WEBVTT - Can We Slow Down Aging? 0:00:15.356 --> 0:00:33.516 Pushkin. I'm Jacob Goldstein, and this is what's your problem. 0:00:33.716 --> 0:00:37.276 My guest today is Near Barzilai. Near is a physician 0:00:37.356 --> 0:00:40.876 and a researcher, and he runs the Institute for Gero 0:00:41.076 --> 0:00:44.676 Science at the Albert Einstein College of Medicine in New York. 0:00:45.276 --> 0:00:49.276 Near's problem is this, how can lifestyle changes and drugs 0:00:49.636 --> 0:00:53.476 slow the process of aging. In our conversation, Nier and 0:00:53.516 --> 0:00:57.196 I talk about the search for biological markers of aging, 0:00:57.836 --> 0:01:02.156 existing drugs that might reduce the risk of diseases associated 0:01:02.156 --> 0:01:05.276 with aging, and what he learned by studying the genes 0:01:05.316 --> 0:01:09.396 of people who lived to age one hundred and beyond. Also, 0:01:09.756 --> 0:01:12.196 we talk about the meaning and origin of the term 0:01:12.476 --> 0:01:16.076 gyo science. To start, I asked her how he decided 0:01:16.116 --> 0:01:18.076 to study the biology of aging. 0:01:18.756 --> 0:01:22.676 It actually happened young. It happened with my grandfather that 0:01:22.996 --> 0:01:27.196 walked with me every Saturday telling me about his life 0:01:27.436 --> 0:01:30.796 as a young person. And he was sixty eight. It's 0:01:30.836 --> 0:01:36.636 the year he died. He was looking old, fat, slow, 0:01:37.716 --> 0:01:43.276 and for me it always it almost became immediately clear 0:01:44.116 --> 0:01:47.996 that that's where I'm going, Okay, So it became the 0:01:48.076 --> 0:01:53.516 biggest question in biology of aging. When I went to 0:01:53.996 --> 0:01:58.956 my residency. I had an attending and whenever I presented 0:01:58.956 --> 0:02:02.876 the patient, he would stop me. I would say, this 0:02:02.956 --> 0:02:05.116 is a seventy five year old woman, and he would 0:02:05.116 --> 0:02:10.196 stop and say, but does she look younger than their age? 0:02:11.116 --> 0:02:14.236 And after a while you saw that it mattered. You 0:02:14.276 --> 0:02:16.756 can have a ninety year old guy and it comes 0:02:16.756 --> 0:02:18.756 to the emergency room and he has some infection and 0:02:18.796 --> 0:02:21.596 with some antibiotics, he'll be fine, and a seventy five 0:02:21.676 --> 0:02:24.396 year old woman that all her systems are totally gone, 0:02:24.676 --> 0:02:28.236 and you know, you know where she's going, and that 0:02:28.276 --> 0:02:33.876 it's important in decision making. I want to say that 0:02:35.276 --> 0:02:39.836 this is thing that I think people intuitively understand that 0:02:39.876 --> 0:02:43.516 there's a biological age. I think it's more important to 0:02:43.636 --> 0:02:50.196 know that aging, this biology is what drives diseases. It's 0:02:50.236 --> 0:02:53.156 not that we get heart attacks and we become old. 0:02:53.276 --> 0:02:57.236 It's the opposite. We become old and that drives diseases. 0:02:57.836 --> 0:03:01.156 I mean, intuitively, we also know that, right you're much 0:03:01.196 --> 0:03:03.276 more likely to get a heart attack at seventy five 0:03:03.316 --> 0:03:04.196 than at twenty five. 0:03:05.236 --> 0:03:08.196 That's true, but let me give an example that you'll 0:03:08.236 --> 0:03:13.956 explain it better. You can be born with genes for Alzheimer's. Okay, 0:03:13.956 --> 0:03:17.076 there's a gene called apo E four. If you have 0:03:17.116 --> 0:03:21.076 two copies of these genes, you are really high risk 0:03:21.156 --> 0:03:24.836 of getting alzheimer at sixty or seventy and you'll be 0:03:24.916 --> 0:03:28.156 dead by the time you're eighteen. But when you're born, 0:03:28.716 --> 0:03:31.876 you're not demented. And when you're one year or ten 0:03:31.956 --> 0:03:34.756 year of fifty year, you're not demented. You meet the 0:03:34.796 --> 0:03:39.516 biology of aging, the failure of our young biology in 0:03:39.636 --> 0:03:44.316 order to get those diseases. And it's important because we 0:03:44.436 --> 0:03:48.516 want to prevent your aging. And this is really the 0:03:48.556 --> 0:03:50.996 biggest issue that we're talking about. 0:03:51.036 --> 0:03:53.716 Now, tell me a little bit more about that. 0:03:54.276 --> 0:03:57.436 So it's based on the fact that around the world 0:03:57.636 --> 0:04:01.716 in the last few decades, we not only went from 0:04:01.796 --> 0:04:04.636 hoping that there is something we can do, but we 0:04:04.756 --> 0:04:07.356 actually have a promise and we're at the stage of 0:04:07.436 --> 0:04:13.956 realizing a promise. And the promise is in what lifestyle 0:04:14.116 --> 0:04:18.556 decisions we make, what drugs are available right now to 0:04:18.756 --> 0:04:22.476 stunt aging, and the drugs that are being developed now 0:04:22.556 --> 0:04:24.796 and are going to make bigger impact. 0:04:26.116 --> 0:04:28.316 Well, so okay, so let's get into it. So here's 0:04:28.356 --> 0:04:31.076 the three that I know. I feel like the big 0:04:31.116 --> 0:04:38.916 three in terms of what you're talking about, exercise, sleep, well, 0:04:40.076 --> 0:04:46.676 have friends, don't smoke, and eat whole fresh foods. That 0:04:46.876 --> 0:04:49.436 wasn't three, I know, I thought of two more in 0:04:49.516 --> 0:04:49.916 the middle. 0:04:50.996 --> 0:04:55.596 So what you don't do is okay, you know, don't smoke. 0:04:56.956 --> 0:05:01.436 There are four that every one in our field and 0:05:01.476 --> 0:05:06.916 the longevity doctors and everyone would agree on. And that's exercise, 0:05:07.636 --> 0:05:13.556 its diet, sleep, and it's yeah, social connectivity. Okay. Each 0:05:13.636 --> 0:05:18.076 one of those have underlying biology of aging, and each 0:05:18.156 --> 0:05:22.516 one of them is really important when you're young or 0:05:22.636 --> 0:05:27.396 old to optimize. Okay, we used to say maximize, but optimize. 0:05:28.476 --> 0:05:31.716 So those are the ones that we sort of all know, 0:05:32.236 --> 0:05:34.436 right Whether we do them or not is a different question, 0:05:34.396 --> 0:05:39.716 because whose we all lots of people know that those 0:05:39.756 --> 0:05:43.356 things are good, and it is remarkable how good they are, right, Like, 0:05:43.876 --> 0:05:46.916 exercise is so good for so many things in non 0:05:46.996 --> 0:05:50.676 obvious ways. Like sure, cardiovascular exercise is good for your heart, 0:05:50.756 --> 0:05:53.356 that's obvious, but like, why does it make you less 0:05:53.396 --> 0:05:57.156 likely to get cancer? This is an interesting question, right, Hey. 0:05:56.916 --> 0:06:00.716 I just answer that because those are affecting the biology 0:06:00.756 --> 0:06:05.196 of aging a bold claim. Those are affecting the biology 0:06:05.236 --> 0:06:09.076 of aging, and when I'm talking of biology of aging 0:06:09.316 --> 0:06:14.156 is cellular aging. So cells all over the body will 0:06:14.876 --> 0:06:18.796 will be younger or stay younger, and that's why you 0:06:18.876 --> 0:06:23.556 get less cancer and less and less cardiovastro disease. 0:06:23.716 --> 0:06:26.556 When you say cellular age, what is the measure of 0:06:26.636 --> 0:06:28.316 cellular age you're referring to? 0:06:29.196 --> 0:06:34.116 Let me say this way. There are twelve things that 0:06:34.196 --> 0:06:37.716 we call hallmarks of aging. Okay, and I'm not going 0:06:37.756 --> 0:06:39.956 to count them. I might give an example throughout. 0:06:40.156 --> 0:06:43.716 Give me one example. What's the what's a particularly robust example. 0:06:44.196 --> 0:06:48.396 Let's say that one of the problems is we have 0:06:48.556 --> 0:06:52.996 a mechanism of garbage disposal in all our cells. And 0:06:54.516 --> 0:06:58.956 this garbage disposal that's often called autophogy, or the scientists 0:06:58.996 --> 0:07:03.036 will call it autophogy, takes junks that accumulate in our 0:07:03.076 --> 0:07:06.796 cells because our selves is making mistakes in its production. 0:07:07.636 --> 0:07:10.956 And it's taking those things that are really not helpful 0:07:11.236 --> 0:07:15.516 and breaking them down to their component. It's going to 0:07:15.636 --> 0:07:19.676 clean yoursels. Okay, Okay, that's what's going to happen now 0:07:20.476 --> 0:07:23.036 every one of the hallmarks. What you have to show 0:07:23.276 --> 0:07:27.196 is first of all, that it gets worse with aging. Second, 0:07:27.636 --> 0:07:31.276 you can take a young model and make it old. Okay, 0:07:31.476 --> 0:07:34.156 so it was done with autopogy. You knock out autophogy, 0:07:35.076 --> 0:07:39.236 the mice are freaking out. They are becoming older at 0:07:39.276 --> 0:07:42.916 a very young age. But more important, if you fix 0:07:42.996 --> 0:07:48.636 it throughout aging, the mice are not only healthier overall healthier, 0:07:48.956 --> 0:07:52.556 but they also live like twenty percent longer. Okay, So 0:07:52.596 --> 0:07:55.556 that's how you become a hallmark. But the point is, 0:07:55.996 --> 0:08:00.436 whenever you fix one of them, of those hallmarks, you 0:08:00.556 --> 0:08:05.156 really fix also others. Okay. So it's you could take 0:08:05.196 --> 0:08:07.676 one hallmark and show that it's very important, but you 0:08:07.716 --> 0:08:09.876 can do it with each one of them. You don't 0:08:09.916 --> 0:08:12.556 have to do it together. Not that doing it together 0:08:12.596 --> 0:08:15.196 wouldn't be even better, but you don't have to do 0:08:15.236 --> 0:08:15.716 it together. 0:08:15.836 --> 0:08:18.716 You're saying, if you fix one, that one working better 0:08:18.796 --> 0:08:21.276 actually helps to fix the others, right. 0:08:21.156 --> 0:08:23.396 And you can see changes in the others. 0:08:23.516 --> 0:08:28.156 And so when you talk about these, you know lifestyle 0:08:29.116 --> 0:08:36.556 changes like exercise, does your autophogy work better for longer? 0:08:36.716 --> 0:08:38.076 That basically going. 0:08:37.876 --> 0:08:41.876 On exactly, And I'll give you another example. And I 0:08:41.876 --> 0:08:45.516 can stay on autopogy because we don't have enough time 0:08:45.556 --> 0:08:52.916 to cover the twelve. But how does so exercise fixes autophogy. 0:08:53.676 --> 0:08:56.036 The hard one is diet. And I'll tell you why 0:08:56.036 --> 0:09:01.396 I pick diet, because diet is something that's very individual. 0:09:01.596 --> 0:09:05.676 It's it's it's really you know, if I take people 0:09:05.676 --> 0:09:09.316 and say you should become vegetarians, they're going to which 0:09:09.396 --> 0:09:12.596 proteins with carbohydrates, They're going to get fat or some 0:09:12.676 --> 0:09:16.396 of them, and they're going to actually pay. Their health 0:09:16.476 --> 0:09:20.596 is going to be worse. So it's very in the individual. 0:09:20.796 --> 0:09:22.956 How do you choose diet and how you can actually 0:09:23.036 --> 0:09:28.476 stick to a diet. So when I started my studies, 0:09:29.076 --> 0:09:32.756 the experiment that worked in every lab, I took rats 0:09:33.396 --> 0:09:36.356 and half of them got to eat whatever they wanted 0:09:37.036 --> 0:09:40.356 and the other half I gave them forty percent less 0:09:40.356 --> 0:09:44.196 food forty percent less food, so sixty percent of what 0:09:44.236 --> 0:09:49.396 the others got. The rats that got sixty percent of 0:09:49.436 --> 0:09:54.156 the food lived healthier and lived longer. What we did 0:09:54.276 --> 0:09:57.556 is we gave the food in the morning to those animals, 0:09:57.556 --> 0:10:00.676 and they were hungry, and they ate the food, and 0:10:00.716 --> 0:10:04.476 they were then fasting for twenty three more hours. So 0:10:04.676 --> 0:10:09.716 it wasn't only caloric restriction, it was also fasting. In fact, 0:10:09.796 --> 0:10:12.636 when we gave them the food little bit throughout the day, 0:10:13.036 --> 0:10:16.276 they were leaner, but they didn't live much longer, and 0:10:16.316 --> 0:10:19.676 that led to this concept that a lot of us 0:10:19.676 --> 0:10:24.356 are doing, including myself, which is intermittent fasting fast as 0:10:24.396 --> 0:10:29.596 many hours as you can. Because what it does almost 0:10:29.756 --> 0:10:33.996 the major thing that happened, it improves atophagy. This is 0:10:34.436 --> 0:10:37.316 easy for most people to do, not for everyone. It's 0:10:37.396 --> 0:10:40.396 easy for most people to do, and we don't know 0:10:40.436 --> 0:10:44.916 if it extends life, but it certainly improves several factors 0:10:44.956 --> 0:10:49.956 that you can look at, such as weight or metabolism 0:10:49.996 --> 0:10:50.756 and other things. 0:10:50.836 --> 0:10:52.996 So we're talking at nine point thirty in the morning. 0:10:53.556 --> 0:10:54.796 When was the last time you ate? 0:10:56.636 --> 0:11:00.236 I actually finished dinner at six pm yesterday because I 0:11:00.356 --> 0:11:00.996 was traveling. 0:11:01.356 --> 0:11:02.316 What's your usual? 0:11:03.276 --> 0:11:06.156 It's usually eight in the evening when I finished dinner, 0:11:06.476 --> 0:11:10.036 which brings me to noontime the next day. And what 0:11:10.116 --> 0:11:14.356 I'm having. I'm having black coffee and I'm having you know, water, 0:11:14.596 --> 0:11:15.956 but I'm not eating anything. 0:11:16.116 --> 0:11:18.636 How do you feel right now it's been fifteen hours 0:11:18.636 --> 0:11:19.716 since you've eaten. How do you feel? 0:11:19.996 --> 0:11:24.276 I'll tell you the opposite. I was in Europe for 0:11:24.316 --> 0:11:27.676 two weeks and sometimes I had breakfast, and in the 0:11:27.796 --> 0:11:31.996 days that I had breakfast, I was just miserable, but 0:11:32.196 --> 0:11:37.316 by noontime this is really and people in particular people 0:11:37.396 --> 0:11:40.476 my age will tell you that they feel the benefit 0:11:40.556 --> 0:11:47.636 on their basically cognition, their tiredness, their energy throughout the day. 0:11:48.396 --> 0:11:53.476 So you mentioned rats and fasting, and you mentioned mice 0:11:53.796 --> 0:11:57.676 and autophogy, and you know there is that famous line 0:11:57.756 --> 0:12:01.316 mice lie and primates exaggerate, Like to what extent have 0:12:01.436 --> 0:12:04.196 these studies been validated in humans? 0:12:04.516 --> 0:12:07.476 I got a grant from our page together with Dan 0:12:07.556 --> 0:12:09.076 Belski from Colombia. 0:12:09.156 --> 0:12:10.716 Our pages. The government basically it. 0:12:10.996 --> 0:12:15.196 Is the government right, and the government totally bought into 0:12:15.876 --> 0:12:20.476 targeting aging and health spin but they funded us for 0:12:20.596 --> 0:12:25.556 a simple reason. There are four drugs probably more that 0:12:25.676 --> 0:12:30.796 we know target aging. And when you put those drugs 0:12:30.836 --> 0:12:35.996 on cells, okay, they change the hallmarks of aging utophagy, Okay, 0:12:36.476 --> 0:12:40.036 when you give them to animals, they live healthier and longer. 0:12:40.476 --> 0:12:43.596 And in clinical studies, although those drugs were designed for 0:12:43.636 --> 0:12:48.716 a certain disease, they also prevent other diseases. And although 0:12:49.076 --> 0:12:52.996 they were developed for a certain disease, they prevented overall 0:12:53.036 --> 0:12:56.876 mortality and not the disease specific mortality. So we take 0:12:57.036 --> 0:13:02.156 studies that were already ended, and we're asking a simple question, 0:13:02.276 --> 0:13:06.236 not only what are the biomarkers of aging, but which 0:13:06.316 --> 0:13:08.516 one are changing with intervention? 0:13:09.156 --> 0:13:12.836 So what exactly is the study that you're doing. 0:13:13.236 --> 0:13:18.596 We we take blood samples that already exist because the 0:13:18.676 --> 0:13:23.116 trials are done of four drugs, and we're looking at 0:13:23.156 --> 0:13:26.076 what happened to each individual, whether he was on a 0:13:26.156 --> 0:13:30.436 drug or on a placebol within the first year of therapy. 0:13:30.476 --> 0:13:32.556 And to be clear, when you say drugs blood samples, 0:13:32.596 --> 0:13:34.236 do you mean the actual blood or you just mean 0:13:34.276 --> 0:13:37.076 the tests that were done on those samples in previous tests. 0:13:37.196 --> 0:13:39.876 No, no, no, no, we have to do it's it's 0:13:39.916 --> 0:13:44.156 totally new. We're taking the blood and using. 0:13:44.396 --> 0:13:46.676 So people store the blood from trials. These are trials 0:13:46.756 --> 0:13:48.476 that are years old and the blood has just been 0:13:48.516 --> 0:13:50.316 sitting there in the fridge waiting for you to come 0:13:50.356 --> 0:13:54.236 in the free the freezer. Yeah, of course, and so 0:13:54.236 --> 0:13:59.036 so and and the drugs are what theyre It's met foreman, rapamycin, 0:13:59.796 --> 0:14:02.116 GLP one, some GLP one drug. 0:14:02.436 --> 0:14:04.476 And s GILT two inhebitors. 0:14:04.596 --> 0:14:06.196 What's that last one. I don't know what that last 0:14:06.196 --> 0:14:06.516 one is. 0:14:07.916 --> 0:14:11.236 This is a very potent drug against aging. It's developed 0:14:11.236 --> 0:14:15.516 for diabetes for sigia in volcana are the common name. 0:14:15.556 --> 0:14:19.276 There are five five manufactures of this drug. 0:14:19.676 --> 0:14:21.756 So there's the blood in the freezer and you're taking 0:14:21.756 --> 0:14:23.396 it out of the freezer and you're looking at these 0:14:23.436 --> 0:14:25.956 twelve different hallmarks of aging and you're seeing how they 0:14:26.076 --> 0:14:28.836 change over the course of the year and comparing those 0:14:28.956 --> 0:14:33.276 changes for people in the drug arm of these trials, 0:14:33.276 --> 0:14:35.916 in the treatment arm versus the people in the placebo arm. 0:14:36.556 --> 0:14:40.196 So for each individual before and after treatment, we're going 0:14:40.196 --> 0:14:43.876 to have tons of data and we're going with AI 0:14:44.116 --> 0:14:48.956 to reduce it to what is common for all those drugs, 0:14:49.916 --> 0:14:54.476 what has commonly changed with treatment between all those drugs, 0:14:54.716 --> 0:14:56.876 and this is likely to get to give us the 0:14:56.916 --> 0:15:01.236 best clock to use in a clinical practice. 0:15:02.956 --> 0:15:06.076 And so basically, you want to find something that is 0:15:06.116 --> 0:15:10.356 easy to measure or relatively easy to measure from a 0:15:10.356 --> 0:15:12.756 blood test, say so that you can look in a 0:15:12.756 --> 0:15:17.476 blood test and ideally find someone's biological age so to speak. 0:15:18.436 --> 0:15:22.876 Correct Again, we can do the biological age quite good now, 0:15:23.436 --> 0:15:27.556 but what is change what has change when you actually 0:15:27.556 --> 0:15:32.036 give a treatment that targets the age, that's the major point. 0:15:32.076 --> 0:15:37.036 But you're assuming that bigs into that assumption is that 0:15:37.076 --> 0:15:40.196 all these drugs in fact slow aging. That like, that 0:15:40.276 --> 0:15:43.356 is a conclusion that has to be true for this 0:15:43.436 --> 0:15:44.876 study to make sense. Is that right? 0:15:45.236 --> 0:15:48.796 Well, it's the other way around. Those drugs did four 0:15:48.876 --> 0:15:52.036 things right, each one of them. You put them in cells, 0:15:52.476 --> 0:15:55.156 They make the cells younger. You give them to animal, 0:15:55.676 --> 0:15:59.236 they live healthier and longer. You gave them already to people. 0:15:59.316 --> 0:16:03.836 Those are our studies that had outcomes, and you show 0:16:03.956 --> 0:16:05.996 that you give it for one thing and you prevented 0:16:06.076 --> 0:16:09.716 other things, and that it changed overall mortality. 0:16:10.396 --> 0:16:13.436 That last part is that unambiguous. Like I wish I 0:16:13.476 --> 0:16:14.316 knew the data better. 0:16:14.396 --> 0:16:18.916 Oh, like the studies, I mean, it's absolutely amazing. Let 0:16:18.916 --> 0:16:21.476 me give you a flavor for the drug that you 0:16:21.516 --> 0:16:25.516 didn't hear about as Gilty two inhibitors. S. GILTY two 0:16:25.556 --> 0:16:29.196 inhibitors were developed for diabetes, and in the diabetes trial 0:16:29.676 --> 0:16:33.276 it became apparent that they prevent cardiovas to disease and 0:16:33.396 --> 0:16:37.636 kidney disease. Yeah, but then nephrologies came and did a 0:16:37.716 --> 0:16:40.676 study and just to give you a taste, they took 0:16:40.756 --> 0:16:44.756 four thousand people, half of them are placible and in 0:16:44.876 --> 0:16:48.676 forty two non diabetic just people with impaired kidney function, 0:16:49.436 --> 0:16:53.436 and in thirty two months they showed that they prevented 0:16:53.476 --> 0:16:57.876 forty percent of deteriorating of kidney function, forty percent decrease 0:16:57.916 --> 0:17:01.316 in cardiovas to disease, and forty percent decrease in overall mortality. 0:17:01.636 --> 0:17:05.556 So it's circular. But what other explanation do you have 0:17:05.676 --> 0:17:08.556 for a drug that actually changed the hallworks of agyp. 0:17:12.556 --> 0:17:26.076 We'll be back in just a minute. Shall we talk 0:17:26.076 --> 0:17:27.756 about your genetics work? 0:17:28.396 --> 0:17:28.716 Sure? 0:17:30.876 --> 0:17:33.316 What have you learned from studying the genes of people 0:17:33.316 --> 0:17:34.356 who live to one hundred? 0:17:35.436 --> 0:17:37.876 So first of all, I want to tell you that 0:17:38.036 --> 0:17:42.076 my fear when I did the study was what if 0:17:42.116 --> 0:17:47.476 I find that all those hundred years old have gotten 0:17:47.596 --> 0:17:51.436 disease like everyone after the age of sixty, they got 0:17:51.436 --> 0:17:56.036 disease and just lived longer with diseases. And what we 0:17:56.236 --> 0:18:03.236 found is that they live twenty thirty years healthier. So 0:18:03.276 --> 0:18:06.316 it's not only they lived longer, they live healthier, and 0:18:06.356 --> 0:18:09.236 that wasn't really the big thing. The big thing is 0:18:09.276 --> 0:18:11.796 that they had what we call a contraction of morbidity. 0:18:12.156 --> 0:18:14.156 They will sick very little time at the end of 0:18:14.196 --> 0:18:18.836 their lives. The CDC may rest in peace or be 0:18:18.996 --> 0:18:24.476 resurrected whatever. The CDC have shown since nineteen ninety three 0:18:25.076 --> 0:18:27.556 that people who die over the age of one hundred 0:18:28.076 --> 0:18:31.716 have third of the medical cost in the last two 0:18:31.756 --> 0:18:35.316 years of their own Interesting, then people who die at seven. 0:18:35.076 --> 0:18:37.396 So they die, they live a long time, and then 0:18:37.436 --> 0:18:40.596 they die fast. That's the dream exactly. 0:18:40.636 --> 0:18:42.076 So that's what we want. 0:18:42.076 --> 0:18:45.156 Right, that's good news for people with the genes that 0:18:45.236 --> 0:18:49.636 cause you to live a long time. Regarding your genetic studies, 0:18:49.676 --> 0:18:54.436 I mean, is there any I don't know people in 0:18:54.476 --> 0:18:57.276 my family don't live to one hundred, Like, am I screwed? 0:18:57.596 --> 0:18:59.396 Does that matter for me that study? 0:18:59.876 --> 0:19:03.116 No, the opposite. You're the one who's going to benefit. 0:19:03.276 --> 0:19:05.996 We don't have anything for those hundred years old, Okay, 0:19:06.436 --> 0:19:10.716 because that's it. So two of those genes have already 0:19:10.756 --> 0:19:14.036 been developed to drugs that past phase three trial. 0:19:14.516 --> 0:19:17.596 That that past phase three meaning the FDA is they're 0:19:17.676 --> 0:19:20.476 up for approval at the FDA, right, Yeah, tell me 0:19:20.516 --> 0:19:21.596 about those drugs. 0:19:21.836 --> 0:19:26.956 So one drug is called the CDP INHIBITORQUE. It's a 0:19:27.076 --> 0:19:32.276 drug that basically increase your good cholesterol and decrease your 0:19:32.316 --> 0:19:35.756 trigue glycerides. But that's only part of what it's doing. 0:19:36.116 --> 0:19:39.316 And so when they're doing a phase three trial of 0:19:39.316 --> 0:19:41.996 this drug, what is the end point? What are they 0:19:41.996 --> 0:19:43.756 actually trying to show that it does? 0:19:43.876 --> 0:19:47.636 So they're not doing it for aging. They came to 0:19:47.756 --> 0:19:53.556 me because my studies showed that probably inhibiting CDP safe 0:19:53.596 --> 0:19:56.196 because they are one hundred years old. Fourteen percent of 0:19:56.196 --> 0:19:59.276 one hundred years old have these genes that increase their. 0:19:59.316 --> 0:20:02.116 As opposed to how many people in the population. 0:20:01.636 --> 0:20:03.836 At large three to four percent. 0:20:03.876 --> 0:20:06.636 Okay, so it's like four times as common or something. Right, 0:20:07.556 --> 0:20:11.116 Is that drug being developed as a cardiovascular drug? Like, 0:20:11.116 --> 0:20:12.276 what are they testing it for? 0:20:12.996 --> 0:20:16.836 It's been developed as a cardiovas or drug, but there's 0:20:16.996 --> 0:20:21.716 evidence that it's also prevent cognitive decline, which was our 0:20:21.796 --> 0:20:23.956 major claim around these drug. 0:20:24.076 --> 0:20:26.116 Are they testing it for that? That's a hard indication 0:20:26.236 --> 0:20:26.556 to get. 0:20:26.716 --> 0:20:28.716 Yeah, yeah, they tested and their data. 0:20:29.476 --> 0:20:33.356 So you've talked about these promising drugs, most of which 0:20:33.396 --> 0:20:37.396 are approved by the FDA for something met Foreman's approved 0:20:37.436 --> 0:20:40.676 for diabetes, GLP one drugs are approved for weight loss. 0:20:41.316 --> 0:20:43.796 I know that you've talked in the past about getting 0:20:43.956 --> 0:20:47.956 a broader FDA approval. Specifically, you were trying to get 0:20:47.996 --> 0:20:51.436 funding for this study called the tame trial where you 0:20:51.556 --> 0:20:54.676 randomize people to get met foreman or placebo, and then 0:20:54.836 --> 0:20:57.196 the idea was you would follow them for several years 0:20:57.236 --> 0:20:59.996 and see if the people getting met foreman had a 0:21:00.036 --> 0:21:03.796 lower rate of things like cardiovascular disease and cancer and 0:21:03.916 --> 0:21:06.996 overall mortality, just do they die less. So is the 0:21:07.036 --> 0:21:10.276 idea that if you do that study and you have 0:21:10.596 --> 0:21:14.756 a positive outcome, like, what would the FDA say, what 0:21:14.756 --> 0:21:17.396 would the indication be? Would it be give metform into 0:21:17.436 --> 0:21:19.516 everybody over a certain age or what? 0:21:22.916 --> 0:21:26.836 No? No, the answer is no, because the study population 0:21:27.116 --> 0:21:30.516 are people over the age of sixty five that are 0:21:30.676 --> 0:21:35.756 already not doing not doing well. Not that people will 0:21:35.796 --> 0:21:36.956 become centenarians. 0:21:37.036 --> 0:21:39.756 Okay, uh, because you need I mean for the study 0:21:39.836 --> 0:21:42.516 to work, you need some people to get sick. Frankly, 0:21:42.596 --> 0:21:45.156 if everybody on both sides stays healthy, you don't learn 0:21:45.196 --> 0:21:46.156 anything exactly. 0:21:46.516 --> 0:21:49.876 And it doesn't make sense to take forty years old 0:21:49.916 --> 0:21:53.276 and do the study and finish it in forty years 0:21:53.356 --> 0:21:57.476 to ever result. It's but the FDA is working with 0:21:57.676 --> 0:22:03.836 us on trying to get other indications that don't take 0:22:03.996 --> 0:22:05.036 so long to. 0:22:06.076 --> 0:22:08.196 How long, how long and how big would that study 0:22:08.316 --> 0:22:10.436 need to be to be properly powered. 0:22:11.036 --> 0:22:14.236 We had three thousand people for four years. 0:22:14.276 --> 0:22:15.116 That was the design. 0:22:15.716 --> 0:22:15.916 Yeah. 0:22:15.956 --> 0:22:17.516 And it's just hard to fund because this is a 0:22:17.556 --> 0:22:20.476 generic drug. It's cheap, which is good if you want 0:22:20.516 --> 0:22:22.756 to take it, but it's bad because there's no drug 0:22:22.796 --> 0:22:24.596 company that can make a billion dollar selling it, so 0:22:24.636 --> 0:22:25.796 they're not going to pay for the trial. 0:22:26.196 --> 0:22:29.196 Right, And we had funding, and then there was COVID 0:22:29.236 --> 0:22:31.356 and then we lost, you know, the funding. 0:22:34.236 --> 0:22:35.556 Tell me about supplements. 0:22:37.396 --> 0:22:39.916 I'll start with a good thing. Supplements are good for 0:22:39.956 --> 0:22:40.676 the economy. 0:22:41.276 --> 0:22:44.236 Yeah, okay, because people spend a lot of money on them. Yes, 0:22:44.596 --> 0:22:44.836 you know. 0:22:44.916 --> 0:22:49.196 For me, supplement means that you measured something and it's 0:22:49.236 --> 0:22:52.756 slow and you give it back, right, But that's not 0:22:52.836 --> 0:22:56.516 how supplements are done. Supplements are pecking together one hundred 0:22:56.596 --> 0:22:59.916 things or several things and giving you an also in 0:22:59.956 --> 0:23:04.276 the bottle they say take two. Okay. There's no clinical 0:23:04.396 --> 0:23:08.436 data on supplements. Okay. The FDA approves supplement not based 0:23:08.476 --> 0:23:14.676 on clinical data. So what marketing of supplement is a 0:23:14.756 --> 0:23:19.236 total hope? Okay, there's no promise. Not only that, the 0:23:19.276 --> 0:23:24.636 most dangerous things is multi supplement that you take them together. Okay, 0:23:25.116 --> 0:23:29.196 and you think they're additive, but they're antagonistic many times, 0:23:29.236 --> 0:23:33.236 because if they're biologically important, you're going to find interactions 0:23:33.236 --> 0:23:36.276 that you don't like. We actually know that people who 0:23:36.276 --> 0:23:40.716 take multi supplements have increased mortality in spite of the 0:23:40.796 --> 0:23:43.036 fact that they are the people who also exercise and 0:23:43.116 --> 0:23:44.316 diet very often. 0:23:44.356 --> 0:23:47.276 When you say multi supplement, like a multi vitamin or 0:23:47.276 --> 0:23:47.716 what do you. 0:23:47.676 --> 0:23:52.316 Mean like multi vitamins, let me ask. 0:23:52.196 --> 0:23:57.516 You another question. So the field that you are in 0:23:59.196 --> 0:24:01.436 is full of and has always for all of history 0:24:01.476 --> 0:24:05.316 been full of cranks and charlatan's. You're a doctor at 0:24:05.356 --> 0:24:08.836 a medical school, Like, how do you deal with that? 0:24:09.116 --> 0:24:10.916 And do your colleagues think you are a crank and 0:24:10.956 --> 0:24:11.556 a charlatan? 0:24:11.596 --> 0:24:15.276 Respectfully, what you said was exactly the sentiment when I 0:24:15.356 --> 0:24:20.196 got several major organizations to meet in New York and say, hey, 0:24:20.316 --> 0:24:22.596 we have a lot of progress, and we have a 0:24:22.636 --> 0:24:23.316 lot of noise. 0:24:23.436 --> 0:24:24.716 When was this? When was this? 0:24:25.116 --> 0:24:27.756 That was two years ago? Two years ago, and we 0:24:27.836 --> 0:24:31.196 did something that's so unusual for a bunch of scientists. 0:24:31.316 --> 0:24:35.236 We said, you know what, we really don't know what 0:24:35.356 --> 0:24:39.396 to do. Why don't we take a branding company and 0:24:39.676 --> 0:24:42.796 let them deal with it? And this is the best 0:24:42.796 --> 0:24:45.516 thing we did because the branding company actually worked. It 0:24:45.956 --> 0:24:48.836 was hundreds of thousands of dollars and we're still working 0:24:48.876 --> 0:24:49.556 with them. 0:24:49.836 --> 0:24:52.676 It makes me nervous when you say branding company. I'm 0:24:52.716 --> 0:24:54.996