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Meds, Dr. Barzilai | The Future You | Men's Health
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00:00So with this robust series of clinical studies behind metformin showing its positive impact on
00:05aging, you know, a lot of us are looking online and seeing things in our social feeds about
00:10miracle drugs. And there are lots of different names that are being thrown around. Are there
00:14any other pharmaceutical drugs that have been shown to have that sort of impact or a metformin
00:21size impact on aging? Welcome to the Future You, a new series by Men's Health, where we talk to
00:26the leading experts in health and longevity to help you live longer and stronger. I'm
00:30your host, Rich Dormant. In this episode, we're talking with longevity expert Dr. Nir Barjulai
00:35about life-extending medications and intermittent fasting. And we have a paper that just came
00:40in March where we have 12 drugs that are FDA-approved. Okay, so when I say FDA-approved, safety, efficacy,
00:48they've been used for a while. And also, when you give it to animals, they live longer.
00:53Can you name the 12? Yeah, I can make the 12s. But actually, 10 of them, it's a scale of 12.
00:59And four of them get 10 and above. And those are the four. Are you ready? Number one. Number one
01:08is a class of drug that's also for diabetes that's called SGLT2 inhibitors. This is a fascinating drug
01:19drug that is now used mainly in non-diabetic individuals. Why? Because it prevents decrease
01:25in kidney function and decrease in cardiovascular function. Okay, two diseases of aging. So it was
01:32developed for diabetes, those effects. And not only that, you give it to population in a clinical
01:37study and it prevents overall mortality. What more do you need to show that it affects aging,
01:43that you decrease mortality. Those people live less, more healthy, and die less.
01:50The second is metformin. The third is really a surprise. It's a drug that usually women get when
01:58they have severe osteoporosis. It's called biphosphonates. And it was first, the first time I realized
02:05was several years ago when there was an interesting paper saying women who are biphosphonate and go to ICU,
02:12they don't die. Okay. And then we started fishing and seeing that actually when you give it to animals,
02:18they live longer, that they affect lots of those hallmarks of aging. And actually in clinical studies,
02:24they reduce overall mortality. So that's one. And you might expect the last one that made it
02:31is those MP kind of drugs, kind of back to the caloric restriction ID, right? So look, so first
02:40of all, those drugs were designed for diabetes. I'm a diabetologist. I'm in clinic several times a month,
02:49tomorrow morning included. I've been using these drugs for eight years. It's a miracle drug. It
02:55changed the face of diabetes. So you give it to diabetic patient and it treats their glucose,
03:01but they also decrease weight and it takes away their diabetes for most of them for a long period
03:07of time. So it was of course repurposed to obesity. So it was developed to diabetes. Now it's used for
03:15obesity. Why obesity is important? Because obesity drives aging. Okay. During the COVID,
03:22you could see that, okay, if you're over the age of 80, you had 180 times more chance of dying than
03:31if you were 20. But if you had obesity, you had eight times more chance of dying at any age.
03:37Okay. Obesity drives aging. So it was purposed to obesity. And then it was shown that you're treating
03:45obesity, but you're delaying cardiovascular disease. This week in your England Journal of Medicine,
03:51you take this drug and it prevents the progression of Parkinson's. So it's another drug that has
04:00effects through obesity, but it actually affects geroscience. It affects the hallmarks. And it's
04:08one of the drugs, one of the tools we have to repurpose. Any doctor can decide, you know,
04:16you're older now, you're obese, we should first take care of you, get you to a normal weight, and then
04:23maybe we switch you to metformin. But, you know, but it's a tool. So there are the four heavy hitter
04:29tools in the drug category. What are some lifestyle things? You know, you'd mentioned caloric restriction,
04:37which I think most people are not super interested in. But what about intermittent fasting,
04:42which is, again, it's something that has really taken a hold, both within and without the dieting
04:47culture over the past, you know, 10 years. Right. So, okay. So back... I should also add,
04:52you're on like hour 17 of fasting. Yes? Yes. Right now? You haven't eaten in 17 hours. Yes. Are you
04:58hungry? I get better with fasting. Are you hungry? No. Amazing. Okay. So remember, I told you this
05:06caloric restriction story, and I left out something really important. I said that people said you should
05:11have less for breakfast, lunch, and dinner. But that's not what we did with our animals. We would
05:17bring them the food in the morning. And they're hungry. They eat all the food in 20 minutes. Now
05:23they're fasting for 23 more hours. So it's not... We didn't do only caloric restriction. We did caloric
05:30restriction and fasting. When now we give the food throughout the day, they're thinner, but they
05:37don't live much longer. So the fasting is part of what's responsible for the aging part, for the
05:44longevity part. And that's where intermittent fasting came from. So what's going on? What do we
05:50know about what's happening inside the body that's leading to these results? So that's a better question
05:56because this idea, this invention of 16 hours, eight hours is all a creation based on not data,
06:04no data. It's like 10,000 steps, right? It's just a nice, easy way of thinking about 16 hours of
06:09fasting. 10,000 steps already have some data. And intermittent fasting has data in the sense
06:16that there are clinical studies, but they're short. They're small and short. You're not going to have,
06:23oh, it prevented mortality by 20%. Okay. But there are reasons to believe that they're matching
06:30what we measure in humans seems to be similar to what we are measuring in animals. And it's all
06:38improvement for our markers of aging. So that's what we have for now. However, I'll tell you, so since
06:47I'm doing that, I've been looking at what is, why am I improving so much on so many ways? And one of
06:55the things, certainly that metabolically I'm better, my hemoglobin A1c, which is a measure of glucose,
07:02has been low and stayed low for the last years that I'm fasting. My weight has been better.
07:09My exercise capacity has increased. So there are biomarkers, you know, there are markers that I
07:18can see what happens. But as far as mechanism, I thought that it would be because I produce ketones
07:25and you raise the ketone question because of diets and ketone diets. And I'll tell you, I've been
07:32measuring even up to 20 hours and 24 hours, I don't get ketones. And my insulin is low, but not low
07:40enough to really switch me totally from carbohydrates to fat. We were going to start a study
07:48before COVID. So all the funding is gone and everything is gone. But we're going to try and
07:54take young and old people because it's going to be different biology, fast them for almost 24 hours
08:01and measure biologically, you know, those hallmarks on cells and others and in the plasma and to
08:09really measure the time course of what happens. And we didn't, and probably somebody will do it
08:15eventually. But I know that I'm benefiting for it, but not because I'm with ketones, okay? But
08:23other things can happen. There is a process called autophagy that is very important for aging,
08:28one of the hallmarks of aging. And we think that's actually improving after time.
08:34And what is that? What is autophagy?
08:36Autophagy is a cool thing. So in every one of our cells, things go wrong also. We can have proteins
08:45that are not folding well and they could accumulate except that there's a garbage disposal mechanism
08:54that is also green energy. Takes those proteins, puts them somewhere, do the garbage, and then you
09:00can actually use, again, the nutrients to build something better now. This process has declined
09:06with aging and we can fix it. In Einstein, one of the most prominent researchers in the field is at
09:12Einstein. She fixes it so that the animals live longer and healthier. And now she has a biotech where
09:17they're actually developing a drug to do that. So we can measure autophagy and see if autophagy has improved
09:26because this is a good marker for better health. So we don't know the time course and it's probably
09:33individual, okay? We don't know if it's better to skip breakfast or to skip dinner, right? Or something
09:40like that. We don't know if 12 hours is as good as 16 hours. We don't know all that. We do know that men
09:48who do it, they lose more weight than women do, okay? Aging and sex is a very complex thing. Not
09:58everything that helps men helps women. That's a thing that we're trying to get our arms around. But basically,
10:06there's benefit for both sexes if they do it, a clear benefit. But does it increase a lifespan or does
10:15it prevent diseases? We really don't know in a convincing way. So you have a lot of irons in the
10:22fire, lots of exciting things coming down the road in various stages of development. What are you most
10:28excited about? What's getting you out of bed and sort of driving you to your lab every day?
10:33So look, we discuss what we're doing to get to 115. Is 115, does it have to be the end?
10:47Probably not, but I don't think in my time, okay? But this is how we're looking at the field.
10:54You can take an egg of a 50-year-old woman and a sperm of a 90-year-old man and you can fertilize the egg
11:05and have a baby. When this baby is formed, it's really stem cells. Those stem cells don't remember
11:14the age that you could actually measure on the sperm and egg. It goes to zero, okay? We don't remember this
11:21age that we can measure so well on us. We don't remember this age. We go to zero. We figured out
11:28how to do it in this instance. And now we're working in the lab to see how we can do it
11:34to certain cells, organs, and to whole body. So in my mind, and again, let's put it 50 years from now,
11:41because I'm not going to be around, so you can blame me. But you can take a 20-year-old and give them
11:48a treatment, and maybe it'll be IV treatment, and you repeat it every few months or every few years,
11:55and you'll kind of have a Peter Pan that doesn't get old or gets old slowly and will, on its own,
12:05you know, live beyond these 115 years. But am I obsessed with it? No. No, I like this and I follow this.
12:17But there are three projects that are really important for me because they hold the field. One of them
12:26is the metformin issue, because the metformin for me is a tool to show the FDA that aging
12:36can be targeted, and to get an approval for this. I'm stopping short of saying aging is a disease,
12:48okay? It's a whole other conversation. We don't need to use that. If we show to the FDA that, hey,
12:54we treat a drug and we prevent a cluster of age-related diseases or mortality, they'll give
12:59an indication of that, and everybody will know what it is, and we'll do it, okay? So this is one thing.
13:05It's called the TAMES study. The second thing that holds us to many extents is there are no good
13:14biomarkers for aging. Aging is not like having a cholesterol that also causes, you know, heart
13:22disease, and you just need the cholesterol and lower that, and you know the outcomes. Or to treat blood
13:27pressure, you get the blood pressure down. Aging is more complex than that, and we have a lot of tools
13:35to increase our understanding and to hone on biomarkers, but there's a specific program that
13:40I'm dealing with. It's not only to see the biomarkers, but to have biomarkers that change
13:48when you do the interventions, whether it's diet or exercise or sleep or social connectivity or metformin
13:55or other drugs. You want to show that you actually change the rate of aging with the biomarkers. The
14:02biomarkers show, yes, you've done it, like you have the cholesterol as a proof that you've done
14:08something about it. And this would bridge the gap between your chronological age, what it says on your
14:12driver's license, versus your biological age, which is how old your body is. Correct, correct. So
14:19absolutely. And you're right. I should have started with that. Okay. So you'll get your age. Okay. And
14:27so it's important, for example, if you're 50 years old, but you're really 40 biologically, you don't
14:34need to do colonoscopy. Okay. Or other things. So it's important to get your bio. And if you're 60,
14:40boy, do you need to have a workup now? So that's certainly a thing. The biological and chronological age,
14:45we all know it's true, right? Maybe not in our friends, but if you look at their parents,
14:53you know, some people are aging slower and some other. I mean, I'm looking at the centenarians,
14:58they don't look 100 years old, which I'm quoting as saying that, but that's how they look like.
15:04Well, you look amazing for 30, I should say. I'm 100 actually. Okay. Even better.
15:09So it's not, what you want is, let's say you're older than your age and we want you to exercise,
15:17to take metformin maybe. We want to show you that this biomarker becomes younger now. Okay. That
15:22you're actually now 55 and not 60. Okay. So what we're doing is we're going to those studies that
15:29were done with the medicines that I talked about before. And we're taking samples within a year of
15:36therapy and measuring hundred thousands of biomarkers to see what have changed with each
15:42treatment and also what's commonly changed in each period. What is the aging part of that? And those
15:49are the biomarkers we want to develop because at the end, our medicine will be, you go, you even don't
15:57go to the doctor. You have technology and app that will manage you and tell you, you have to do that and
16:03you have to do this. And every time, so often you have to take tests. And if you need the doctor, you'll
16:08have a doctor, but we want to prevent you from doing doctor. We want you to spend time on your health
16:16so that you don't spend time on your diseases. This is what we're trying to do. It's not only about the
16:22elderly. For example, people who survive cancer because we gave them radiation and chemotherapy, which
16:30means we accelerated their aging, they get into trouble. Kids get heart attack when they're 35.
16:36Women after breast cancer, some of them are really have aged significantly. They need help. People with
16:42HIV get diseases 10 years before their, their class. They need help. People who are disabled. Okay. And so
16:52they don't, they don't move. They eat more. They get into trouble. I would actually say poor people in,
16:59particularly in the United States, in every city, the poor versus rich, they have a 20, 30 year
17:04life expectancy difference. They also need help. And if we want to go to Mars, we have to solve aging.
17:12We're not going to get there if we don't solve aging because we'll get a disease on the way there
17:16and we'll never make it back. So there's a lot of reasons that we need to do it. And the sooner,
17:22the better, the better. First day in medical school, we are taught do no harm. Okay. Think about it.
17:30Any patient that comes to you, half of the class will say, I don't really want to do anything for you,
17:35but I have pain. Well, you know, Tylenol, one of a hundred thousand impairs liver function,
17:41so get over it. Right. This is what we're taught to be very conservative. The second day of medical
17:47school, it gets worse. They tell you there's no never and there's no always. So not only you're
17:53conservative, you're unsure. Okay. And, and this carries on because people are asking me, okay,
17:59what happens if metformin saves hundred people and kill three? Okay. What do you answer that? I think
18:06I'll save a hundred people, but, but it's a real issue because every, everything has a trade-off.
18:12Everything I told you, there's somebody will say, no, that killed me. Okay. But the evidence are
18:18evidence from population and we have to get better at understanding it. And so, but this conservatism
18:26is something that we're, we're fighting because we want more people to treat you with gerotherapeutics,
18:33whether it's the exercise and stuff, whatever it is, we want more people to be treated because this
18:39is good for you. It's good for the economy and we have to do it and do it sooner rather than later.
18:46So if nothing else, people should be speaking with their primary care physicians,
18:50with their geroscientists, with their gerophysicians about these, these medicines,
18:55about these drugs. It might not be right for them, but they should start the conversations that they
18:59haven't already. Again, you said it better than me. I think we got everything. Thank you so much as
19:05always for coming in to speak to us. There's nobody else in the world who understands the stuff better
19:11than you. And thanks to you, our audience knows a little bit about it as well. So thank you so much.
19:16And here's to better aging for all of us.
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