How to live longer? Harvard expert Dr. Sinclair explains at #HTLS2020

welcome to the session, dr.

sinclair

, it has been a busy week for you as we know that dr. Sinclair was on the cover of Nature this week. Nature is one of the world's leading scientific journals and was there for its seminal work showing that reversing the biological clock can restore vision and mice with age-related blindness. Now this approach will have profound implications for other age-related diseases and Dr. Sinclair will tell us more about this during the session and apart from that, of course, talk about why we age and why we don't have to do it now, that's really interesting because none of us want to get old anymore and dr.

Sinclair has answered some of these questions in his best-selling book Life, but we're all going to walk away with life hacks at the end of the session, so even if you've read the book stay close and listen to it, so I'll start by inviting Dr. Sinclair to give a presentation and talk about his various advances around aging and at the end we will continue with questions, Dr. Sinclair, thank you very much for having me today. I hope you can. You can see some slides. I'm going to give a brief presentation over the next half hour. more or less and then we'll have some questions.

I'll be happy to answer them so we all know what aging looks like. Basically, our body deteriorates over time, which leads to a variety of diseases and we have been analyzing. aging for thousands of years trying to understand if there is anything we can do about it because the end of life for many of us is not a pleasant thing and it is certainly not something you would want your children to have to worry about if you don't. did. I have to do it and so my quest for the last 25 years, at least professionally, has been to try to understand some of the answers to some really important questions: Why do we age?

Is there anything we can do to stop it? If you reduce it, will you? living a

longer

and, more importantly, healthier life, it's all about health, and finally, a question that we hoped was answered yesterday and that we published in the journal Nature, which I will talk about today is that aging is even reversible, now is a very important moment for the entire planet. to understand aging and the reason is that in 2018, for the first time in the history of our species, the number of people over the age of 65 exceeded the number of people under the age of five and that trend will continue to go in that direction and we are already seeing in many countries around the world that the social and economic burden of caring for older people who are no

longer

productive is an economic burden that is truly crippling and the older the population ages as a percentage, the more difficult it is for young people to take care of your grandparents and your parents, and so what we're trying to do in my lab and I also speak on behalf of about 100 labs around the world doing similar research we're trying to understand if we can compress the last years of life who are sick in a very short period.

In fact, we've been working on animal studies in the lab for at least the last 20 years, showing that we can quite easily extend the lifespan of mice. and the rats and even the dogs, um, and make them

live

healthier until the end, until they die quickly, so that's the goal, it's not really to keep us in nursing homes and be sick longer, not to extend the old age, what we are doing. On the contrary, our goal is to expand youth so that perhaps we can

live

to be 90 or 100 years old and towards the end still be productive members of society and play any sport you want with your rug with your grandchildren and great-grandchildren and this talk to live forever.

It's not really something I care about or am even working on, it's more about how we address the problems we face right now and the money we could save is trillions of dollars every year across the planet in the US. It is estimated that just reducing one of the main diseases to 10 would save at least three trillion dollars in the next decade, so this is real money that we could save and that could be used to address other problems that we have, improve education, combat climate change and other things, and in terms of population growth, most countries are already stabilizing in their population and ultimately the goal would be for the population to stabilize and be replaced by normal levels and you might be thinking well, David, if you slow down aging, we'll be overwhelmed. with people that is not the case, the number of elderly people is not that big, um if you do the math, then let's talk about medicine and what the future will be like in the near future and also um estrada said I will talk about what we can do each one in our daily lives to have the best possible healthy life expectancy.

So I work in aging and the problem is that there are a lot of companies on the Internet and a lot of people who don't really have a degree in in this field who claim that they have, quote, unquote, solved aging drink this eat this antioxidant and the problem is that It is very difficult to know what is real science and what is not and there is such a big difference between 99 of what exists is mostly incorrect or exaggerated compared to what we do in my laboratory and my colleagues, as I mentioned on the cover of the major scientific journals and even two Nobel Prizes have been awarded for relevant or study-based research on aging, so talk about what is really real and what could really work and cut out all the other noise, so this is a graph Interesting thing I wanted to share with you.

We often think that we have reached our maximum life expectancy as a society. The graph shows that this is not true. What is represented here is the country with the maximum life expectancy, uh, the longest life expectancy. Well, at first there was Australia, where I came from for a while, but now it's Japan that has the longest average. life expectancy and what you can see in this graph is that throughout the 20th century and up to today there is a very linear and predictable increase in human longevity and each time these groups that you can see on the right have said: " Okay, we've peaked, we've broken through that glass ceiling and we're still adding years to life, but not all of them are healthy years, we're very good at preventing heart disease, we can lower blood pressure, cholesterol, medications have had a great success, we have heart surgery, so we tend not to die as much as before from cardiac reasons, but the brain still ages at a normal rate and we don't do much about it, so we end up with increased dementia and one of That is Alzheimer's disease, so our focus is to treat the whole body with medications and lifestyles that will keep every part of the body healthier and younger, which is why today most developed countries have a life expectancy of between seven years, seventy and eighty years, which is certainly much better than that.

It was a hundred years ago and none of us would go back to those days before antibiotics and the average life expectancy was, you know, 65 70 and we would retire and die a few years later. We are on track to have a couple of scenarios, one is that we will live longer but we will still spend a large percentage of our lives in decline and sick with many diseases and being frail. The other alternative that is in the background if we are successful with this research is that we will live. longer and healthier and that sick part of our lives will be much shorter, so every time I talk to politicians or business leaders or even people I know I won't say on the street because we're in a pandemic, but most people You think of aging as something very different from cancer, heart disease and Alzheimer's, but in reality that is not the case, aging is nothing special, in fact, aging is by far the main cause of all diseases .

Well, not all, but most of the major diseases. on the planet and because we've gotten rid of all the easy things, we've greatly improved child survival in middle age, we tend to do pretty well, but it's the end of life where we haven't been successful and as I, I mentioned that the main reason is that we have only been addressing one disease at a time and to live substantially healthier and longer it is necessary to address aging itself, which drives these diseases. Last year, the world health organization approved or announced that they would declare aging. as a disease, a treatable medical condition, so why is it so important?

One is that maybe federal agencies, governments will change the law so that the doctor can treat aging right now, if there is a drug and we think there may already be some drugs. approved for other diseases, could extend life expectancy at this time. Your doctor may do this, but typically does not prescribe these medications for your long-term health unless you are already sick. An example of such a medication is first-line metformin, often the first medication given to a patient. type 2 diabetic with high blood sugar, but by looking at tens of thousands of people who have taken metformin there is a lot of evidence that they are also protected against brittle cancer and Alzheimer's disease, among other things, but your doctor You cannot normally prescribe metformin now.

There are some countries where metformin is available without a prescription, which I think is a good thing because it is a very safe medication, but here in the United States, for example, it is largely inaccessible unless you already have type 2 diabetes, the another reason to declare aging. a disease that is important is that it would lead to greater investment in research and development of drugs to treat and prevent these diseases. I mean, if you're biologically 30 years old, even if you have 50 birthday candles, you're much less likely to get cancer or die from a heart attack and you might say well, how would I know if I'm turning 50?

How old am I? I'll tell you in a minute that we can now measure very accurately, with an error of less than five percent, how old are you really? Not by how many times the Earth has gone around the Sun, so what I'm going to do in the next 20 minutes is tell you, really, what happens during aging. We thought: can we stop it and reverse it? About 10 years ago, well, seven, if you follow this article, I show you the number of us, as researchers in the field of aging, declared that we had discovered what we thought were the most important causes of aging itself and there.

There are about eight or nine of these things that happen to us as we get older and hopefully you can read them, but there are things like DNA damage, the loss of the ends of chromosomes here called telomeres, there's a detection of dysregulated nutrients, so getting diabetes mitochondrial dysfunction mitochondria are often referred to as the batteries of our cells, they give us energy without mitochondria, we would all be dead in about 30 seconds or less, it's like taking cyanide, cellular senescence, here it is shows with this sheet what that really means is that there are cells in our body that act like zombies and the older we get, the more they accumulate in our body and seem to cause cancer, diabetes and other problems during aging and there are many scientists who are working On it.

This in the hope that one day we can kill those cells and that the body can be healthier. Other things include stem cell depletion and we lose the ability for parts of our body to communicate with each other. The brain tells the body to be young. and some organs, like the liver, will also tell the rest of the body to be young and we lose that communication too, but what I want to talk about today is a new area that is really emerging as one of the main causes of aging and the reason it's exciting is that it looks like it could be reversible and that's this one here in darker green that's written here as epigenetic alterations essentially epigenetics is the description of how our body turns genes on and off and for each cell we need a different one. pattern of which of the 25,000 genes are turned on or off and what we find is that in the young the cells are wonderfully controlled if the genes are a piano, they play perfectly in a concert, but as we get older what we see is that the pianist is making mistakes and hitting the wrong keys and it's starting to sound like a terrible cacophony of sound and if you're listening to this you probably want to put your fingers in your ears, what we're looking at is trying to understand what drives that process what makes the cell read the wrong genes as we age and is it possible to do a reset can you get the pianist to play the beautiful music of youth and as you will see I think theanswer could be yes?

So this all started with what I call the information theory of aging, essentially when we are born or even when we are fertilized like an egg into a sperm. There is information there. Now there are two types of information in our bodies, mainly one is the genetic information encoded by our DNA, we call this the genome and we hear about it quite often in the news and it has led to a revolution in biology, of course, our ability to read the genome now is quite dramatic. A student in my lab could read her genome. In just a couple of days on a device that looks that size, we've gone from a billion dollars to a couple hundred dollars to read a human genome, that's one type of information, the other type is DNA regulators. , the genetic.

The regulators that I just described make up the epigenome and these are mainly proteins and chemical modifications of those proteins and also chemical changes in the DNA. These are very important because every cell has essentially the same DNA. So how do we have brain cells? Do we have skin cells? It is the epigenome, the pattern of which genes are on and off that determines which cells will become skin and which cells will become nerves and that pattern must be maintained in some people for more than 100 years. The problem is that it doesn't hold up perfectly, so a good analogy is a CD or DVD.

For those under 20, I should explain what we used to use. However, these for storing music are a good analogy because the information on these discs lasts for many years, probably a hundred years if you take care of it, but these things used to get scratched pretty easily and when they get scratched the player wouldn't work very well and This is similar to what happens to our DNA, so the DNA would be the music and the scratches would be the epigenome, the inability to read it and the question we've had is how do these work? Scratches occur and can you polish those records to get the beautiful music back?

This is more similar to what is really happening to you. This is the nucleus of a cell on the left. A young cell. The genes are these red dots that you read here. This is the RNA that comes. outside the gene and this line, these loops are the chromosomes and you can see that some genes are in the red dot and some genes are kept away by bundling the DNA into these protein bundles, we call it chromatin, which happens over time and we know it. What is certain is that this beautiful pattern in a young cell that gives the cell identity and function will be lost over time, so now the old cell is turning on genes that were previously turned off and vice versa, and these old cells do not function very good. and we think that giving rise to disease, wouldn't it be something if there was a memory of this pattern that could be reset so that you could take a complex tissue like the eye and reprogram it, hit a reset switch to turn it into young tissue? again so that it heals and functions as if it were young again and when we are young again one of the things that we have discovered is DNA damage and the process of repairing that damage drives this epigenetic change, this epigenetic noise that You can call it and Anyone who has spent a lot of time in the sun will know that DNA damage will cause aging and we believe that this is the main reason, not so much genetic changes, not mutations, but epigenetic changes, which is good. news because if we have many mutations in our cells and we lose the DNA sequence, the genetic information is extremely difficult to restore and find again, in fact, once all copies of the genes or two copies have been lost in most cells. once you've lost it you can't get it back without some very complicated technology but if it's just the regulation of those genes then you can imagine you can restore them so this is good news so DNA of course , it's not floating around ourselves, but it's six feet long in each cell it has to be packaged very tightly but also very precisely and this is nylon, but it refers to the DNA as this cord and we have these proteins called histones in which is the DNA wrapped and where it is wrapped.

Very tightly packed into these bundles, the genes are turned off and when they are turned off, those genes become accessible to proteins to read them and read the gene and that's how our cells control which genes are tightly packed and turned off and which ones are turned on and so Of course, this happens all the time, every time you have a memory or eat a food, the cells will respond and change the genes that are on and off, but not as much as you might think because if you change the structure too much, the cell could become a cancer cell or could age, mainly what happens is that these bundles stay the same throughout life until you age and there are some processes that control one of these processes is called methylation.

Methyl is just one type of chemical, it is a carbon atom. with three hydrogens and the cell binds these methyl chemicals to the DNA and to these proteins that package histones and that helps establish which genes will remain turned off and which will be activated. Interestingly, these so-called methylation patterns while beautifully organized when we're young, they change in predictable ways as we get older and as I'll show you, we can use these patterns like a clock, so here's an example of that. Well, on the left y-axis is the biological age in years and at the bottom.

It's chronological age, then your birthday candles and what the field has discovered. I must give credit to my colleague Stephen Horobak. We sometimes call it Horvath's clock. What we have seen is that these changes in these methyl groups in DNA can be read. by a student very quickly it can take you know it's a couple of days to get the answer some people typically those people who have bad genes or haven't taken care of their bodies will be older than their actual biochronological age some people I will be average and some people will actually be 10 to 20 years younger than the average person at that same age and it is known that those people who are biologically younger are healthier and live longer than those who are already accelerated, so in other words, you could take a sample of blood from you today and then in a couple of days it could tell you when you are likely to die with fairly high accuracy.

That's important because, first of all, it can tell you if you need to take action and if you really need to pay attention. to your lifestyle or your genes, but it also allows us to quickly establish whether we can slow down or reverse the aging process in both mice and humans and there is already some evidence that we can not only slow down this clock, but reverse it in both. in mice, as I'll show you, and recently Stephen Horvath published that he was able to give a cocktail of molecules to some people and reverse this clock a little bit in just two years, but it's a good starting point, so it's a very good starting point. departure. important development: we can accurately measure age, so what about reset?

Wouldn't it be great if we could take a pill or receive an injection that would remind our tissues and organs how to become young again, the skin would heal, wrinkles could disappear, and diseases could disappear? reverting this is the equivalent of polishing that disk so that we can recover the youthful information so how could we do this? Basically what I'm saying is that there is a backup copy of the juvenile epigenome in the body and that maybe we could use it to reset the cell now we didn't know until well this year in our lab if this was possible, but we were hoping it would be possible based on in a couple of observations, first of all, you can take a tadpole, um, it was a typol or I think it was a tadpole, a cell and put it in a frog egg and it regenerated a new organism.

John Gordon discovered it and won the Nobel Prize for it. The other thing we can do today is clone. animals in depth, the sheep was the first but now there are many different species that have been cloned and live, although you may not realize it, these animals live normal healthy lives even though Dolly was an aberration, what does it say that? There's probably a reboot. change, you can start life from scratch, but can we do this in a living organism? Can we take a mouse and reset it? Can we take a human and reset the body to be young?

That's what we're working on. The equivalent would be to take our DNA that has now lost all its beautiful organization and put it back into this structure, so we started working on this about four or five years ago and we had a big breakthrough in the last few years: a student of mine found a combination of genes. that could really do this, the combination of genes that are normally only activated in very young embryos and babies, so I already mentioned that we can generate new life from nuclear cloning and we can generate new animals, what we can also do is take adult cells and convert them into stem cells, this is called reprogramming, we also know that there are other species, like this marine organism called hydra, which can regenerate two individuals from one, there are some species, salamanders, axolotls, um, you can even cut it the tip of the finger to a mouse.

It will grow back and in our bodies, if you cut off a large part of the liver, it will grow back. These are all signs that it is really possible to do incredible things with ourselves in terms of aging and regeneration, so I mentioned that John Gordon won the Nobel. prize for his experiment with the tadpole the man on the right shinya yamanaka a very famous professor from Japan here who just won the nobel prize in sweden um what he won the prize for was for showing that you could take skin cells from adults or any type of cell you would like. wanted from an adult and turn it into what is called a pluripotent stem cell, a cell that could become any other type of cell, essentially erasing the identity of the cell so that the cell was no longer a skin cell, it could become into anything else and the way he did it was he took a normal cell and in the dish, not in an animal, but in a dish, he put a combination of four genes that would normally be activated in embryos in eggs when they are fertilized and he got These stem cells that are now used in medicine applied to people trying to improve brain function in other organs, these genes encode what are called transcription factors that are actually simply genetic regulators that bind to genes and turn them on and off. , so this was certainly worthy of a Nobel Prize, but the question we had was: can some of these young embryonic genes be used to reverse aging without causing them to become stem cells?

The last thing we want is to create stem cells in the body because if a cell does not have any identity, being a tumor, it can grow and, in fact, if you activate these four genes in a mouse, when it is older it will develop cancer and in some cases kill to the animal that other laboratories have shown, so this was a very risky experiment, but What we did was look at the cells how to activate some of these genes and we found a unique combination that worked to reverse the age of the cells by up to half, but not completely.

The way we did it was we took a virus, not a dangerous virus, these are. Domesticated viruses that are currently used for gene therapy in people, for example to repair genetic defects in the eye and restore their vision, and they are called Aav, so we packaged some genes into this Aav and tested if it could reverse the age of the cells. now we chose neurons in this case in the back of the eye of a mouse we wanted to see if we could make those nerves healthier now in a young mouse these nerves will grow back the video unfortunately doesn't play but this would be a nerve that It grows on the plate and it does not grow if you damage an adult nerve it will not grow back.

I think we all know that if you damage your spine or damage your optic nerve or your brain, it won't miraculously grow back, but it does if it's very young, so we thought if we could reprogram these nerves in the eye to be very Young people, we could get a better repair and maybe even get those mice's vision back. Now, this was an optic nerve where it was uh, these nerves are not healthy, if they are healthy they glow orange, but here you can see that most of these optic nerves in the mouse have died now if we apply three of the yamanaka genes from the that I spoke to you, called or yes. and k and we turn them on for three weeks those nerves grow back, you can see that many of them are preserved, the eye is here, the brain is on the left and they grow back, this has never been seen to this degree and certainly has not been seen. when the treatment was given after the cells had already been damaged and we call this epigenetic reprogramming and these nerves when they were damaged aged prematurely and died perhaps of old age in a matter of weeks and here these nerves came backto be young, so we can also test vision in this experiment we are testing glaucoma.

You may have family members who have glaucoma. Pressure in the eye is one of the biggest causes of blindness on the planet. And if you lose vision due to pressure in your eye, you never will. to get it back there is nothing you can do except some medications that slightly slow the progression of the disease, but we asked if we have a mouse that has lost vision due to pressure, can we restore that vision and can we test this in several ways? we can observe the electrical signals in the eye but another way to do it is to observe vision and here is an experiment where the mouse observes moving lines, the lines move like this and if the mouse can't see it will just stay there , but if you can see, you will move your head like this and we can track it with a camera and this experiment here we just need to focus on the red versus the blue and what you can see is that with our reprogramming we get the youth back. cells and we also recovered some of the vision that was being lost, so this is the first time that we have been able to restore vision in blind mice or at least in mice that have lost vision, but then we did something interesting.

We partnered with another lab at Harvard that works on vision and we took just old, normal mice that were in the lab and living normally and put them in front of the screen. Could you ignore it? This is just the The mouse is a little jittery on the platform down here, but you can see this mouse doesn't move its head, this mouse can't see because it's old, it's about a year old and this type of mouse loses its vision quickly because to our old age. What we wanted to do was deliver our three-gene combination with the virus into the eye.

It is very simple, in fact, it is not difficult. Doctors do this all the time. They give a single injection into the eye of people who have, for example, macular degeneration, and it is painless and very fast. We did it. The same thing for the mouse did not feel it and three weeks later, after we activated these epigenetic reprogramming factors, we obtained this result. We had old mice that could see. It can be said that this mouse can now see again and, in fact, these old ones. The mice on average could see as well as young mice, which to me is really amazing that we can now restore vision in blind mice.

My student at the time is called Juan Chen Liu, he is now a postdoctoral researcher or PhD adopter, he said. the cells in the back of the eye and measured whether they were younger and, in fact, it turns out that they were much younger according to this clock and not just that this, uh, this symphony that I was referring to where the genes are played , was once again a beautiful youthful symphony of genes, in which the genes that were turned off with aging returned. In other words, we had restored the identity of the nerve cells. Nerve cells woke up from sleep in the old mice to function as if they were young again.

In fact, literally, we were young again and we really know that this clock is important or at least that methylation, those changes in DNA are important because if we block the eye from eliminating those chemicals, vision is not restored, so that this watch that I'm telling you about those chemicals. They seem to be important to the aging process and the reset switch which we didn't know about until we discovered this recently. One way to think about this is that if you have a clock on your wall, you know if you turn the hands of the clock back nothing is going to change because the clock is just a clock, but what this experiment tells us is that this is a clock. very special watch if you move the hands back time goes back age goes back yeah I just want to um We talked a little bit about what we can do in our daily lives to be as healthy as possible in old age and we know that the way we live our lives has a huge impact on us, in fact, most of our longevity and health 80 is in fact determined by our epigenome, not our DNA, and we can change our epigenome based on the way we live, so what can you Do you do well now if you are getting enough food, if you are eating three regular meals a day, breakfast, lunch and dinner, or even eating snacks?

In the middle we know that that's not going to give the best chances for longevity and certainly overeating will be even worse, so what I do is skip at least one meal a day, we don't have enough food in our home and our meals tend to be For starters, be big and try not to snack. I like to drink tea and coffee. If I'm a little hungry and you get used to it, you might not want to skip breakfast. You might want to skip lunch. Skipping dinner is different for each individual. I also want to point out that if you are young, in your teens or 20s, this is probably not for you.

I'm talking more about middle-aged people. older people whose metabolism has slowed down and we certainly don't want to suggest malnutrition or starvation as some way to improve health, that's the last thing we want to talk about or imply that that might be helpful, it's more about being um, you know, at least part of the day a little bit hungry and we know we've known this for thousands of years that this is actually helpful, what we didn't realize was that what happens when you're hungry is that these longevity defenses, these longevity factors that I am describing to you and others are activated if we sit all day if we are always eating or do not feel hungry, our bodies will relax and will not fight against aging, so this is one way to activate those defenses against aging uh, get some exercise, get out of breath a couple of times a week if you can, if you're not moving, get up, walk at least, um, also lift some weights, at least once a week.

I try to lift something, um, I also struggle a little with our sun, that helps me, I talk about the hip hinge exercise, this is bending at the hips and lifting weights, it's very important especially to keep the hips strong so they don't walk Don't even bend, because in the US alone every 19 seconds someone falls and breaks a bone and this is as bad as having cancer in terms of survival. You may want to talk to your doctor and get tested to see what is working in your body and try to counteract what you can. I also have devices on your wrist that can tell you how you are doing and I do that because I don't do blood tests often, but I try to monitor how I am to see if things are okay. work sleep well reduce stress all of this is important sleep is actually closely linked to these longevity genes that control the rate of aging and here's one that you may not have heard uh you want to eat plants that have been stressed what do I mean by that Red Well Wine is an example of a food made from grapes that have been stressed.

You'll probably want to eat plants that have been grown outdoors or dehydrated, and in fact we farmers know that if you stress plants before harvesting them, like orange trees, you can put a clove in the stem and it will produce better fruit. The reason is that plants produce their own molecules to improve survival and longevity and we believe and have a lot of evidence that when you eat those molecules from food you mimic exercise. And you imitate fasting and hunger. We call this zero hormesis. So I've given you a lot to think about today. You can read about the new discovery online at Nature.com.

It's available right now. I have tweeted about him. There is a free copy if you want to download it if you don't have a subscription to Nature magazine and in my book Lifespan I talk not only about why we age but what we can do about it in much more detail than I told you. about today, including what I and my family do, and my dad is 81, disease-free and in perfect health and is literally stronger and fitter and possibly happier than me, so it's not a clinical trial, but it is a ray of hope for everyone. of us uh and I want it there um now we can answer questions and you know, thank you again for inviting me here today, thank you dr.

sinclair

and I want to start by asking you if we are likely to receive a pill or a vaccine that can actually reverse aging in our lifetime when I say lifetime I mean the next 20 to 30 years.

Well, I certainly hope so. I don't have a crystal ball, but we're working here in Boston to take this reprogramming technology, which I showed. for today for the eye and in the next two years we hope to treat the first glaucoma patient to see if we can restore vision and yes, I mean that's just one example of at least 20 companies that are working on drugs that should, yes everything works slowly and maybe even reverses aging, so if it doesn't happen in the next 30 years, something must have gone terribly wrong, right? This epigenetic programming that you talked about, how often can it be done?

Can you do it just once in your life? a lifetime or you can do it repeatedly yeah that's the big question we're working on we've only done it once but maybe you can do it ten times maybe a hundred this is a really interesting question I think we can do it . several times there's no reason I can think it couldn't be done repeatedly, so you know, imagine with me for a second that we could find a pill or a gene therapy, a virus that would do what we did to the mouse's eye , but throughout the body and we have already designed this to be activated with a pill.

We used a molecule in those mice called doxycycline, which is just an antibiotic. It's not the fact that it's an antibiotic that's important, it's just a molecule that I can give it to mice as a drink and it activates the genes, so one day maybe you go to the doctor, they give you an injection and they give you a pill For three weeks, you will rejuvenate the whole body, improve memory, improve eyesight. better healing maybe even looks better and then 10 years later you go back and take another treatment with that drug for three weeks so that this epigenetics resets again.

Can they be used to treat diseases other than glaucoma? I mean, what would you think? What are the projections? What is the potential? Yes, some other colleagues in my field have shown that aging can be reversed in the brain and my lab is now working on this. We're actually growing little brains in the lab. Many brains can now develop. of people's cells, these are reprogrammed cells, we are not taking brains out of people, but now we are looking to reverse the age of the brain, maybe we can treat Alzheimer's and dementias that way, but they have also shown internal problems.

Organs can be reversed, the kidney, the pancreas, I mean ultimately any part of the body that we believe can theoretically be reversed, even the joints. Joint pain is a big problem and maybe we can get those joints to heal and grow back like the young women you mentioned in your presentation that there is a lot of dubious science on the internet, so there is so much information that you don't know, so What does real science say about supplements, what are the supplements that work and what are the supplements that don't? Do you recommend it, oh well I can't recommend anything because I'm fine, what would you take yourself?

Yeah, well, I've always tried to be honest about this. There are many supplements that have not been shown. doing something on people who could have been shown with a mouse to do something doesn't mean they don't do anything, but there are often claims on the internet that they do or at least that they say they work, but No, well, first of all Firstly, what I would say is to go with a company that has a good reputation. If you want to pick a supplement, there is a term, at least in the US, not sure globally it's called gmp. good manufacturing practices and that's good, that at least means that they are following the guidelines set by governments to produce good products, go for the very pure molecules, which often supplements are 50 percent, this 10 percent I prefer to get the 98 or more pure supplements.

We have been working with resveratrol for many years. The molecules in red wine are called resveratrol. There are some pure versions of that that you can buy over the counter or online. I have been taking resveratrol for a long time. I think after 15 years I'm still doing well. There have been clinical trials, some that showed no effects, some that showed positive effects. It depends on how it is administered. If you take it, you'll want to eat it with some. food or some yogurt, for example, so that it is absorbed, so resveratrol is one. There is also something else in the body called nad nad capital nad which is a molecule that we need for life, without it we would be dead very quickly and as we age what we see is that our bodies produce less nad and there are supplements that can be obtain in pure form they increase the idea of ​​raising NAD levels.

Now we don't have much information about that in humans yet. There are a couple of studies that haveshown that they appear to be safe, at least so far, and that there is a disease called also known as Lou Gehrig's disease, which is a neurological disease where patients did better with nad-stimulating molecules. but it's still early for that, in general, you know there are things you can do, there is vitamin D, which of course is very useful, and some other supplements for vitamin deficiencies, but apart from that, the really important ones are foods and the exercise. Until we have these medications they seem to be the best option, so would you recommend a low carb vegetarian diet or do you eat meat?

What is the recommendation? Indians are largely vegetarian, so yeah, it's great, here in the US there is too much meat. we have everything fried so that doesn't help, but anyway, well that's not great, but there's also this carnivore movement in the US where people are promoting almost pure meat diets, there's not much evidence of that is so high. Meat levels will be good for you in the long term, in the short term, yes, sure you could build a little more muscle, but in the long term, vegetarian diets are definitely the way to go. Personally, I eat a pretty healthy regular Western diet, so unfortunately there is meat in a lot of the meals we eat as a family, of course our kids need meat to grow, but yes, I try to focus on salads and vegetables as much as I can, so you want your diet to be more like uh what. everyone would eat a rabbit instead of a lion, right, you are getting a lot of questions.

There is a question from Ananya who wants to know what are the most interesting anti-aging tools or technology or recent discoveries that are out there right now. Yes, good. I'm excited about reprogramming to be able to reset the body, which is obviously at the forefront, but there are also other technologies that are exciting, one of them being the ability to activate the body's natural defenses against aging, so there are certainties. where I work, you kindly mentioned them before, we have seven sirtuins in the body, they are found in most of our cells and they need this molecule and so the ability to activate those sirtuins is an exciting area that resveratrol looks at. to do that. boosters seem to do that, so that's one area, the other area is called cenolytic, these are drugs or molecules in development that eliminate those senescent cells that I talked about earlier, those zombie cells that accumulate and seem to contribute to aging and to cancer.

That's also a super exciting and relatively new area, and lastly, a new area that's pretty exciting is taking drugs that are already available, like metformin, and there's another one that's not as safe called rapamycin, which is used for immune suppression and it seems to do wonderful things. to mice and looking at people they also seem to have effects on slowing aging and even reversing it, so that's also promising when you ask me how soon until we have an anti-aging drug is possible. We already have one. or two available, we just need to have more evidence that they actually work the way we expect.

I use a combination of medications that can likely work together to address different aspects of aging. I have a question from Amman that says In your book you state that there is no biological law that says we must age. What do you mean by that? I mean we all grew up. You know they tell you that aging is inevitable and that we will all get older, so you are defying it. Okay, yes. Why should we simply say that something is inevitable? 100 years ago dying from cancer was inevitable if you had a tumor, there was very little you could do and we decided that we are going to fight cancer, heart disease and Alzheimer's disease, so why? aging, which is the driving force of most of these diseases, why is aging something we should accept?

It is quite the opposite, because it is common and just because something is natural does not mean we should accept it. There is nothing in the natural world that we accept. We accept that we have been since we took a stone as a tool and lit a fire to cook food, we have essentially been changing the world around us and aging should be no exception. Now I agree with you that this aging is going to This happens, we are not going to live forever, but can and should we try to live another 5, 10 or 20 more years in a healthy way, absolutely the same way we did during the life in the 20th century?

How long could we live well? There are species. on our planet that live thousands of years there are even mammals whales that can live hundreds of years so it is feasible there is no law that says we could not live longer and we are finally being understood being able to understand how these other animals we are capable of living a long time more than us is like what you said before, it is not only about living longer but also about living a healthy life because we have more and more studies that have shown that, although people live longer, they are disabled and it is not a healthy life that It's going to be the extra 20 to 30 years, so I have a question from Deepika who wants to know when the anti-aging intervention would start.

Is there an optional age to start? So, of course, this is input intrinsic forensics. So they're both fine, so I'm extrapolating from the hundreds of animal studies that have been done, from fruit flies to small worms, to mice, and even dogs and some studies with monkeys, so we have a great base of data to extract information, but we don't have it. I know about humans, I would say that in my scientific opinion, around the age of 30, aging starts to set in and actually causes your system to not function very well, you start to slow down with healing in sports, so I myself started taking resveratrol when I was 34 years old. and I'm still fine, I'm still alive, it doesn't seem to hurt and it's not very expensive, so the trade-off is such that when I was 30 it was worth trying and certainly now that I'm 50 it's definitely something worth trying, think about this , we know what will happen to all of us if we don't do anything, as long as it's safe and doesn't affect your budget, I think, especially the older you get, the more it's worth it.

It's trying some things, but it's all individual. I would say that if you're in your 20s, there's very little reason to do anything other than eat healthy and exercise, but that's the best advice. A couple of glasses of wine would also work. Well, that's up for debate, I think any doctor would say that in moderation, a glass of red wine a day will probably do you some good. You don't want to overdo it, of course, alcohol will ruin your liver in the long run, but there are many healthy molecules in red wine are resveratrol, but there are many others that come from grapes that are preserved in wine and I think that's one of The main reasons why red wine is so healthy, but how long should you drink it or drink it?

For red wine to take effect, it would probably take about a decade, that would be a minimum. The reason is that red wine doesn't contain much resveratrol, maybe one milligram, and in our studies we give mice the equivalent of a hundred to two. a hundred glasses a day very drunk, so yes, luckily it's in a pill or in your food, but yes, I don't recommend drinking that much. I have a question from Justwant, who wants to know what exactly the information theory of aging is? Could you give me more details? A little bit about that, yeah, yeah, so this is the theory that largely came out of my lab and that is that we lose genetic and epigenetic information in the form of DNA and the three-dimensional structures of the DNA, the genome and the epigenome.

If any of you are interested in information, whether it is computer information, radio signals or photographs, you know that digital information is the best form of information storage and DNA, the genome is digital instead of ones and zeros, It is an action of the chemicals that make up the DNA code. and for that reason DNA is very stable and robust. You can boil DNA in the lab and it's fine and for the most part our genome is intact even when we're 70 or 80 years old. But the epigenome is not digital, it is analog, it is like the equivalent of a cassette. tape and it will degrade over time and it is the loss of the analog information, the epigenetic information, what we believe and we are showing in articles like this one that we published yesterday in Nature, that it is the loss of epigenetic inflammation that is the main cause of aging, thank you .

Thank you very much, I think we are running out of time, the future seems very young thanks to scientists like you and thank you for joining us.