3 Takeaways - Dr. David Agus on The Hopeful Science of a Longer, Healthier Life (#280)

Episode Date: December 16, 2025

Dr. David Agus, USC Professor of Medicine and CEO of the Ellison Institute for Transformative Medicine, treats presidents, CEOs and cultural icons and has spent decades studying one question: What determines how long and well we live?His answer is hopeful: Only 4% is genetic. The other 96% is under your control.In this episode, he reveals why elephants rarely get cancer, why giraffes never get heart disease, and what inflammation does to nearly every organ in your body. He also shares the simple, proven habits that matter more than DNA, and destroys the myths quietly harming millions.Science-backed. Actionable. Hopeful.

We all want to live longer and better. But what if longevity isn't mostly genetic, as we often think? What if 96% of how long we live is actually within our control? Hi, everyone. I'm Lynn Toman, and this is three takeaways. On three takeaways, I talk with some of the world's best thinkers, business leaders, writers, writers, politicians. newsmakers and scientists. Each episode ends with three key takeaways to help us understand the world and maybe even ourselves a little better. Today I'm excited to be with Dr. David Agus. David has treated presidents and popes. He founded USC's Transformative Medicine Institute. He's written multiple

wonderful New York Times bestsellers. But what really sets him apart is this. He doesn't just treat sick people. He's trying to keep people from getting sick in the first place. Think about it. We spend trillions on health care, but most of it is sick care, waiting until something goes wrong than trying to fix it. David is leading a different movement using data, lifestyle and science to help people stay healthy longer. His patients have included President Bill Clinton and Pope John Paul II. His books, The Book of Animal Secrets, The End of Illness and the lucky years have changed how millions of people think about their health. His insights are both hopeful and actionable. Welcome, David, and thanks so much for joining three takeaways.

today. Well, my privilege. It is my pleasure. Google bought the Ancestry.com database and found that only about 4% of longevity is genetic, meaning that 96% is more or less in our control. What does that really mean for how we live? Listen, to me, that is the greatest hopeful statement in the world, which is your health outcome is under your own control. And it's not destined by who your parents were. You know, it's very interesting from that same study, and this is the coolest statistic ever, is that I can know better how longer you will live

if I look at how long your spouse's mother lives versus sequencing your genome. You know, your behaviors are classically similarly to your parents and people marry people of similar backgrounds. Smokers, marry smokers, couch potatoes, married couch potatoes. But what we know is there's certain simple habits that can have a dramatic effect on how long we will live. What our weight is, do we smoke, what our exercise pattern is, what we eat.

Those are important and under our control. So I love the fact that it's not predestined, does not predetermined that we're in charge. Roughly 60% of health care dollars are spent in the last two years of life. What does that tell us about our approach to aging? You know, it's very interesting. There's that statistic that comes out over and over again, which is we're not good at knowing the outcome in medicine or we're not good at telling people the outcome. We put tremendous resources at the end and we put very little to teenagers, to 20-year-olds

to 30-year-olds. And the argument has always been if you start to ship those resources early, we can have better long-term outcomes. And that's what we care about, right? when you intervene on diet and lifestyle exercise or lipid levels, statins, and other things early, it's better than intervening later. It's a lot cheaper to prevent disease than it is to treat disease. And at the same time, it's a lot better for the patient to not have a disease through prevention

rather than getting the disease. And then we also, and this is the beauty of where AI is now, is that we're also getting so much better about knowing what the outcome will be. And so if I know the outcome is going to be negative, I can let somebody do something, which the last year you can do in the United States was 1956, which is die with the diagnosis being old age on a death certificate rather than having a cause of death. Like people die with dignity rather than put them in the ICU, which tremendous resources costs and at the same time isn't good for the individual.

So I do think we need a reckoning, a call to arms, and to use all of the data we have now in AI to get better. outcomes interpretation and learn how to communicate that to the patient. Before I ask you more about data and AI, you've cared for leaders like the Pope and Bill Clinton. What habits have you noticed in people who stay purposeful and energetic into later life? People who are purposeful and energetic do better. There's remarkable data in one of the largest studies ever done in Europe that every year you delay retirement, you're reduce the incidence of Alzheimer's by over 3%. So you don't use it, you lose it. It doesn't

have to be your primary job. It could be something else, but you want to be uncomfortable and you want to keep your brain engaged. And I think people who do that do better. We don't necessarily know why, but that works. People with lots of social connections do better. We are social creatures and we're made to do so. And the social connections change our hormone, change how we feel. So if you look at a dog in the eye, your love hormone oxytocin goes up. And so it is there. Your blood pressure lowers. Your whole physiology changes with that hormone.

And we feel it. And so the people who do that do better. And so what we need to do is kind of learn from those behaviors and those habits. You know, I do think with AI now, each of us is going to be, if we can survive the next three, four years, we will probably live a decade longer. And so we need to change everything we do in that. regard. Do we really need to retire at age 65? If we've got 30 more years of functional good life ahead of us, maybe we should figure out ways to engage our elderly more, to use them more and their wisdom more to help younger people and mentor them and other things. I think we need a

reckoning now. We're not dying in young ages anymore. We can live a long time and live healthy years. How do we use that for good? Every seven years, our cells renew themselves, but errors accumulate over time. How does that process drive aging, cancer, and other diseases? I think that's the billion-dollar question. There was a remarkable experiment done by Wanda Ruth Lunsford in the 1950s. And what she did was she took an old rat and a young rat and she tied their skin together after anesthetizing them. And after two or three days, their blood supplies joined. And what she saw several weeks later is the old rat, the gray hair turned brown again, the most of the most of the neurons were growing in the brain, the muscles were bigger. She claimed she reversed aging.

And they actually pushed her out of science. It was the last paper she ever published. Well, several years ago, a group at Harvard, a group of UCSF and Stanford separately repeated Wanda's experiment and it worked. It turns out our stem cells at age 25, they turn off. And now we've identified the factors in kin to what the Chinese group that can turn them back on. And once you turn them back on, you could regenerate things. Our body is good at surveilling. for damaged cells. So while DNA changes accumulate, you've got three billion letters in that code. So a change here and there is going to happen every time the cell replicates or divides, but we can now find them and kill those cells. And when you look at some crazy things,

like people taking high-dose antioxidants, what you see in most of those studies, vitamins, is increases in cancer. Why? Because our body uses free radicals to get rid of the bad damaged cell. You block them with high-dose antioxidants, which we're we're not made to have, those cells can survive and become cancers. It's as simple as that in many regards. I'm probably oversimplifying things, but the key is to go to do things where there's data. And to me, that's going to be the key. Our immune surveillance system is good.

We're developing tools now to even make it better and get rid of those bad damaged cells. And so that's what's exciting. As you get older, immune surveillance goes down, right? We know that. Elderly die of pneumonia, whereas young people can get over infection very easy. But if we can make those immune cells young again, that's not going to happen. And they're also going to surveil against damaged cells and get rid of them. Before I ask you for the do's and don'ts, I very much enjoyed your book of animal secrets

in which you talk about some remarkable characteristics of different animals. I was surprised, astonished to learn that elephants rarely get cancer, and elephant females can give birth into their 60s. And as for giraffes, they never have cardiovascular issues like heart attacks. What can we learn from elephants, giraffes, and other animals? It's pretty cool, right? We've all been in the earth a million years, all of these different species, and we've all evolved under the same conditions.

And some of the traits animals have acquired, we can learn from and actually try to recapitulate or, you know, do the same thing. Elephants, you know, I was on my family, you know, Sabari, and Africa. It's the coolest trip we ever took. And I'm with the guide, and I go to the guide who's, you know, these wise person who have done this for years. And I say, listen, those elephants are 40, 50 times bigger than us. They're 40, 50 times more cells. As you said before, is every time I cell divides, it can get a mutation or a change in DNA.

So with 40, 50 times more cells, much more probability of getting a mutation that leads to cancer. So there must be lots of cancer in these elephants. He looked at me like I was crazy. He goes, no, elephants rarely. get cancer. And I said, what? How can that be? A group in Arizona, amazing group, sequenced elephants, and they show that we have a gene called P53. Its nickname is the guardian of the genome. It looks for errors and then kills those cells. You and I have one copy of this gene. Well, every elephant on every continent has 20 copies of this gene. If this gene changes or gets mutated, it doesn't work.

They have 20 copies, so they have this redundancy there so they don't get cancer. And part of it is that evolution thing you refer to, right? Is they get birth until their sixth decade? Well, if that happens, you can't die earlier. You're not going to have enough children. The dominant male protects the herd until the day he dies, so they have to stay healthy until elderly age, and they figure out a way to do it. So how do we get rid of that inflammation-mediated DNA changes?

Well, the lesson there is just block inflammation today. We can't add more paper 3-D yet. Maybe one day we will be able to, but now it's block inflammation, the source of these DNA changes, and we can do that. Things as simple as taking a baby aspirin today or lowering your LDL that bad cholesterol are ways to do it. Behaviors, non-traumatic things are ways to do it. And so there's a lot to learn there. Those giraffes, they have a blood pressure of 300 over 200. Our max blood pressure is, you know, kind of 150 over 70.

I say you have a high blood pressure. Yet they don't get heart disease. What can we learn from that? And it's wild how they've adapted ways to basically protect their blood vessels. And it's pretty amazing, right? That giraffe head is way up here. If you bring that head down, they actually pass out. So they need that blood pressure to get up there.

Our spacesuits are actually made to mimic a giraffe skin. So they make these very tight skin so blood doesn't get out of their blood vessels, which it would do in us if our blood pressure goes up so they can tolerate that. And at the same time, by having that, they can push blood to the brain. Well, you and I don't have that. So if you've ever hurt your shoulder or your arm, you have to sleep sitting up. That doesn't work very well. You actually, when you're not at face of gravity, so your heart and your brain aren't at the same level, you don't get good deep sleep.

Giraffes get around that with that tight skin. We can't. More deep sleep you get, the more your brain is going to function better the next day. Long term, the better your health outcomes, as simple as that. You helped develop a breast cancer drug that took over a decade with AI and genetic databases. How different could that process look today? Making a drug, literally took a 10-year period just to make the drug, and then seven years to test it. Now I can say, hey, with AI, here's a protein.

I want something that binds right here. Here's every other protein in the body. I don't want it to bind to those. here are the genes for metabolism. I wanted to last this long in the blood. And here are the genes for the immune system. I don't want it to be recognized as farmed by the immune system. And with those constraints, I can make a drug literally in weeks.

In the last six months, we've made five drugs. And so the probability of working is actually greater, because I know it won't bind to any other protein in the body, than a classic drug. And that at the same time, I know this is going to sound a little weird, is we're taking human organs that were ineligible for transom, transplant, things like a liver. And we can keep them alive for a while with a new thing that pumps blood and plasma through them and test drugs against human organs instead of mice.

So all of these things with AI are enabling us to develop drugs quicker and better. And in clinical trials, instead of saying, hey, half of you're going to get the drug, this exciting drug, because you have a deadly disease, and half we're going to get a placebo because we have to see if the drug makes you live longer, questionable ethics right there, but that's what we do. We can say, hey, listen, we're going to give you 100 people this drug, and we're going to find 100 people from the database who are exactly the same in terms of their health parameters, see their outcomes, so compare to a virtual. So basically, you have a digital twin we're comparing you to instead of giving somebody a placebo. It means the trials are half as expensive, half the size.

You don't have to give people a placebo, and take half the time to get done. So this is a game, changing time we're dealing with now. We're going to have new drugs. And I get to see what's in the pipeline and the amount of new drug to treat diseases is really staggering and so exciting. So exciting. You've said that inflammation is one of the root causes of aging and disease. Can you explain why? First of all, it wasn't me that said that. It was the data that said that. And so the data really show is that inflammation is the body's response. You can imagine, right, if you have a little cut on your arm and it turns red, that's inflammation. Well, imagine that throughout all of the blood vessels in your body.

That response, basically, to get rid of something, which is what inflammation is, that leads to the buildup of cells, which leads the heart, for example, to the buildup of cholesterol. That can lead to the heart attacks. In the brain, it can lead to neuronal death or atrophy of the brain. And organ by organ, we can start to see troubles there. So you block information temperate down and actually live longer and better. How can we tell if we have inflammation and what can we do to keep it in check? There's a poor man's metric.

And I say poor man's metric because it's a generalized marker of inflammation called high sensitivity C-reactive protein. So it's what we have today. I think in the near term we're going to get inflammation markers for every organ. So right now we have these metrics, inflammation C-reactive protein. And then there's the coolest test in medicine. It's called the erythrocyte sedimentation rate, ESR. It's one of the oldest tests we have.

And get a load of this, because it's so old school, it's awesome. You take a drop of blood of somebody, and you drop it into a sugar solution, a thick sugar solution. And you count how long it takes the cells to reach the bottom. The longer it takes, the more inflammation in the body, and that certain proteins are upregulated to make the cells sticky. And we measure this test in millimeters per hour. So it's the speed, basically, that the red cells drop. It's the coolest thing in the world, the ESR.

So those two tests are metrics now. But I think the best marker of inflammation is also how you feel. If everything is aching and all, you've got inflammation. That's not good also. So you put them all together. We've got a pretty good estimate what's going on in your body. And there are things like there was something called the Jupiter study. So they took people with normal cholesterol, who had elevated inflammation, and they put them on a statin, a pill called Crestor.

And what they showed is they were able to dramatically delay heart disease and reduce cancer in those people by just going on a statin. So simple as simple as that, statins are inexpensive, a 90-day supply without health insurance at Walmart costs $10. So they're relatively inexpensive. And in most people, they have no side effects. In a very small percentage, you get muscle lakes. If you have it, you stop and it's gone the next day. So certainly something with potentially tremendous upside and very little if any downside

or something that we should be doing more of. You've found that several things are surprisingly toxic for us. Toast, for example, as well as vegetable and fruit juices and smoothies. Can you explain? most people think all of those are healthy. Let me take them one by one. When you put bread in a toaster, it turns brown. That's the sugars joining together forming something called acrylamide,

which in an assay has a carcinogenic potential. Do I think it's a problem? No. So I'm all four toast. Roasting coffee beans does the same thing. I'm not sure these assays are reflective of what's happening in us. And if the risk is there, it's so minimal. You shouldn't change your behavior.

If you like toast, eat toast. fruit juices and smoothies on the other extreme. Once you squeeze something out of a fruit, all of the nutrients to grades very quickly when exposed to oxygen and light, and you're basically just drinking sugar. And the same thing with putting something in a smoothie or a bledger. Don't do the things that are convenience or make other people money. Do the things that are simple. Eat fruit, eat vegetables, eat your food, don't drink it.

What are some other surprising foods in addition to, toast and fruit and vegetable juices that are bad for you? We know because of basically what we as humans do, some foods have some toxins in them. Swordfish, remember over 100 servings of salmon is equivalent to one serving of sorefish on a mercury basis. Why do the fish get mercury? It's an impurity in coal. When you burn coal, it goes to the atmosphere, it rains, it goes into the waterways,

and then deep down, certain bacteria converted to methylmercury, which causes. is a problem. And the same is true with certain plants. Kale, for example, absorbs a lot of heavy metal from the soil. So you don't want too much kale in your diet. You especially don't want a kale smoothie where you make it very bioavailable or easy to absorb. The bottom line is you don't want too much of anything in your diet. And certain foods like the swordfish, you probably want to avoid. Fish are amazing, wild fish, those cold water fish are great for our brain in our body. But don't do it in a pill. Don't do the fish oil capsules. Do the fish. One four-ounce serving a salmon is equivalent to 11 fish oil capsules. You have a beautiful fish. You sell it to

the seafood. So if you're a fisherman. If you have an ugly looking fish, you know, that's not doing well, you sell to the fish oil company. Which would you rather eat? What are the three simplest daily habits that anyone can start today to reduce inflammation and extend their life? One of them is probably the simplest and most obvious. It's that as movement over time, right? Our bodies were designed to move. So the more you move, the better you will do. Your lymphatics that control your immune system have no muscle in their wall.

It's the rhythmic contraction of the muscles in your legs when you walk that actually make your body work. So just figure out a way to get more movement in your day. It doesn't have to be running a mile at a fast pace. It doesn't have to be getting sweaty or your heart rate up. Just moving works. You know, every hour get up and walk around. Look at any, you know, sneaky sources. If your feet hurt the end of the day, you're probably wearing the wrong shoes.

And that's inflammation. And so you want to look at those sources of inflammation. Even if they're not the most attractive shoes, we're the ones that are the most comfortable. And then, you know, the last one is going to be downtime or rest. You need deep sleep at night to make your body. recover from what happened during the day. For me, the earlier I eat dinner, the more deep sleep I get. So I try to eat early.

What are the three takeaways that you would like to leave the audience with today? Number one is that it is a time of hope and optimism. I look at my field and what's happening and it's so positive. And I think science and technology are going to solve a lot of the problems that we have today. It's not going to be politics. It's not going to be policy. It's going to be science. technology. Part of my job is to translate that science, that technology, that optimism to

people. Number two is we have the tools now to prevent most disease and they're accessible to everybody. Everything that you can do to prevent disease and live well is accessible to every person in this country for minimal, minimal dollars. This is not something that requires an expensive technology or an expensive pill. This is something that is accessible. to everybody. And then the third really is, is that you are in charge of your own health. You go to your doctor once a year. I want you to look at your body for changes to tell him or her what's going on.

I want you to check your blood pressure at home in the morning, at night, when you're getting up, when you go to bed, when you're relaxed, when you're pissed off after a phone call. With enough data error goes away, don't just do with the once in your doctor's office. You are in charge of your own health. Your doctor is not. David, thank you. Thank you for your time today. And thank you for all of your work to help people live longer, healthier, and better lives. Thank you, Lynn. It was a privilege. I'll talk to you soon. If you're enjoying the podcast, and I really hope you are, please review us on Apple Podcasts or Spotify or wherever you get your podcasts.

It really helps get the word out. If you're interested, you can also sign up for the Three Takeaways newsletter at Three Takeaway. com, where you can also listen to previous episodes. You can also follow us on LinkedIn, X, Instagram, and Facebook. I'm Lynn Toman, and this is three takeaways. Thanks for listening.