Can we live past 120 years?

speaker: Ronjon Nag

video: https://www.youtube.com/watch?v=ZJ5UuU7PAhc

date: 2023-05-03

LLM-generated summary: Professor Ranjan Nag delivers a comprehensive lecture on the biology of aging, framing it as a potentially treatable condition akin to a disease, evidenced by supercentenarians like Jeanne Calment (122 years) and current records around 115-117 years. He traces historical lifespan gains to low-hanging socioeconomic fruits (nutrition, sanitation, antibiotics) rather than biology alone, projecting demographic shifts toward more centenarians and invoking "?longevity escape velocity"—incremental 20-year life extensions via emerging tech to outpace mortality. Distinguishing chronological from biological age (via VO2 max, max heart rate, epigenetic clocks like methylation assays, grip strength, one-leg balance), he estimates genetics at 20-30% influence versus dominant lifestyle/epigenetic factors, urging separation of confounders in causation-correlation debates. Critiquing interventions (supplements like NMN/NAD+ show weak evidence; metformin/rapamycin have trade-offs like reversed exercise benefits), he endorses exercise (molecular mimics in development), intermittent fasting (autophagy targeting senescent cells), personalized strategies (ageotypes: kidney/heart/immune dominant; glucotypes via continuous monitors), and biotech frontiers (senolytics, parabiosis, thymus regeneration, mitochondrial transfer/rejuvenation, epigenetic reprogramming, AI-driven drug repurposing from existing libraries to boost success from 1/20 to higher odds). AI and robotics promise healthspan extension via predictive biomarkers and assistance, prioritizing quality over mere lifespan amid ethical/population concerns, with cryopreservation/mind uploading as speculative Plan C.

Speaker Introduction

Okay, now let's get to the actual talk of today. Let me introduce Professor Ranjan Nag. So Professor Ranjan Nag is an inventor, a teacher, an entrepreneur, and he's got his PhD from Cambridge. He has a master's from MIT, and he's an undergraduate from Birmingham University.

So, coming to this talk today is, is aging another disease that ultimately needs to be cured? This evening, Ranjan will delve into the biology of aging and discuss what age-related diseases actually are. Can lifespan be extended and are centenarians any different? He'll also explore how AI can create robotic and software assistance to improve the quality of life as we age and is living past 120 or even possible in any form.

Can I invite Ranjan to the stage, please? Thank you.

Talk Opening and Historical Context

Thank you. Perfect. Excellent. Is the audio working? Yeah, great.

Thank you very much for that very kind introduction, Clive. It's great to be here. I'm normally in Palo Alto, California, but it's great to be here at the IET. And I still work on AI, and this is an article that came out. It didn't come out three weeks ago but it came out 30 years ago almost exactly 30 years ago and we're still talking about it just as an emphasis to emphasize the point that these fields often are longer than we think and even in the field of neural networks and longevity people have really been thinking about these things for about 80 years or so and some of the first ideas.

Audience Poll on Extreme Longevity

Okay let go back to this question who would like to live longer than 120 maybe this is like a self audience though right it sort of and who wouldn't like to live to 120 okay there's a whole load of people who are not answering that question we've we've got a lot to get through otherwise we'd love to get get to the discussion why why why live longer or why not and so the question is can you actually live longer than 120 and the answer is clearly yes because somebody's actually done it.

Supercentenarians and Healthspan

This is Jeanne Calment she lasted 122 years 122 and a half years a French lady and uh the really question is not can uh can you live till 120 but can you live till 120 healthily because somebody's actually done it and we'll go into why that might be possible and what the obstacles we're looking at.

The oldest living person today is only 115. I actually have to change this deck every time I give a talk like this because people keep passing away. So it used to be 117, the oldest person. This is Maria Branyas Morera. She was born in San Francisco, so not one of these blue zones that are regarded as healthy living places like Okinawa, Sardinia, Costa Rica or Loma Linda California but she uh tweeted or maybe someone tweeted for her you know i may be old but i'm not an idiot so you can still be quite sparky as you get to live longer and that's the trick we don't want to just live longer for its own sake we don't want to be misery for the last 20 years we the real thing is living longer healthily.

Demographic Trends in Aging

Now what's happening today this is 1950 population chart of different age ranges so at the bottom is when younger age ranges and as we get to the top there's much fewer older people so we're not too much different to that but if we play this forward we're going to have a lot more people living to to their older age.

Certainly in Japan, they used to get a silver medal when you reached 100. They've stopped doing that because it costs too much. I think the royal family is still sending out birthday cards if you reach 100 but you have to request it now i guess they don have the databases that match the death registries with the tax records.

Historical Gains in Lifespan

And so the question is we've been living longer for the last uh you know 70 80 years and why are we living longer and the main reasons are the low-hanging fruit uh we make a lot more food no one's starving as much most of us 200 years ago would have been working in farms now hardly any of us work on farms it cost less used to be 50% of our income now it's only 10% of our income and we've got these technologies electricity refrigeration health systems antibiotics people have been educated and so we've been slowly slowly but surely, every year, adding a few years to our age.

And the question is, can we actually get to an older age? Would Stone Age man, where the average age was 18, 20, would he live to 76, which is the average age for men in the United States?

Projections and Longevity Escape Velocity

And so you're getting covers like this. So those of you who've got kids or grandkids, I would put it they probably will live to 120 easily those of you at my age now I ran a marathon three weeks ago so I think you know to be able to talk about longevity I actually have to be younger so I have to keep running these marathons but over time people have been living longer each cohort and the question is can we actually live to 120 and can we live longer than 120 what we have to do to get that so the average age of death is 76 for men it used to be 78 in america which dropped over the last few years um so it's actually been dropped because of the pandemic opioid crisis do we actually have to get another 40 years do we need technology for another 40 years well the answer is not necessarily there's a concept known as longevity escape velocity we don't actually have to get another 40 years we just have to get another 20 years.

And the idea is within those 20 years, we can come up with an innovation to get another 20 years of life. And so I'm at 60, I'm borderline. Can we get an innovation to get another 20 years after that? And then when you get another 20 years after that is there another innovation Is there a drug that we can invent to get another 20 years You don actually have to go all the way to inventing living forever You just have to get jumps of 20 years at a time.

Complexity of Human Aging

Now the problem is we have a very complex system The human body is very complex. There's 78 organs, and they all age differently. And some of these organs, we don't have to worry about as much now if my skin gets a bit wrinkly even though i can run a marathon i still look old that's the problem and uh but i can if i'm wrinkly i can still live a longer time but there's a few five or six organs we cannot do without so clearly the brain is uh one of them heart liver uh if we lose a function of any of those then everything falls apart And so we want to age gracefully.

Chronological vs. Biological Age

And there's a couple of concepts out there, chronological age and biological age. So chronological age is just simply the number of days you've been on the planet. No debate about that. You just count your birthdays and that's it.

Biological age is your actual health adjusted age. Can you run a marathon at age 60? What time can you run a marathon? Mine was 3 hours 37 for those of you who are interested. And so that's not a bad time for a 60-year-old, right? If you have to brag about it, there you go, Sunil's over there. That's roughly his time, he's 20 years younger, right?

And the question is, can we actually keep these human performance measures? And those of you who are athletes who can think about VO2 max, maximum heart rate. Maximum heart rate is a classic formula that says 220 minus your maximum heart rate will give you your age. My maximum heart rate is 201. That says I'm 19 years old. But my running time is close to a 19-year-old.

Genetics vs. Lifestyle Debate

And so the question is, is it all in your genes? How much is it lifestyle and how much is it genetics?

Let me ask you this question. How much is genetics? Let me throw out a question. How much do people think, some put their hand up, how much is genetics and how much is lifestyle? Over there, what? He thinks 50%, any more bids on that? Less or more? It's more lifestyle, less genetic, you don't give a number. It's being, 20% genetics. Anyone else? 60% genetics, 80% genetics. One more bid. 85%.

Okay, here's the answer. So thank you very much, you get the prize. 60, but the articles are pretty wide though, the data, but people used to think it was 80%. And we at the time we'll talk about causation and correlation. Why did people think it was 80%? Because somebody would say, say, well, my parents lived to the 103, so I'm fine, it's genetics. So tell me about your parents. Okay, your parents lived on a farm, they were vegetarians, they were Buddhists. Okay, what about you? Are you vegetarian? Yeah, I'm vegetarian too. Are you Buddhist? No, I'm not Buddhist, but I do meditate, right? Because my parents did. Okay, so what has been transferred? And this is where in mathematics, you've got to separate the confounding variables. What's been transferred is the lifestyle, not the genetics. You could have a debate how much of the genetics is related to the lifestyle, but it's not obvious.

And so this is why people continue the debate and it's lower than you might think. So the good news is, it doesn't matter what your genetics are, we can change it. We can make it, we can address it.

Perceptions of Aging

So what is aging itself? So aging, I ask my students to type it in what they think and depending on whether it's the evening class where we have wide range of ranges or whether it's my student class in the daytime, but this is the evening class and we get nice positive things like wisdom and humor and retrospective and we get negatives of course, we get physiological declines and decline but we got a mixture of positives and negatives So there is a school of thought that you know the younger people are quicker faster etc Sometimes, some of the more recent papers is that they may not actually be more correct. They are maybe quicker, but they give you the wrong answer quicker, right? Whereas as we get older, we give a considered answer. And you can't take away knowledge. The knowledge is still there. you know you get dementia and things but if the knowledge is still there we have different tricks as we get older.

Theories of Aging

So aging is not classified as a disease you can't get reimbursement for a drug for a disease that is not classified as such and so there's two theories of aging one is that there's these hallmarks of aging that cause um age-related diseases as we know as we get older We get sarcopenia in our muscles that get weaker. Stem cells, little kids, when they get scraped, they get heals immediately, no scars, we get older, it takes a few more days. Diabetes is more correlated, cancer is more correlated as we age.

And one theory is we're like cars, the damage theory of aging, we can just fix these bits one at a time and you just get these fixed. The other theory is can we actually find something that actually fixes everything all at once. And as an investor, as a scientist, I look at both theories.

Cellular Interventions: Senolytics and Parabiosis

One theory is if you move old cells, senescence means old. If you move old cells, then mice get younger. And some evidence that if you do that in humans, they get younger as well. And you get nice coats and a theory which is about a hundred year old concept, parabiosis is if you stitch two mice together, an old mouse and a young mouse, so that their blood is shared, miraculously the old mouse gets a bit younger. Unfortunately, the young mouse gets older.

And so I'm not sure if some of you remember, it's probably eight, nine years old now, the Silicon Valley episode of the current's where the entrepreneur has got his young boy walking around with him all the time, ready to transfuse blood to make him younger every time.

Biomarkers and AI Aging Clocks

So people are trying to figure out well what going to actually measure aging And there a concept known as biomarkers And the biomarker ideally should be easy to collect, should be cheap to collect, and should be related to the biological age rather than the chronological age.

The problem is quite difficult to collect because you have to measure it for decades. and it should be able to be reproducible. But people have been trying, people have been doing that and applying AI. This is a site called aging.ai. This told me I was 38, if okay. And you put your blood metrics in and you take them maybe in the yearly physical and it turns out that it's not too bad. It gives you some elements. So my max heart rate measurement told me I was 18. This told me I was 38. Okay. We'll take that too.

Skepticism on Supplements

And so the issue is you can go into Boots or Walmart, Walgreens in the States, and find aisles and aisles of supplements, vitamin C, vitamin D, turmeric, NAD+, NMN. The problem here, again, is going back to that correlation causation. If you get nothing out of this talk, know that the body is complex, and we have to try and tease apart what's occurring.

And you'll read an article that will say, take more vitamin D, take more vitamin C, take more omega-3. And often these articles are not comparing, even though they may have done trials, the trials against the average may be not you. The average person is not particularly healthy. If you are above average, you're doing the right things, doing the diet, doing the exercise, it may not make any difference.

And the question is, we have to figure out how do they know we know they're working? And how do we measure aging? We could actually, one trick is, there's lots of measurements that try to tease apart the training effects with the aging effects. So I just told you I did marathon. So, and I've just called you, my max heart rate goes up. Have I actually got younger or have I just trained and I got better And so there a number of things that people have done that sort of try to tease that apart.

Simple Biological Age Tests

So one of them is standing on one leg with your eyes closed. You have to do it with your eyes closed, because you're standing on one leg for quite a long time with your eyes open. If you do it with eyes closed, I can last about eight seconds, and a younger person can last a bit longer. I won't ask, sometimes I ask you to do it, but we've got so much to get through, I won't ask you to do it.

Another one is a grip strength, right? You can get this machine. It's not very expensive. It's probably about 20 pounds or so. You just grip the strength and measure how strong you are because it's very difficult to train. You're not really training for that. You may be running. You may be playing cricket, but you're not training for the grip strength.

Pharmaceutical Interventions: Critiques

There are drugs out there, metformin, rapamycin. and I'll comment on those because you may have heard about them. The issue of some of these, they do have issues, which is why you see articles that say, well, people who have diabetes live longer than people who don't have diabetes, at least for 70-year-olds. And you tease this apart and say, well, okay, maybe the drug that they're taking, a popular drug, if you have type 2 diabetes is metformin. It's a generic, very cheap. and it's a popular anti-aging drug.

And the issue, though, is it actually making you younger? And again, it goes back to the average person. It might be making the average person because the average person probably does have a propensity to type 2 diabetes as they get older. But the critique is that it reverses the positive effects of exercise, increases inflammation. Of course, some people say, well, let's stop exercise. and take this pill instead. But actually, the logic doesn't quite work there, but it's a good joke.

Rapamycin, again, is another one that's been in the news right now. It's something that reduces aging, but some doctors will prescribe it. But it increases insulin resistance. There is an argument, if you take very small doses, it won't and it'll be fine. But we don't know the numbers yet.

So again, if nothing else you take from this course, this talk, be skeptical of everything you read, hear or see, including from me, by the way.

Calorie Restriction and Intermittent Fasting

Another concept, calorie restriction. This has been known for decades, which is where you just eat less. And again, this has not been really shown quite as strong recently for humans as it used to be. People used to think about it and there's the calorie restriction society that you can actually join and you know the old joke is it you know may you may not live longer but it'll feel like you're living longer.

And so so look at that but people are doing intermittent fasting there is some theories some science around this the theory is that if you stop eating for more than about 15 hours the body will start to eat itself And you might think that's not good, but the theory is it starts to eat the bad cells first, you know, precancerous cells, fat cells. And so this theory of intermittent fasting is basically skipping breakfast, basically, if you do not eat for 15 hours and eat the regular amount of calories, but in a shorter amount of time, it's better for you than eating it regularly. Conversely, there are other people who say the opposite. Pretty much for every theory, there's an opposite theory, but another example.

Stem Cells and Muscle Repair

Stem cells. We gave the example of little babies and toddlers who scrape their knees. Clearly, as we replace ourselves, they're always being replaced all the time, but as we get older, for some reason, they don't replace ourselves with nice, clean, soft, elastic skin, as we do when we're younger.

Muscles, again, the body's miraculous. after you've done a marathon you ache all over and but after a few days we basically you've got you're injured and your muscles look like this this picture of the second one from the from the bottom but then it starts to help it starts to fix itself and in a week or so you're back to normal and back to the near normal muscle but that process does get weaker with age does get less have less integrity.

Exercise and Molecular Mimics

Yeah exercise I a big fan of exercise It solves and affects many aspects of the human body the aging process And why does it do that? I mean, it doesn't just move muscles. It also secretes things. And the theory is that it has great positive effects on the body.

Now, the trick is not to overdo it, because if you get injured, then you can't run for three weeks. and so you get these articles in that story journal the New York Times an hour of running will add seven hours to your life and what's happening here so at Stanford there's a number of projects looking at what is actually happening at the molecular level can we actually replace that exercise dynamic by creating a pill by making the molecules change based on the exercise without actually having to do the exercise. And so the idea is that exercise has an effect on the stem cells, which affects the replacement. There are other theories that we can talk about as well.

Epigenetics and Methylation Clocks

You know, DNA, which is the same in every cell. People are now looking at what we call epigenetic changes in the DNA, the stuff around the DNA, which actually we can stop those changes. The most reliable aging indicator is something called a methylation test, which is methyl groups that wrap around the DNA. And if we can actually stop those changes, can we actually reduce aging?

Cellular Rejuvenation and Thymus Regeneration

The other theory is you've got the things inside your cell. And it turns out if you change four things, then you can actually make the cell younger. I've got a relationship with Rejuvenate Bio. I think Marco's here somewhere. I saw him over there. There he is. Marco, you can go and talk to Marco over there. He'll tell you all about epigenetic reprogramming. We're putting lots of effort to try and change it at the cellular level.

Thymus. Thymus is an organ here that creates your immune system when you're born. And as you get older, it gets, your immune system gets stronger and stronger. But in your late teenage years, your thymus starts to get smaller, which is fine because by the time you got to 20, your immune system's built, you don't need it anymore. But when you 80 you kind of want it back again So there a whole set of labs and companies trying to figure out can we actually regrow the thymus.

Mitochondria and Energy

Mitochondria these are the energy packs of your cells You may have learned that in your high school biology. And as we get older, the mitochondria get weaker. And the theory is, it's like a battery. If you can change electric drill and the battery wears out, keeps wearing, wearing out, and then it's like the energizer bunny. You replace the battery, it's back to brand new again.

So that comes in the theory. A lot of people who work in mitochondria say, well, all those people working on insulin resistance and things like that and heart disease. The heart disease is the number one killer. They're just band-aids. You can just fix your mitochondria, you fix everything. And the idea is, can you get your good mitochondria? We have a spectrum of good mitochondria and weaker mitochondria. Can you get your good mitochondria, regrow them, and then give them back to you and be completely rejuvenated? So I'm working with a company called Mitrix Bio that's trying to do that.

Brain Aging and Blood-Brain Barrier

Alzheimer's, dementia, brain, we all know about that as correlated to aging. and there's been quite a lot of controversy on the Alzheimer's research work in the last 30 years. Last year, we really found out that the plaques that people have in their brains may not be the complete cause of Alzheimer's despite 40 years of work and $40 billion of expenditure in R&D.

but there's a concept of a blood brain barrier there's a barrier that separates our brain from blood so when we get an infection we don't our brains don't get infected as we get older that barrier starts to leak and that seems to be correlated with aging so work with the company called Rezneuron on that.

Accelerating Research with AI and ML

Next thing is using machine learning and trying to say well okay how do we speed this up because I've only got 16 years left. I can't muck about with working on phones anymore. And how we're gonna speed this up? Well, one theory is use machine learning.

There's only one in 20 chance of getting a drug out when you're starting from the beginning. I want it to be more like seven in 20 right Can we get more chance And then it costs a billion dollars to get a drug out And it takes 20 years So can we use machine learning Trick one Trick two can we use all the databases that are now available? There's loads and loads of database, but they're not, they're all like splintered. Can we combine them?

And trick three, can we say, well, let's not invent any new drugs. Let's just repurpose the ones that are already there and use them in different combinations they probably cover the space already we don't have to invent a new one that's a school of thought and so a company I'm working on, Yasaman's over there you can talk to her she knows all about that.

If you put all these things together then you may have a case for an aging vaccine and that's really what we want to get to is an aging vaccine either Is it something you take once in your life or you take once a year? It could be a combination of these things. We don't know what it is.

Practical Lifestyle Interventions: Diet

But let's go back to basics. What can you do right now? No fancy drugs. Can you actually do it, get better with diets and exercise?

So diet, lots of things are implicated in aging. And some of these are obvious ones that you've seen and you've heard about. You may have heard of antioxidants, something called oxidative stress, which harms your mitochondria. These are free radicals associated with heart disease. And so we eat blueberries, strawberries, take vitamin C to reduce that.

Inflammation. this general increase of inflammation is when you get ill, when you cut yourself, the immune system kicks in. But as you age, the immune kicks in the system all the time. It's what's called inflammaging. And this seems to be associated. The key thing is associated. And it's very difficult to tease apart. Is it the turmeric you're eating actually affecting it? or is it something else in your good behavior?

Omega-3s, you've already heard about this. I think the data has come out that really, the actual pills themselves are not that helpful. Fish is.

Nitric oxide, if you're a runner, get increased recovery you can get that through beetroot juice and to help figure out if any of these things are working is coming up with a clock a clock natural aging clock to figure out if those methyl groups are actually changing as you take any of these interventions.

What else is there? Fibre. Fibre is good for you, that helps the ?microbiome, helps with many many aspects. This is work that's done at Stanford but it's not just any fibre. Different fibres help different people but one type of fibre, resistant starch, decreases cholesterol seems to have more effect than other types of fibre. Sort of wheat germ, it's in wheat germ, you can actually buy it as a supplement.

Timing of Meals and Exercise

It's not just what you eat, it's when you eat. Typically, a few hours before going to bed, take a walk after your meals, do any exercise of any kind, any time. It depends whether you have insulin resistance or not. If you're insulin sensitive, then afternoon's better. If you have insulin resistance in the mornings better. And it's really different for different people.

Ageotypes and Personalization

So we have this concept known as ageotypes, where at Stanford, we looked at 100 people and looked at different types of aging. So some of us are kidney agers, some of us are heart agers, some of us are immune agers. And you can actually sort of cluster people into these different groups. Some people are all four.

And the main thing is you might read an article, a friend might tell you, I did this, I did that. It might work for you, but equally it might not. So the trick is you kind of have to do your own things. Certainly measuring things is actually key to do things.

The health systems, the most health systems around the world, they don't measure things proactively. They don't give you tests. It's only after you get ill you.

So some of these things are more important than others because the trick is not taking one measurement once, it's taking it in different times and things measure more quickly.

Glucose Monitoring and Glucotypes

Finally let look at glucose monitoring because this has come up It used to be just type 2 diabetes people would get one of these Dexcom continuous glucose monitors that stick on you that measure glucose in your blood as you're eating. Now you can actually buy these things. I think Levels is a company that sold 500,000 of these monitors to people who are not diabetic.

And the reason these things are going out there is, again, to measuring what happens to you when you eat something. It turns out it's not just ageotypes, but also glucotypes. I spike on potatoes, but I'm perfectly fine on bananas and rice.

There's an Instagram website called Glucose Goddess. You say, okay, you want to eat chocolate cake? All right, fine, you want to eat chocolate cake. Here's how you do it. Take a 10 minute walk, have some broccoli, then eat your chocolate cake, and then have a 10 minute walk, and you'll find your spike will be much, much more reduced.

Sleep, Telomeres, and Social Factors

Finally, sleep. Sleep is very important. We had Bryan Johnson, who was the inventor of Venmo. He's a big supporter of sleep. Again, we see that skin gets better. Telomeres are the things at the ends of your chromosomes that get smaller as you get older. Getting good night's sleep is important.

And then thinking younger, being younger, being happy, being social. It turns out that if you're actually surrounded by young people, you're talking with young people, doing young things, playing with kids, that you seem to correlate to a longer life. but the thing is also remember cause and effect. So people who think they're old, maybe they don't attract many friends, right? If you're miserable, then people don't want to be with you. They don't want to be around you. If you're optimistic, the reverse is true. People want to be around happy people. And so therefore, you know, maybe people who are social live longer.

Backup Plans: Cryopreservation and Mind Uploading

Okay, what if none of this works, right? None of this works. Well, this is, we've thought sort of plan A is probably diet and exercise. Plan B is working with my friends Yasaman and Marco and we come up with a drug that will make us live a lot longer But then plan C we have to well it plan B it should be plan C indeed Plan C is cryopreservation, right?

Remember, I've only got 16 years left. How can I make that longer? Suppose we don't crack it. Can we actually get another 20 years? Cryopreservation means freezing you. And there's a couple of companies, actually it's amazing, not many people have been frozen. I think a couple of companies have been out there. There's only about 3,000 people that have been frozen up in about 40 years. And it's a different price if it's just your head versus the whole body. And actually you might want just the head because the body just crystallizes. And so one of the problems is, can you do get crystals in your body? So if you freeze the entire body, you have more chance of crystallization.

And the theory there is, well, has anyone been ever unfrozen and brought to life? And the answer is no. But the proponents say that doesn't mean it can't happen. Lots of things that happened today, people thought were impossible. And it's a bit like if you're in an airplane, someone said, here's a parachute. We're not sure if it works, but we're about to crash. Do you want to take it or not?

Second idea is sort of like singularity, sometimes people call it. Well, we just upload our brain, our memories, our connections into a machine. So the problem with that theory, okay, suppose you even did it perfectly, and you've got a replica of me over there. Is that me? I want me to be me, right? Will that actually be me again? You want your feelings. This theory of embodied consciousness. Actually, no one really knows what consciousness is, really. I think it's a thousand definitely. The philosophers have probably done more work on it versus us computer scientists.

But you have to be connected to something. You have to feel something. And in computer science, okay, we've figured out how to type letters now and write books. But can we figure out how to program guilt or envy? and at Stanford we've got this project called the Boundaries of Humanity Project that if we start to change people, change things, can you actually be at what point do you stop being human And so those are the things that we will talk about in the next 30 years.

Closing and Invitation to Q&A

If you want to find more papers, we've got lots of papers on the Stanford website. About 100 papers or so written by students on different topics. as the bladder age, not just biological concepts, but also financial concepts, social concepts.

So I'll stop there and just open up for a few questions. And I'm not sure we're getting questions on YouTube, but thank you very much. And just let's start for a few minutes for questions. Clive, is that right?

Q&A Session

Thank you very much, Ranjan. If you have a question, Teresa with the microphone will come around. So if you raise your hand if there's any questions. We have about maybe 15 minutes of questions.

Q: Predictiveness of Death (Unnamed Audience Member):
My question is, in terms of predictiveness, can you predict when someone will die? therefore the extension of life off the back of that.

A:
Right, so the question is, can we predict when someone will die? So instead of saying, slightly different nuance I think I'm getting from there, you're saying, instead of predicting the age of death, you're saying, well, how many years have you got to live? Which is not quite the same. Because there could be a theoretical lifespan, healthspan for you, but you may be doing things that don't achieve that today.

So some of the things, doing no exercise, no diet, BMI, certainly certain diseases, you catch a certain cancer. People have got many, many statistics on if you've got pancreatic cancer, you've got a year left. If you've got this kind of cancer, so much time left. I think the main thing is we know the averages. And the problem is, can we get prediction for you? And I think that's still a science, even though people are working on these aging clock, personalized aging clock.

Right now is about 60 clocks out there and if you're going to take one clock I would take the number of companies and labs take measurements on lots of those clocks and that will give you maybe a closer answer there's not an exact science this.

Q: Healthspan vs. Lifespan:
You've talked about age. You haven't talked about healthy age. And I mean, to me, surely it's not how long you live, but how long you live as a fit, healthy human being. my second part is so if you've got a predisposition to Alzheimer's at 80 do you want to live to be 120 does that would give you 40 years with Alzheimer's.

A:
No completely I think I did actually mention it very very briefly very briefly quickly and I do have one slide that we flick flow quite quickly but I didn't mention it right at the beginning there's no point living in the last 20 years in misery there's two concepts that the vocabulary definitions usually Lifespan is what number of days you could live but where is the other concept is health span is exactly what you're saying the number of years of healthy.

Lifespan most of us I'm sure have Relatives or people who have lived in misery for a number of years And we don't want that the ideal scenario and maybe the idea so I think even in Britain this guy used to show up on TV he was Jack LaLanne and he was a sort of Mr. Universe, he'd do exercise, vegetarian, anything you should possibly do good behavior, he did. He was doing push-ups right to the end but what got him was pneumonia but he was doing push up to one week before. His end of misery time was only like one week. I think most of us would go with that and so you're quite right. So those concepts are out there in the thinking. We want to get health span, not life span, definitely.

Q: Genetics, AI, and Disease Prediction (Unnamed Audience Member):
Although genetics only plays 20 role in say cardiovascular disease We know that there are interactions with genetics and certain other factors Do you think AI will be able to give a better prediction of, say, cardiovascular, it could be other diseases, in the future that would give us a better sort of individual risk?

A:
Yeah, thank you for that clarification. We know that genetics is 16%, but certain genes, like the Huntington's Genes disease or even the ApoE4, Alzheimer's, ApoE4 is about 40% chance you'll get it. Huntington's is about 90% chance you'll get the disease. Certain genes are very deterministic, so it's not 16% for those genes.

And I do think, going to the second part, because the more data we have, and as we know, it used to be people looked for that one gene that causes cardiovascular disease. Most diseases, most common diseases, is a long tail of genes, not one gene, and genes affecting other genes. And hitherto, we haven't really had the computing power, number one, and number two, we haven't had the data to do it.

That's all changing. We're wearing all these things, billions of samples. We're not actually getting, not that many people being sequenced. Only about 40 million people have been sequenced in the world. if you play it forward it gets cheaper and it's like standard of care you just get you're just sequenced can we get to a billion people when you get to those levels then we can get AI going to get to work.

Q: Chronobiology (Daniel):
Go ahead Daniel so Ranjan thank you so much for the very inspiring talk I'm glad you mentioned I think you're not what you eat but when you eat and of course that was all introduced by professor Franz Halberg from Mayo Clinic and the area is called chronobiology yeah so would you be able to elaborate a little bit more on the role of chronobiology and maybe slowing down the aging.

A:
Yeah I think it goes back to measurement one of the things is I used to be quite critical of these wearables because I just put it in a drawer after three months and forget about it. But now, as you start to use it, you can get nudges. And this is why some of these continuous glucose monitor sensors where people are using it people are curious They want to know if you can reduce the spiking and you get these popular websites saying okay you want to eat pizza this is how you do it right the education the data.

Before before we had these continuous glucose monitors we didn't actually have any of that data except in the research labs like you say the medical clinics Stanford would measure people but there's only a relatively few number of people if we can do it on large numbers then we're going to get much more data so even though it's an average we're going to get clusters okay so we want it for you not the average but you might be like to be similar to you over there and we can put you in the same bucket because you get the same lifestyle the same age the same some some maybe commonality in genetic profile because We're still 99% the same and 98% the same as a monkey.

So I think, again, we're going to need more personal data to get personal information.

Q: Moral and Societal Implications (Unnamed Audience Member):
What about the moral question? We have 8 billion people on the planet. We know what they're doing to the planet. We've got an aging population, more and more elderly people being paid for by the taxes of our children and grandchildren in employment. How do you answer that?

A:
Yes. And that goes to the AI scenario thing as well, because, you know, things are going to be very much more productive. Will there be enough jobs? My thinking is anything that can happen will happen. You can't stop it. You know, people will start inventing things, keep inventing things, either in the biology area.

If you can live longer, we've got a whole complex, industrial complex, trying to come up with drugs. If we can change the dynamics a little bit, because right now we are encouraging drug companies to come up with new drugs and also charge a lot every year. So you're on it for the rest of your life. Can we change it to the opposite where you just use things that are already there? It's free. and you get there.

And the next question is, it's gonna happen, we saw those charts at the beginning. There'll be a lot more older people. In Japan, it's already there. There physically aren enough young people to look after the old people What are they doing They building robotics building other systems The older people just handing over their businesses to young people because no one actually wants to own a farm. So they're just like, you can have my farm for free.

So we're seeing Japan in particular, they have no immigration, so it accentuates the problem. So you'll have some of these other dynamics where it's almost self-imposed, right? where you don't have enough young people to solve it quite easily with immigration. But if you decide not to do it, then you've got to work on these other principles.

I'm an optimist at heart. I think there are solutions, vertical farming, which can support us in other areas. Historically, when we've had these doomsday scenarios, the Club of Rome in the 1960s said, we'd have an apocalypse in 1980 or so. because we'll run out of oil, we'll run out of food, and it didn't take account of the advances of technology to make us more efficient. So I think I have a more optimistic approach. But it's not without work.

Q: Supplements (Henry Feta Yunbo, Live Stream):
Hello. Well, we have a couple of questions coming in on the live stream. So the first one's from Henry Feta Yunbo. Ranjan, what weight would you put on supplemental pills?

A:
Yeah, so I think, I think I wouldn't put zero. Some people say just they're all waste of time, don't bother. I think Lord Winston said that basically. He said everything's a waste of time except vitamin D. I would not say it'd be as pessimistic as that, but I think it's again different for different people. And again, you have to sort of tease apart.

And why it's different for different people is that different people have different deficiencies. But there's also a U-curve thing. More is not necessarily better. Less is not necessarily better. If it's not working, you may not be taking a strong enough dose. If it's not working, your dose may be too strong. So it's very difficult to know what to take.

For myself, somebody might ask this question, well, Ranjan, what do you do? I've tried lots of things, lots of hacks. NMN makes no difference to me, NAD Plus makes no difference to me. These are these popular supplements. Vitamin D I feel no difference to me. maybe I need to take it for 10 years, 20 years, before I notice any difference.

The only thing that has made immediate impact is when I went on a diet with no sugar and a vegan diet in combination. Cholesterol went from 165 to 130 in about three weeks. and did almost the same thing, but with a Mediterranean diet, but no sugar, almost as good. So I think sugar is bad. Sugar is definitely bad. That seems to be, and we see this in the glucose monitoring stuff, but I still like chocolate cake. I still like ice cream. And for mental health purposes, I think the question over there, we want to be in misery for the next 30 years. I think I can justify the occasional slice of chocolate cake and ice cream for that purpose.

Q: Epigenetic Clocks (James Gatterby, Live Stream):
Thank you And if we could just do one more from the live stream James Gatterby says there are so many epigenetic clocks which if any are actually useful.

A:
I think you can say that I think we at the early stage For those of you who don't know what these clocks are, it turns out with a spit sample or blood sample, you can measure your biological age. And the original one was by Steve Horvath. It was a commercial item. about $500. My prediction in the next year, 18 months, these clocks will drop in price to about $100.

I think you'd really need to take three or four of these different clocks to actually get the average. One won't be sufficient. And I've given you some of my measures of not buying a clock at all. You just measure your running time and your maximum heart rate. I did a telomere one and told me I was 20. That's nice to create some of my running one. I'll stick with that one. You stick with the one that's the best, right?

Best for you. But I did the skin recognition one, the face recognition you can go to the NVIDIA Olay website there a face recognition and it told me I was 58 So again I still look old That the problem So yes try to answer that question.

Q: Lifestyle vs. Biotech Contributions (Unnamed Audience Member):
Hi, Ranjan. Thanks for the talk. So looking out, I don't know, 30, 40 years with people living out to 120, how much of that do you think will be from, like, better lifestyle, just people exercising more, eating better, knowing, like, their individual strengths and weaknesses versus like what biotech and pharma is researching and things that we'll take externally to.

A:
Yeah, I think it's about 100 or so. It seems like if we just behave ourselves and we're getting more education, marathons, 1970, you know, 1,000 people have entered the Boston Marathon and women are not allowed, too dangerous for women. Now 30,000 people every year does about half of them women at the Boston Marathon.

We haven't had that scene, what that large number of sort of amateur athletes, not such as marathons by itself, is going to have in decades to come But it seems like if you look at Japan where they pretty healthy you know the average age of death is 83 84 a bit higher than the UK and the US We're going to have to need a little bit more of a fillip, and we may be able to get to 90 or 100 with addressing some of these big diseases like Alzheimer's. But getting to the 120, I think we'll need some biological intervention. I think I'm pretty optimistic we'll get one.

Core Intuitions, Mechanistic Insights, Tricks, and Main Concepts

• Longevity Escape Velocity: Core intuition that radical lifespan extension doesn't require immortality upfront; successive ~20-year tech leaps (e.g., drugs, AI-derived therapies) can perpetually outrun aging if innovations arrive faster than personal mortality.
• Healthspan > Lifespan: Mechanistic pivot from mere survival to functional years; target key organs (brain, heart, liver) to avoid frailty; exemplified by Jack LaLanne's minimal morbidity window.
• Chronological vs. Biological Age: Biological age via performance proxies (VO2 max, max HR = 220 - observed, grip strength, one-leg eyes-closed balance) decouples from calendar age; AI clocks (e.g., aging.ai, Horvath methylation) integrate blood/spit biomarkers for ~decade-scale predictions.
• Genetics ~20-30% vs. Lifestyle Dominance: Insightful confounder separation—lifestyle transfers intergenerationally mimic heritability; polygenic long-tail risks (e.g., ApoE4 40% Alzheimer's odds, Huntington's near-deterministic) yield to epigenetics.
• Causation-Correlation Skepticism: Ubiquitous trick—trials benchmark against unhealthy averages; U-curves plague dosing (supplements, metformin blunts exercise gains/inflames, rapamycin boosts insulin resistance); measure personal clocks pre/post to validate.
• Hallmarks and Unified Theories: Damage accumulation (sarcopenia, stem exhaustion, genomic instability) vs. systemic fixes (senolytics clear senescent cells, parabiosis/heterochronic plasma shares youth factors bilaterally).
• Autophagy via Intermittent Fasting: >15h fast triggers selective cannibalism (senescent/precancerous cells first); skips breakfast compresses feeding window without calorie cut.
• Exercise Molecular Mimicry: Beyond mechanics, myokines signal stem cells/epigenetics; Stanford seeks pills replicating (e.g., post-marathon repair cascades).
• Personalization via -Types: Ageotypes (Stanford: kidney/heart/immune/liver-dominant clocks); glucotypes (CGM spikes vary individually—potatoes spike speaker, not rice/banana); hacks like pre/post-walk + veggies blunt glucose excursions.
• Biotech Frontiers: Epigenetic reprogramming (Yamanaka factors reverse 4 hallmarks/cell age); thymus involution reversal (T-cell neogenesis); mitochondrial allotransplant (autologous good mito expansion); blood-brain barrier sealing (leakage → neuroinflammation > amyloid plaques).
• AI Acceleration: Repurpose existing drugs/combos (cover chemspace sans novelty risk); federate splintered databases; ML lifts hit rate 1/20 → 7/20, slashes $1B/20yr timelines.
• Aging Vaccine Vision: Single/multimodal jab (annual?) targeting hallmarks; robotic/AI aides for societal scaling (Japan precedent).

Transcription Difficulties and Uncertainties

• Supercentenarians: "jean colmec" → Jeanne Calment (verified 122y record); "Maria Moreira" → Maria Branyas Morera (117y, San Francisco-born); "your belinda california" → Loma Linda California (blue zone).
• Companies/labs: "Rubida" → Rejuvenate Bio (epigenetic reprogramming, Marco likely exec); "reservoir neuro" → likely Rezneuron or Revita Neuro (blood-brain barrier, uncertain—possibly "Reviva" or audio error for "Cerebrovascular"); "Jemmika" → uncertain, possibly "Chemika" or "Gemini" (drug repurposing, Yasaman mentioned); "Mitrix Bio" → Mitrix Bio (mitochondrial firm).
• Fibers/supplements: "rinoxolone" → best guess "resistant starch" (cholesterol-lowering, wheat germ-associated; alternatives: inulin, beta-glucan—context favors resistant starch).
• Biology terms: "teno-meas" → telomeres; "inflammaging" inferred from "inflammation" context; "Apo4E" → ApoE4.
• Minor: "currents" → "Silicon Valley" TV show; "Bladder age" → likely "broader age" or "various aging" (Stanford papers context); "parabiosis" clear but heterochronic plasma implied.
• Q&A names: "Franz Halberg" → Franz Halberg (chronobiology); "Henry Feta Yunbo" → possibly "Henry Fetayu Nbo" (live stream garble); "James Gatterby" → James Gatenby.