terms of genetic diseases. But let's say that during our lives, what is most likely to be beneficial to us are medicines developed through traditional means. And the exciting thing is that now we know how to do it. It no longer surprises anyone in my field that within the next five years someone is going to make a drug that not only treats heart disease, but treats almost every disease we get as we age.

And I'm not the only one doing this anymore. I used to be one of the few people: almost every month there is a new big discovery and/or a new company that started making this a reality. So in my research, what we're looking for is a molecule that activates these sirtuin pathways that I just mentioned, the genes that we think make you fitter when you exercise and when you diet. This is a pretty remarkable molecule. This is called NMN. Don't confuse it with M&Ms. M&Ms aren't so good for you. NMN is what the body uses to make a molecule called NAD.

Now NAD turns out to be a remarkable molecule. It's very small, it's just a chemical substance. It is related to vitamin B3. And what we used to think, when I was in high school, was that NAD was just important for maintaining chemical reactions in the body. All he did was do housework, not that doing housework is a bad job, it's just not particularly exciting. What was discovered about 20 years ago is that NAD also controls the body's defenses against disease by activating the sirtuin enzymes that I told you about. So now what we can do is feed cells and even animals and even people in clinical trials with molecules like NMN and increase their NAD levels, increase their NAD; these are called NAD boosters.

And what we see is actually quite remarkable in animal studies. And very soon we will know if this works in people too. Now you might be wondering, Dave, why are you pushing NAD when we already have a lot of it? Well, first of all, NAD is extremely important. Without it, you're dead in about 30 seconds, so you want NAD. But do we have enough? Well, I think we definitely have enough in our 20s. My son has enough. If they took his blood and measured it, he would have copious amounts of NAD. The problem is that at age 50 you have half the levels you had when you were 20.

And as a result, not only are your chemical reactions slower, but more importantly, your body no longer fights disease. . like I used to do. So when we give this NMN to old mice, what we do is we just put it in the water supply and they drink it for a few weeks, and then we ask, what happens to those old mice? Let me show you what happens to these mice. Now I admit these are black mice on a black treadmill, but I hope you can focus on their tails and ears. Now one of these mice has been drinking NMN for a few weeks and the other has not.

And this is a fairly typical result. We are about to tell the world in a publication that we can significantly increase the resistance of old mice to the levels they had when they were young again. And the way this works is that it actually builds new blood vessels in the muscle (and we think of the brain as well) so that it can remove toxins from the body that build up during exercise and aging. So this is great. What this means is that if this could be done for humans, for us, we could take a pill every morning and get the benefits of exercise without necessarily having to exercise.

OK? It sounds too good to be true. And I agree, it sounds too good to be true, except so far it is true. This is cutting-edge science, it is in the best scientific journals in the world, so let's hope it translates to people. You might be wondering: is this an excuse to just sit down, take a pill, and eat chips? The answer is no, it's not an excuse, because if you're fit and you take this molecule, if you run while you drink this molecule or you drink it and then you go out for a run, these mice can now run more. more than double that of them.

Here we are developing super mice. Now that we just had the Olympics, I'm not sure what will happen in the next Olympics if this turns out to be true, but what it means is that we can finally achieve the best that our bodies can give. not only when we are young, but even in old age, so that we do not groan when we get out of bed in the morning. And in fact, if we start to lose our mobility and are stuck in a wheelchair or bedridden, it's those people who would absolutely need exercise in pill form... for those people.

And imagine if they could start walking or exercising again and reap the benefits of that, that would be a beautiful positive cycle that would not only allow them to exercise, but also keep the rest of their body and brain active. - more blood flow too, which I'm sure we'll hear later about the importance of this. So this molecule and others have also been working on it for years. Over the past five years, we have seen that NMN and a related molecule called NR, when given to old animals, protect them against a wide variety of diseases: diabetes, memory loss, hearing loss, vision loss, inflammation . , even improves wound healing.

This is, as far as I know, the closest thing to an aging reversal. So we'll see how far we can go and if this really applies to people. The good news is that, so far, it is a very safe molecule or group of molecules. I mentioned it's basically a super vitamin. The other good news is that it is a natural molecule, we all have NMN in the body and NAD, but we lose it over time and all we are talking about is replenishing those levels. There is a clinical trial underway here at Harvard Medical School and Brigham and Women's Hospital, and it is a very exciting time for my colleagues and I to see if we can translate the last 20 years or so of amazing discoveries in animals to finally via To the People.

Now I have no illusions that this is going to be easy or quick. Most clinical trials cost hundreds of millions of dollars and also cost, in terms of time, at least five years. But how long has humanity been waiting for something like this? And how big is the reward? It's in the trillions of dollars of the economy. This is money that can be used for other things, such as education and the environment. And we won't have a higher GDP, we'll actually have... or loss of money in the economy, we'll actually have a lot more money to spend if we're able to keep people healthier for longer towards the end of their lives. life.

And I'm not an economist, but all the economists who study this say that this is the best investment in terms of the health care system, and if we don't do something, we'll be in trouble anyway. Let me finish by highlighting the member of our family who has survived. My father is now 78 years old. He is in Sydney, Australia, where he landed after escaping Hungary in 1956 with my grandmother. Of all the people I've mentioned here in my family who had numbers over their heads, my father was very interested in our research and started taking some of the natural molecules we were discovering about a decade ago.

Now, for those of you who say, Dr. Sinclair, that a scientific experiment needs more than one person, I am absolutely aware of that. I'm not going to post this result anytime soon. But it is interesting. He certainly he's not dead yet. In fact, he's gone from a person who wasn't looking forward to the next 10 years of his life: he had retired, he was slowing down, he didn't expect to live much longer than another 10 or 15 years. So what happened to him? This is what he did last year. That should say 2017. So, top left he's climbing trees in Germany and putting on skis on the zip line.

Above right is climbing the highest mountain in Tasmania in Australia. The lady on the left in the red shirt is my ex-girlfriend. Go figure. I have nothing... I have no problem with that. It's my wife who feels it's strange. She's climbing in Montana. She was rappelling or rappelling down a mountain. She has gone caving, bike riding, whitewater rafting. And almost everywhere she goes, people say we've never had someone her age do this before. Again, it's just an anecdote, but what I would like to make clear, at least, is that this is what the future will be like.

This is what we are aiming for. People aged 70, 80 and over will be able to have a life that is not just pain and sadness for them and their families. And you know what? My father started a new career. He was so optimistic about the future that he started working for a non-profit organization at the University of Sydney and now oversees clinical trials. But at his age, when I first showed it to you, if he had said, you're going to start a new career when you're 77, he would have said, tell me another one. So he's got a new lease on life, I'm looking forward to seeing how he does over the next decade, and so is he, by the way.

Finally, I just want to finish by giving you a little idea of ​​the extent to which this can happen. I did an experiment again. I like to experiment. And sometimes we experiment on ourselves. Now I hope you can see that: This is a line from a local company called Inside Tracker and, in full disclosure, I recommend that company. But they are the only group I know that has a true scientifically based algorithm to estimate what your biological age is. And then I said, sure, test my blood. They've tested thousands of people now. So they took blood samples, and I hope you can see that, although he was only... at the time he was about 46 years old, according to their algorithms he was about 10 years older.

And they measure five things: glucose, testosterone, and some other things that basically correlate with longevity. And I didn't look very healthy and I thought, this would be really bad if I died young. So I decided to do something about it. And what I did was... the first thingWhat I did was be more conscious of what I ate. And I lost some weight, I lost about seven pounds, which didn't hurt, okay? Full disclosure: that's one of the best things you can do if you're a little overweight. But also what I did was test some of this NMN molecule.

We had some that were safe on mice and I was prepared to try them. And what you may see in the next few months is that this company came back... they didn't even know what to expect, they just came back and said, "Your blood test now predicts that you are 31.4 years old." age. Then I jumped for joy. This is fantastic. Now I've put on a little bit of weight since then, but the thing is, if this is true, then it's pretty easy to give yourself a little more life, and that's what we're talking about today. And I'm very excited to hear from the next two speakers who will tell us even more interesting things about their work on the species we call human beings.

So thank you very much. I'm aware of. So now, without further ado, I want to invite Alex. Alex Touroutoglou is a world-renowned human aging expert and I can't wait to hear what he says. Thank you. Thank you so much. So it's a pleasure to be here. I'm going to introduce you to SuperAgers and I think David's dad is probably a SuperAger. Let's take a look at the SuperAgers. Let's see what SuperAgers are. We all know that memory and cognition often decline with aging. For example, with young adults, you score around 13 on a memory test. Typical older adults tend to perform much worse.

But there are some people in their 60s and 70s who continue to perform as well or even better than young adults 40 years younger than them. This unique group has resisted the cognitive decline typical of aging. We call this group SuperAgers. We will start by describing what a SuperAger is. And today I would also like to show you how your brains are different. As neuroscientists, we had to gather the SuperAgers to enter the scanner and look inside their brains to discover their secrets. There are several ways you can look into the brain using MRI. You can look at brain structure, you can look at brain networks, brain activity, and you can look at what parts of the brain are activated when people perform a task.

Therefore, today I am going to present three studies to understand brain overaging. Study one will look at brain structure, study two will look at brain connectivity in SuperAgers, and study three will look at what parts of their brains activate when they perform a memory task. Let's start by describing the definition of SuperAgers. One of the reasons I think our studies are interesting is because we focus on people close to or just after their retirement date, mostly in their 60s and 70s. And we're interested in seeing who performs: which older adult performs as well as young adults in their 20s.

Based on the laboratory tests, we give them a memory test, a memory test that includes 16 unrelated words. The challenge is for older adults who will have to memorize this list and then remember it, to repeat it after 20 minutes. Most older adults will remember after a delay between eight and ten of those words. Young adults will remember 13 or more words. SuperAgers will also remember 13 or more words, and in some cases, they will remember up to 16. So, it's really remarkable for SuperAgers, that this group that is in their 70s has a memory, a sharp memory, the same. I remember him as someone four or five decades younger.

So based on our lab testing, we define SuperAgers as those older adults who perform equally or even better than younger adults 40 years their junior. We first analyzed their gender and education and found no differences. There were no differences in either gender or education between SuperAgers and typical older adults. In our study, it turns out that we had 17 SuperAgers and 23 typical older adults who did not meet the criteria for superior memory. So, next we ask ourselves: what makes a SuperAger a SuperAger? So we looked at the structure of the brain in the first study. We use MRI.

Mass General Hospital is the first US hospital to establish a diagnostic and research program specific to MRI. MRI uses strong magnetic fields to create images of biological tissue, in our case, the brain. I present here a schematic organization of the scanner and the control systems that we are using. In addition to the scanner, we use a series of amplifiers and transmitters that are responsible for recording the data and sending the magnetic resonance signal to the powerful computers where we analyze our data in our laboratory. In the first study we measured the thickness and size, the volume of gray matter.

Gray matter is the part of the brain where all thoughts and sensations actually occur. There are several ways to display MRI data on structural MRI scans. One way is to use a volume template. Another is a folded brain or an inflated brain. I will use both volume and inflated brain to present... to show you the data. Okay, so let's look at the data. Let's see what study one showed about SuperAgers. We observe its bark. The cortex is the outer layer of brain cells that is really important for our critical thinking ability. We knew from previous studies that the cortex, as well as other parts of the brain, normally shrink with aging.

We compared the brain scans of SuperAgers, typical older adults, and younger adults. And what we found is that, as you see here, the red spots, we found that all of these regions were thicker in the SuperAgers than in typical older adults. These are the areas where there was more gray matter in the SuperAgers. And it is not just a few regions, but it is distributed throughout the crust. I group them according to their function and as you can see, the ones included in the blue outline are regions important for attention and the ones included in the yellow outline are regions important for memory.

Surprisingly, some of these regions were truly young. And when I say young people, I mean that they were statistically indistinguishable from young adults, as we'll see on the next slide. You can see here that the bar graph shows the cortical thickness in these two example regions, the medial prefrontal cortex and the middle cingulate cortex. Thickness in SuperAgers was the same as in young adults. It was thicker in this region than that of typical older adults, but was about the same in the young adult. Same thing here in the medial prefrontal cortex, this region showed full preservation.

It was noticeably thicker in the SuperAgers than in the typical older adult, but was statistically indistinguishable: comparable in size to that of young adults. As Hippocrates once said, "It is much more important to know which person has the disease than which disease he has." So we looked inside each individual brain to better understand the brains of SuperAgers. And here we are. By looking inside the brain, we realized that if we measure the size of brain regions, we can predict how the individual will perform on the memory task. We measure brain size before the task and can predict how that individual will perform on the task.

You can see here that this individual, who had the largest hippocampal volume, performed among the best in living memory. And this individual, who has the smallest hippocampal volume, performs among the worst in living memory. The hippocampus is a deep region of the brain that is really important for memory. So, the larger the hippocampus, the better the memory. Summarizing the data from the first study, we saw that although memory decline may be the rule, there are exceptions. SuperAgers show youthful brain structure in regions important for attention and memory. The thicker the brain regions, the better your memory performance.

But to understand the brain it is not enough to focus on its structure. Brain structure is not the whole story. You should also understand its wiring. Brain activity is important to understanding the brain because no region of the brain is an island. Brain regions are connected to each other, they communicate with each other and are part of a network. And when regions are part of a network, they typically communicate with each other and work together. A growing number of studies have looked at the aging brain from the perspective of brain networks and connectivity, and there are several theories that have suggested that cognitive decline in aging may be the result of disruptions in brain connectivity.

So we looked at brain connectivity and wanted to compare SuperAgers to typical older adults and, again, to young adults. And here is the data. As you can see here in red and yellow, these are the regions where SuperAgers were more strongly connected than typical older adults. There was no region in typical older adults that had greater or stronger brain connectivity than SuperAgers. So the SuperAgers were more connected. Their brains were more networked. Again, as we saw in the anatomical data, you can see here that the strength of connectivity in the SuperAgers was noticeably stronger than that of typical older adults, but was actually comparable in magnitude to that of young adults.

We also look for another clue in the individual brain. Here, we measure connectivity in the deep region of the brain, the hippocampus, and in the cortex, the posterior cingulate cortex. And we found that SuperAgers had stronger connectivity in these areas, and the stronger the connectivity, the preserved connectivity also predicted their memory performance. Stronger hippocampal connectivity, better memory performance in older adults. Taken together, the data from study one and study two, we have established that SuperAgers display youthful structure and youthful brain activity. Not only have their neuroanatomy been preserved, but their brain networks have also been preserved.

But if you think of SuperAgers as an extreme group of typical older adults, it's not enough to simply show preserved anatomy and preserved connectivity, you need to look at how these groups are prone to memory problems differently, if there is a difference. You need to see what the difference is between them when they actually perform the task. And that's what study three tried to do. So in study three, we measured brain activity in response to a task. We look at which parts of their brain light up and activate when they perform the memory task. So we put them in the scanner, gave them a memory task, and looked at their brains. fMRI is the first fMRI technique discovered by Jack Belliveau in 1990 at Mass General Hospital and at the research facilities where we currently perform our imaging studies.

In 1991, the prestigious magazine Science published his article and also included the image of the first scan on its cover. After that, fMRI became widely available and now allows scientists to study the brain in a non-invasive way. The basic idea is to look at the brain and try to identify critical points of brain activation in response to tasks. And here is the data. The brain maps here show the hotspot: activation hotspot regions in SuperAgers versus typical older adults. Before we talk about what we see here, the critical trigger points, let me focus for a moment on what we don't see.

And in particular, these are the regions that are traditionally involved in memory. SuperAgers and typical older adults performed the memory task the same way in terms of memory regions. They also activated their traditional memory regions to the same degree. The difference lay in another region. The difference lay in the middle cingulate cortex, a region involved in many functions, but most importantly, motivation. When this region is stimulated, the will to persevere is awakened. This means that SuperAgers approach the problem differently than typical older adults. They were more motivated, they didn't give up. And not surprisingly, when we extracted the signal from this area, we found that those individuals who activated the middle cingulate cortex more performed better in memory performance.

So, taking the data from all three studies together, we found no differences in memory regions when SuperAgers and typical older adults performed a memory task. But we did find a difference in one region that is really important for motivation, in what I call tenacity. This region is important to move forward when you face difficulties and face a challenge. Summarizing the three studies together, all of our superaging work, I wanted to show you today what makes aSuperAgers be a SuperAger. Well, for starters, a young brain in an older body. We are trying to piece together the puzzle of the super-aged brain.

It is a puzzle that is far from complete. We have seen that SuperAgers have avoided this cognitive and memory deterioration. They show a keen memory despite their age. They have a youthful structure, useful brain connectivity, and when faced with a difficult task, they become tenacious. We believe that understanding SuperAgers is the first step to understanding successful aging. If we can understand what makes them SuperAgers and what keeps them young with memory capabilities, then we will be one step ahead in understanding what healthy aging could mean for all of us. I would like to end by asking an important question: can you turn a person into a SuperAger or are you born with it?

And with that, I would like to thank you and introduce you to Dr. Lipsitz so you can hear all the interesting facts about healthy aging. Thanks Alex. Well, thanks Alex. I'm going to take a second to look at my slides here. Well great, good night everyone. I am a geriatrician, which means I am a doctor who cares for older patients, as well as a clinical researcher. So what I would like to do is speak from the perspective of a geriatric doctor (that doesn't mean I'm old, it just means I study old people) and share with you some of the new advances in clinical research and aging.

Interestingly, aging is a young field. A century ago, very few people lived to old age. In fact, the average life expectancy in 1900 more than 100 years ago was only 47 years. And as you've probably heard in the media, now 10,000 members of the baby boom generation, including myself, turn 65 every day. In fact, that was old news: now there are 10,000 people turning 70 every day. This means that people over the age of 65 will soon make up 20% of our population and as a result, as you may have heard, we will face enormous social, medical, economic and ethical challenges. But there is a lot of optimism, because there are a number of opportunities, which I will share with you, to apply advances in science and engineering to improve the health and well-being of older adults.

This simply illustrates the fact that the world is aging rapidly. A variety of different societies can be seen here, with Japan leading the list for having the fastest growing older population. But this is also happening in the United States, and estimates are that by 2030, the number of people over 65 will double from the current 35 million to 72 million. And those over 85 are one of the fastest growing segments of the population, and that number will double from about four million to nine million by 2030. So this is a big change in our society. We currently have around 13% of the population over 65, but they account for around a third of all hospital stays, and almost 50% of the days in hospital a patient can spend, and 50% of the hours in hospital. a doctor spends per patient, which cost Medicare $26 billion.

As you can see, getting older is us and getting older is expensive. This is illustrated here with this story that says: Sorry, we're bombarded with aging boomers, so come back in about 20 years for your healthcare system. Unfortunately, our healthcare system has been slow to adapt to this baby boom population. But the good news is that life expectancy is increasing. The yellow line here illustrates the life expectancy or survival pattern of people in 1900. And as you can see, there was a big drop before age 10 due to early childhood diseases, which we've now conquered, pretty much. . And as time goes by, more and more people are living to an older age.

We generally talk about life expectancy as the number of years a baby born today can expect to live. And you can see here in these successive curves that life expectancy increases over the years between 1900 and 2000. But another concept is life expectancy, and life expectancy is considered the maximum number of years that a species determined can live. And it used to be thought that our life expectancy was really limited to about 100 years of age. But, as you've heard from Dr. Sinclair, there have been some very interesting advances that suggest that perhaps we can increase life expectancy and life expectancy.

In fact, it seems that the older you are, the longer you live. These are actuarial tables that some of our actuaries used to decide how much insurance we should pay, but you can see here that today, a person about five years old can expect to live to about 82 years if they are male or 86 if they are male. You are a woman. Curiously, women have always lived longer than men. They are the stronger sex, I must admit, this is true until very late in life. So the older you are, the longer you can expect to live. So today an 85-year-old person could expect to live to 93 if they are a man and the same age if they are a woman.

So the key to this is to live to 85 and you will have a good chance of living even longer. But that is not enough. We don't just want to live to an old age, we want to live to that age without disability. And I think Dr. Sinclair demonstrated it quite well in his slide, but the goal of us in geriatric medicine and researchers in the field is to decrease the duration of disability. So this top line really shows the current situation. At about age 55, people begin to accumulate illnesses that eventually result in more and more morbidity or disability, and ultimately, perhaps at age 76 or so, they may experience death.

One goal is to extend life to maybe 80, 90, 100 years of age, but if we did nothing about disability, all we would do is extend the number of years, increase the number of years in which we had to suffer. illnesses and disabilities and, of course, that is not good. So what we need to do is shift to the right the time when we might develop a disability and also increase our life expectancy. Ultimately what we hope to do is reduce morbidity; in other words, delaying any kind of illness, any kind of morbidity or disability until the day we die, and then suddenly leaving a healthy life all the time.

And that's what Dr. Sinclair and other scientists are starting to show us we could do with some of the new innovations in aging research. Well, this lists some of the challenges we all experience in the aging cycle. As you know, after a year the challenge is walking. After two years it stays dry, you know? At 16, he drives; At 20 years old, the challenge is to have sexual relations; 30 years old, have children; 40 years old, working; 65 years old, retired. And then the cycle begins to repeat itself. At 70 years old, having grandchildren; 80 years old, having sexual relations; 85 years driving; 90 years old, stay dry; and 95 years old, walking.

This is the cycle I think we are all familiar with. But as we get older, there are two issues that concern us all, and I certainly think it's true that most of us are concerned about loss of memory and mobility; These are very, very important problems that we in clinical research must address while we wait for Dr. Sinclair and his colleagues to find a way to cure all diseases so that we can live a long life. So let's look at these. Memory loss, of course, is a very common problem. Currently, about five million Americans suffer from Alzheimer's disease, and about one-third of older adults eventually die from Alzheimer's disease or other dementias.

This is the sixth leading cause of death in the United States, and for the first time, our government is investing a lot of money in studies to try to address this problem. But the problem is not just for the person who suffers from this disease, it is also a problem for the 15 million caregivers who provide more than 18 billion hours of unpaid care to help manage their family and friends who suffer from Alzheimer's. other dementias. In 2017, Alzheimer's disease cost the nation $259 billion, and that number is expected to rise to $1.1 trillion by 2050—a huge problem. So what causes Alzheimer's disease?

Well, we don't know yet, but we do know that if we look at the brains of people who have died from Alzheimer's disease, there are two proteins that build up in the brain and cause damage. One of them here on the left is amyloid plaque, shown here as this yellow nonsense. And in the... technical term, of course. And here are neurofibrillary tangles, which are dead neurons that contain a protein called tau. So one of the challenges is that if these are really the cause of Alzheimer's disease, we need to get rid of these toxic proteins. A lot of the work being done in laboratories around the world is trying to think of new drugs that can actually absorb them or prevent them from being deposited so that we don't develop Alzheimer's disease.

But one of the challenges is that we can't look at people's brains to try to see if we've been successful or if they have Alzheimer's disease, because that would require a brain biopsy, which we don't do. we are going to do it in living people. So we've been very fortunate over the last decade to have scans, like the MRIs that you've heard about, but special scans where we can visualize these toxic proteins. And one of them is here on the left, it was a PET scan for Alzheimer's disease that injected a Pittsburgh agent, that's what it was called, because it was invented in Pittsburgh, that can actually light up the amyloid in the brain shown here in these yellows and oranges.

MRI scans. In people with Alzheimer's, you can see a lot of this amyloid, but in normal controls, you don't see it. Now, with this exploration, we can see if new drugs can remove these amyloid deposits, and much of the research being done today attempts to remove these amyloid deposits earlier in life, before people develop the disease. . And on the right is just another scan that looks at the brain's ability to use sugar or glucose, and you can see, a normal person on the right has a lot of activity, a lot of red and yellow, whereas the Alzheimer's patient loses that. ability.

We have been working on many therapies for Alzheimer's disease and I wish I could tell you that we have a cure, but we don't. In the meantime, however, we must be able to treat the disease. Therefore, there are many therapies that could slow the progression of the disease and they are listed here. Some of them increase a transmitter in the brain called acetylcholine, and you've probably heard of drugs called Aricept, Exelon, Reminyl that can do that. And they could slow the progression; They are not dramatic, but they have some effect. And the same goes for a drug called memantine that can prevent some of the brain damage.

But one thing everyone can do is reduce their cardiovascular risk factors. Because we know that the same factors that cause heart attacks and strokes are also linked to Alzheimer's disease and other dementias, particularly vascular dementia. Therefore, we must treat hypertension, treat high cholesterol, and treat or prevent diabetes at an earlier stage in life to prevent these diseases. Dr. Sinclair mentioned oxidative stress. We used to think that if you reduced oxidative stress in the brain, that could reduce this disease, but it hasn't had much success. We also aim to prevent the inflammation caused by these toxic proteins.

And also, as I mentioned, we are trying to develop drugs to reduce the deposition of amyloid or tau in the brain, and there are many drugs in testing and many scientists are looking for vaccines to absorb these abnormal proteins. But another thing we can all do is engage in physical and mental exercises. Do those brain tests the SuperAgers are doing. In fact, that could allow you to become a SuperAger. We know that the aphorism "use it or lose it" is true. People who have been active throughout their lives and do cognitive activities tend to have a lower risk of Alzheimer's and other dementias, so it's very, very important to be active.

And one study that I always like to refer to is one that actually took a group of seniors in a community and invited them to volunteer to teach children in elementary school classrooms in Baltimore; this was called Experience Corps. These people who came into the classroom and taught these young children had brain scans similar to the ones you just heard to look at brain activation before and after this activity. And they were compared to a group of people like them who did not participate in theteaching these children. And you can see that in the blue areas there are parts of the brain, using this fMRI, that were activated more in the volunteers than in the controls.

And you can see on the right in the blue lines that activation during a series of cognitive tests actually increased in these people who simply volunteered to work with children in the classroom compared to the red ones, who were the controls. So remember, use it or lose it. What you are doing today, sitting here and thinking, will really help you have a couple more years, hopefully, without Alzheimer's disease. So the second concern we all have, of course, is mobility problems, and they are quite common. About 30% of community-dwelling seniors fall each year, 50% of nursing home residents fall, and this is associated with many injuries and costs of up to $31 billion.

This is not a ham bone, but a human femur. This is the cross section of a thigh from a young, healthy person. And you can see the bone up here with the marrow in the middle. And do you know what this yellow is? It's muscle and the fat is red. Keep that image in your head, because this is the same cross section of a thigh in an 80-year-old person. And what happened? They have lost muscle and developed fat. We used to think this was inevitable, that we all develop this as we get older. We used to think, as shown here, that muscle mass decreases with age in all of us.

But in fact, activity level also decreases with age, we all sit in rooms like this all day, and it is the activity level, the sedentary lifestyle, that is actually responsible for much of muscle loss, not all, but much of it occurs in old age. And the good news is that resistance training can improve muscle strength and size at any age. We took a group of 100 frail nursing home residents who were up to 98 years old and put them through 10 weeks of progressive quadriceps resistance training, simply by lifting weights with their legs. And we found a 113% increase in muscle strength, a 12% increase in walking speed, a 28% increase in their ability to climb stairs, but only a 3% increase in muscle area, so we got a great investment. .

For that small amount of increase in muscle size, we got a huge increase in strength. So it's never too late. We should keep exercising or take that pill David talks about. I won't go there. So, a common cause of falls that interests us all is multitasking. You know, all of you, probably some of you are probably doing it, taking pictures, walking, looking at your cell phone, driving while texting, we multitask all the time. This man crosses the street while he reads the newspaper, not a good idea. In fact, we can test multitasking in the lab by having someone stand on a balanced platform and measuring their actual balance shown here, and this is what happens, these are all the movements you make when you are standing, presumably still, on a balance platform.

We then ask that person to do what is called a dual task. You can stand here and count backwards from 500 by threes, and when you're standing and counting, watch what happens to your balance. Now they swing everywhere. And what we can do with that is draw a circle around it and look at the degree of influence. We can then compare those two circles and calculate what is called dual task cost. This is the cost of doing two things at once: texting while driving. And we can use that cost as a measure to look at how bad your balance is when you do too many things at once, when your brain has to control too many things simultaneously.

So we can improve dual-tasking costs with a number of different interventions, but one that we're using is electricity and magnets to stimulate the brain. This is one of our themes. You have all heard about brain stimulation. This is deep brain stimulation that's used for Parkinson's disease, but we're actually using transcranial magnetic stimulation to try to improve brain activity, or what's called transcranial direct current stimulation, just a small C-cell battery. , you know, attached. in the head can stimulate certain areas of the brain. When we do that, we can look at a given individual (in this case, it's just a 72-year-old woman) and we can look at the cost of standing in the dual task or her increase in influence during the balance test. .

Then we can give them some electrical brain stimulation and measure the reduction in that cost. So this is a very interesting non-invasive intervention that people can do at home that will hopefully eventually lead to a reduction in falls and many older people. And I also hope to do this when I'm slumped at my desk around 1:00 in the afternoon feeling tired, just put some C cells on my forehead. We did 10 daily sessions of this transcranial current stimulation and showed that it could actually improve dual-task balancing costs. Well, one last intervention that I would like to share with you is about vibrating insoles to improve gait and balance.

We developed a little insole that you can put in the shoe and it vibrates a little bit—you can't even feel that vibration—and it showed that it could improve gait and balance in older people. And this is based on a physical principle called stochastic residents which says that a little noise can improve your ability to sense things. Here you can see what the ground is doing on the bottom of your foot. You can see that here. This is simply the feeling of the foot when it is resting on the ground. But when we layer a little noise, that feeling is enhanced.

And by doing so, we can improve gait and balance. Here is a photo of the insole, it can fit inside your shoe and a small battery can fit right into the laces here. And we can actually evaluate his gait on a small walking platform shown here. So, as we walk someone on a little mat while they have 7 left, you can see what their walking pattern looks like, and it's a little irregular, they stumble a little, they take short steps, long steps. Later when we do it again with the insoles on you may start to see a more regular pattern and here we now have an improvement in the gait pattern and hopefully it will develop in such a way that we can prevent falls.

So the good news is that there are many positive interventions that could improve our experience of aging. We hope to reduce disease and disability in old age and hopefully find a vaccine for Alzheimer's disease. I think we will all see an increase in the retirement age and will work until an advanced age of 70 or 75. We are developing age-friendly cities and housing options within cities that have in-home health care and services so we can age. are in place and we don't need to go to nursing homes, hopefully not go to hospitals, and use personalized medicine to really emphasize our own personal goals of care so that we can live a healthy and happy life.

You are never too old for anything. Here's a woman who goes skydiving to celebrate her 92nd birthday. This, I'm sure, will be David's father in a few years. So thank you all for your attention and interest. Do we have time for this? Yes. Okay, we have about 15 minutes of questions, thank you for sending them, to those in the audience. And we also have some questions from around the world, our online audience. So we'll see how far we get, we'll try to keep our answers brief given the time. I have a question at the top and it could be for any of you.

Tell me who wants to do it. The question comes from Bangalore, India. Wow. Would this research help people who are already suffering from the onset of neurodegenerative diseases such as Alzheimer's? Or would they just be healthy people? Well, I will quickly say that a lot of the research with people who already have Alzheimer's disease in later stages has not been as successful, which is why many of the new studies look at the disease in earlier stages. But it's very hopeful that maybe we can develop some ways to get rid of these toxic proteins and other causes of disease even in old age.

And in the meantime, much of our research is trying to improve the quality of life for people already suffering from Alzheimer's and other neurodegenerative diseases. So I think that while research is being done, we need to really focus on quality of life, even if people have Alzheimer's disease. Well, this one is for Alex. What are the age ranges and categories of SuperAgers and what impact does exercise and blood flow have? Good question. Well, the SuperAgers in our study were close to their retirement age. The SuperAgers in our study were near their retirement age. Between 62 and 80 years old.

They came from all walks of life. There was no difference in education, there was no difference in gender as we said. Can we hear me now? I may have to hold it. OK. Maybe... That's good. I'm sorry. I was saying that they can… SuperAgers come from different walks of life. There were no differences between SuperAgers and typical older adults in their education or gender. Exercise has been shown to improve cognitive function in older adults, and although we don't yet know if SuperAgers exercise more, we can predict that SuperAgers are more active in their lives. Future studies will need to systematically examine and longitudinally follow older adults, those who have become SuperAgers and those who have not, to look at their exercise pattern.

Alright. This is a question for me, I think. How long will it be before the NMN molecule is available to the public? Are there disadvantages? Well, we're in phase one of clinical trials across the street, and what that means is we're just looking at safety. And then there are phases two and three, which at best take a few years to overcome. In the worst case, something will come up and stop us. Therefore, it will not be available as a medicine anytime soon. A few years, maybe? If we are successful and lucky. That said, there are related molecules that are available and sold.

And I can't vouch for them because they haven't been fully tested in humans, but there have been some clinical trials with supplements and so far they seem to raise NAD levels, which is what we see in mice. But are there disadvantages? Basically, is there any risk? Of course, there is always a risk when you introduce a molecule into your diet. I mean, don't quote me, I certainly don't recommend you do this, but I can assure you that we haven't seen any serious drawbacks or anything to worry about in the mouse studies. There's a study at Washington University in St.

Louis, and they fed a molecule called NR, which is a relative of our molecule NMN... no, actually they also gave them NMN for a year, and the mice... the side effect was that I had slower aging and there were no physical drawbacks. But of course, a mouse is not a human, and that's why we're taking the time to do these clinical trials to make sure they're safe, because if we're going to take these molecules, you're probably going to have to take them for many, many years to obtain lasting benefits. Alright, I'm asking questions, okay. Are there genetic signatures for SuperAgers?

That's a very interesting question. Maybe we can collaborate, David, to see what happens. There are no studies that have linked genes to SuperAgers. This is truly innovative research, there is much more to learn. I could simply make a comment that SuperAgers are sometimes confused with centenarians, who are SuperAgers by virtue of having reached 100 years old. And now there are many genetic studies that look at a variety of genes, and there is not just one gene. But there are some interesting possibilities for genes related to cholesterol metabolism, and it depends on your culture and your background. But it's not just genes, but also environment, lifestyle and behavior that influence whether you will live to be 100 years old.

Yes absolutely. Which brings us to our next question, which comes from Facebook, no country mentioned here: what is the correlation, if any, between weight gain and longevity? That one is simple, I'll stick with that one. Avoid weight gain. In studies in humans and mice, it is very clear that being overweight accelerates aging; Not only physically, but even at the molecular level, we see that these changes are accelerating. Obesity will lead to increased inflammation and many chronic diseases. Alright, I think that's pretty clear. Is mitochondrial damage associated with aging? Yes, the answer is yes, but not yetWe are sure if it is an aging factor or not.

It's probably because if you damage the mitochondria in mice or, unfortunately, there are genetic diseases, mitochondrial damage, there are aspects of aging that are seen in those individuals. It's probably part of aging, but it's not the whole answer. And we don't really fully understand why we lose our mitochondrial function as we age, but we're working to reverse that in my lifetime. Ah, so this is for one of you two. Is brain activity related to brain plasticity? That's also another big question. There are studies that have shown that when you perform a task and they measure brain connectivity immediately after performing it, brain connectivity changes.

The strength of the connections between the regions involved in the task increases, suggesting that yes, brain connectivity can be changed through neuroplasticity, through experience. Alright. A question from the public: why is it so difficult to prevent brain aging? We don't know if it is difficult to prevent aging in the brain. There are certainly changes, we have seen it in the normal ones. It has only recently been studied to see how plastic or how much plasticity, but we know that the brain can change; That's what the word plasticity is about. That is why when we use our brain, we can see improvements in many of the functions we perform.

So I think... I'm pretty optimistic about the fact that we can affect the brain, that we can change the connections, we can improve it. But Alzheimer's, when that happens, is a disease. So I think that in normal aging, yes, there are many things that can be done to keep our brain healthy, but when that is superimposed on an illness, that is when degeneration begins to occur. And to date we have not found a cure, but a lot of work is being done to try to achieve it and a lot of money is being invested in research in this field.

Also, to add to that, I agree with Dr. Lipsitz that this is a new area and we don't know if reversing brain aging is difficult or not. Very few people have tried this. What I can tell you is that reversing aging in other tissues is extremely easy, and it is quite amazing how aging can be reversed in just a week. One of the things we're learning now is that it's relatively easy to improve blood flow in the brain, and that could be a big part of early-stage dementia; Vascular dementia is a huge problem. And you know, every time we make a breakthrough in science, we end up realizing that it wasn't as hard as we thought, that all we needed to know is the answer, and that's really why...

We have a place like Harvard Medical School. And I can also tell you that the SuperAgers at least seem to have avoided the fate of aging. They are not affected by the typical aging patterns that other older adults have been affected by. So it's a living example. Yes. Alright, this might be a little controversial. Does taking human growth hormone help reverse aging? No controversy at all. No. There have been studies in the past on human growth hormone. A lot of work was done after surgery, for example, to see if it helped people overcome the stress of surgery, and that showed that it had more toxic effects than beneficial ones.

Although we lose growth hormone, replenishing it has not been shown to reverse aging. Well those are all the questions I have. I think... Take a little more. Do we have more? Barbara? Excellent. It's okay, it's okay. An audience member wanted to know: Is there a link between Lyme disease and Alzheimer's? We know? I don't know... now Lyme disease causes neuronal diseases. It can cause peripheral nerve problems, it could cause brain problems, but those problems are not Alzheimer's disease. As far as I know, there has been no link between Lyme disease and Alzheimer's disease. Okay, I'm going to read this literally, don't blame me.

Alright. And Barbara, you gave it to me. Alright, who wants to address this? Some loss of sexual function in men as we age is not just age, but boredom. New stimuli, etc., etc., can help reverse the loss of function, yes or no? If I dont know. OK. That's really true. OK. Some things slow down a little, but sexual function is still maintained in old age, although sometimes a little more stimulation is needed. Let me leave it at that. We have a question: what influences the pathophysiological changes in the human body to trigger the loss of NAD?

Good question. Why does NAD decrease with age? We don't know for sure. Now what we do know is that there are enzymes in the body that destroy NAD, which seems silly, but often in biology, when you want to alter the levels of a certain molecule, you have some enzymes that produce it and others that destroy it. and that gives you loyalty. Also, what I didn't mention that's interesting about NAD is that it goes up and down with the time of day, and the likely reason you're jetlagged is because your NAD cycles are out of whack. So the answer is: we don't know, but these enzymes that destroy NAD are probably to blame, and maybe we can also develop drugs that inhibit that degradation and keep the levels higher.

That was a good question. This is for Lou again. At what age group do we see a greater accumulation of amyloid plaques and tangles? Yes, there is no specific age, but there are a couple of points. One is that Alzheimer's disease can occur at a younger age, sometimes even in our 50s and 60s. This is an early onset disease, it is perhaps a different disease, which has some genetic predisposition. But we generally see in our practice and in our field a late onset of the disease, and that can occur at any time from age 60 throughout the rest of life.

So the highest prevalence is probably between the ages of 70 and 80, but there is no specific age for late-onset disease. Alright. Well, thanks Lou. Please join me in thanking the speakers and thank you for coming.