In this episode, we talk to anti-aging researcher and entrepreneur, Dr. David Gynning. We talk about what he's doing in the lab, how he thinks about aging, and what he thinks we can do to slow it down or at the very least stop it from happening. We also talk about some of the things you can do in your everyday life to make your life a little bit shorter, or at least a little better than it has been in the past. If you want to know what you should be doing in your life to slow down aging, this episode is for you. This is a fascinating subject, and one that's been around for a long time, and we think we've got a good idea on how to do something about it in humans. In this episode we talk with Dr. Gynnings about his research, his family, and the research he's been doing in his lab for the past 20 years, and why he thinks that we can stop aging. We hope you enjoy listening to this episode and that it makes you think about how much longer you have got left in this life. Happy New Year, everyone! Thanks for listening, and Happy 2020! XOXO, Eben and Joe - Tom Bell and Elyssa Music: "Good Morning" by Suneaters, "Goodbye Outer Space" by Fountains of Bakersfield, "OuterSpace" by Joseph McDade, "Coming Soon" by Lizzie, "Thank You" by Pizzi, "Let's Talk About It" by The Good Morning Project, "It's Your Day Off" by Chacho, "The Good Morning Podcast" by Jeff Perla, "Don't Tell Me About It (feat. , "I'll See You Soon" and "Wish You Were There" by Mr. Tom, "I'm Working On It" by Sisyphus, "We'll Figure It Out How to Stop Ageing" by Kevin McLeod, "No One's Got It Out" by Jay Sheeran, "Your Day Off, I'll Figure it Out How To Stop Aging? , and "You'll See It Out, You'll Have It's My Best Day" by Dr. Joe, "You're Not Working It Out," "I Can't Stop It (I'll Have A Good Enough," "It'll Get Better Next Week"
00:01:35.000But that seemed to be good, because a study came out about a couple of weeks ago, at least in mice, that it's not what you eat, it's when you eat that's most important for longevity.
00:01:53.000But you need a period during the day, at least if you're a mouse, probably if you're a human, where you're hungry.
00:01:59.000And that puts your body in a defensive mode.
00:02:00.000These are the things that we've been studying in my lab for the last 20 years.
00:02:04.000What are the processes that diet and exercise do for us that keep us healthy and why does calorie restriction and intermittent fasting make animals live so much longer?
00:02:14.000And we think we've figured out a large part of how that works and now we're mimicking that with molecules.
00:02:20.000Is the idea that you can mimic it with molecules and it will be as effective as intermittent fasting?
00:03:21.000If we give our latest molecule, called anamn, to a mouse and we exercise it, it'll run even further than it could with either of those alone.
00:03:31.000So it's not an excuse to sit around and just eat chips and watch TV. It augments a healthy lifestyle, gets you further than what you could get naturally.
00:03:40.000So are you seeing a benefit in addition?
00:03:43.000So is the idea to compound all those things together?
00:05:16.000It's related to NR, which is sold by a bunch of companies.
00:05:21.000NR? Yeah, nicotinamide riboside is a supplement that raises the levels of a molecule called NAD. I feel like I should make a shopping list.
00:05:47.000But as we get older, we lose NAD. So by the time you're 50, like I almost am, you have about half the levels of what you had when you were 20. So that's not good.
00:05:57.000And these sirtuins, they don't protect the body without high levels of NAD. So what NMN does, and this other molecule called NR, which both you can get on the internet, they boost the body's levels of NAD back up to youthful levels again.
00:06:12.000And if we give them to mice, these molecules to mice or even to worms or yeast, they live longer and they're super healthy.
00:06:19.000Now, what level, like how many milligrams are you taking of these things?
00:06:24.000So, yeah, NMN is something I get from myself.
00:07:03.000I have a few kilos left over from clinical trials in my basement.
00:07:08.000So, yeah, that's going to last me a few decades.
00:07:10.000And then I also take, at night, some metformin, which is probably the most radical thing that I take, which is a prescribable drug for diabetes.
00:07:35.000M-E-T? F-O-R-M-I-N. And so out of studies of 10,000 people and more, it's been shown that people who take metformin, even if they have diabetes, are protected against other diseases of aging, even frailty.
00:07:50.000And so most scientists, if you ask them in my field, will say, yeah, metformin is likely to extend your lifespan.
00:07:56.000It's just that the FDA doesn't let you have it for aging, because aging isn't a disease yet.
00:08:02.000So do you have to get diabetes to get it, or do you have to get a sneaky doctor?
00:08:06.000Well, I wouldn't call it a sneaky doctor, but the doctor typically has to be convinced because they don't keep up with the literature.
00:08:54.000So this is the great thing, is that over the last 20 years, we have figured out, we scientists have figured out, that there are universal regulators of aging, from yeast to worms to mice and in humans.
00:09:05.000And there are three main pathways that we've figured out respond to what we eat and how we exercise.
00:09:10.000And one of them is called AMPK. And this is a target of metformin.
00:09:16.000And so when I take metformin, I'm activating my AMPK, which will send out the troops.
00:09:22.000The sirtuins I've mentioned, that's the second of the pathways.
00:09:26.000And so I take NMN and resveratrol for that.
00:09:28.000And then the third one is called mTOR, which is a pathway in the body that responds to how many amino acids, how much meat you're eating.
00:09:36.000And it will also protect the body if you tweak it just the right way.
00:09:41.000And besides eating low amounts of protein, the only way to affect that pathway is with a drug called rapamycin, which is a little dangerous to try and is used for immunosuppressants.
00:09:55.000So it's not something that I would recommend, and I don't take it.
00:10:02.000Wow, so this is your daily routine along with what kind of diet do you follow?
00:10:55.000There's a great one, because there's different kinds, and some of them are from the neck down, where they're using liquid nitrogen.
00:11:01.000The other ones, they actually freeze the air, so when they're using the nitrogen to freeze the air, and they're pumping in air that's 240 degrees below zero, and you're going to do about two minutes.
00:11:12.000I do three, because I do it all the time, but it's awesome.
00:11:16.000I do three, and then I take ten minutes off, and then I go back in for another three.
00:12:19.000And we know this because if you create a yeast cell or a worm or a mouse and then you knock out the gene for the sirtuin, now the resveratrol doesn't help the animal anymore.
00:12:29.000That's interesting because when people talk about wine, that's the one thing they say, the resveratrol is an antioxidant.
00:12:35.000Yeah, this is one of those urban myths that never goes away and still fuels a billion-dollar industry.
00:12:39.000But what we're finding is that the molecules in plants, like resveratrol, first of all, we think they're produced by plants because the plants are benefiting from the stress.
00:12:49.000A little bit of stress is good for you.
00:12:51.000What doesn't kill you makes you stronger kind of thing.
00:12:54.000And hormesis was discovered about 60, 70 years ago when people were spraying herbicides on plants, and a little bit of herbicide actually made them stronger.
00:13:03.000And we think that these molecules in plants are similar.
00:13:06.000They make the plant stronger during times of stress.
00:13:08.000So if you stress a grape that's for winemaking, you'll get great wine, but you'll also get a lot of resveratrol.
00:13:16.000And so when we ingest that resveratrol from the plants, we get the same health benefits because the plants are activating their sirtuin pathways and we have the sirtuins and they activate us as well.
00:15:25.000That seems, I mean, for a dummy like me, it seems counterintuitive because what's making you perform better currently, you would think, especially something like amino acids, a natural part of the human body, you would think that that would be beneficial.
00:15:38.000You're adding to your body something that it needs.
00:16:25.000So the idea is you're limiting your calories, you're limiting your carbohydrates, you're limiting your protein, you're limiting your amino acids, but you're ramping up on all these beneficial molecules.
00:16:41.000Right, these pathways that have evolved since the beginning of life to make us live longer during adversity so we can thrive when times come back.
00:16:49.000Do you take into consideration quality of life versus length of life?
00:16:57.000Yeah, well, it's hard to ask the mice how they feel, but we do test them, and we do frailty studies, and we can see that they've got better memory, and they can run further on a treadmill.
00:17:29.000But I'm trying to eat as many vegetables, especially the colored ones, for the reason that I said, which is, well, a few reasons.
00:17:35.000One is that you don't ingest as much protein as you otherwise would.
00:17:39.000You get all the vitamins, but you also get those molecules from the plants that we think make you healthy.
00:17:44.000So resveratrol is just one of a bunch of polyphenols that plants make when they're stressed.
00:17:49.000And when plants are stressed, they go coloured.
00:17:51.000So the purples and the reds and the blues, yeah, those are molecules that are generally healthy.
00:17:57.000And I think, I'm one of the few scientists who thinks this, but I think that we've evolved as animals to sense the plant world.
00:18:04.000And when our food supply is stressed out, then our bodies sense that by when we ingest them, we get these molecules like resveratrol.
00:18:12.000And we've evolved to sense that and we get the benefits of longevity as a side effect.
00:18:19.000So, this is really fascinating to me because the idea that you're trying to balance out the concept of a mouse growing very quickly but dying quickly as well versus something that can extend and live longer and be more vital or have more vitality for a longer period of time.
00:18:43.000Well, so here's the great thing is that now that we believe we've figured out why, not just why, but how this all works, what are the genes and pathways in the body that control this?
00:18:56.000We can, at least in a mouse and probably in a human in a few years' time, and maybe even with these supplements, we'll see.
00:19:02.000We can trick the body into being hungry and being in adversity even if you're eating a lot or you're not exercising.
00:19:11.000And so we're slowly but eventually turning a mouse into more like a human so that even though you can grow and reproduce quickly, you still turn on these protective pathways and live a long time.
00:19:24.000The best example is the nematode worm C. elegans.
00:19:27.000It's been studied a lot for longevity.
00:19:29.000And the mutations that make those worms live sometimes two and up to ten times longer are activating genes that are normally only turned on when they hunker down and turn into a little dour stage, which means that they're not really reproducing,
00:21:40.000Here, myostatin insufficiency produces 15% life extension in mice.
00:21:45.000So those myostatin inhibitors make the mice grow longer.
00:21:48.000So you think that might have had an effect by virtue of the fact that they're more bulky and they have more muscle tissue and they burn off more fat?
00:21:58.000The other thing would be that some muscles are secreting molecules called myokines into the bloodstream.
00:22:04.000And we don't know what they all are, but when you exercise, you do release some of these, and they may also be contributing.
00:22:10.000Because muscles are signaling to the whole body.
00:22:12.000When you go for a run, it's not that your muscles get an exercise.
00:22:15.000Everything in your body gets an exercise by these communication molecules.
00:22:19.000And that's why if you fuse an old mouse to a young mouse, you can have these benefits that the young mouse imparts on the old and actually negatively vice versa.
00:22:27.000And when you say by fuse, you mean by taking the blood of the old mouse and putting it into the young mouse?
00:22:32.000Right, but what we actually do, because that's too hard, you can do it in humans, but in mice what you do is you sew the skin together so that the blood flows between them.
00:22:42.000Yeah, it's not so pleasant, but they don't seem to be too badly affected once they learn how to walk in sync.
00:22:50.000By the way, to all your listeners, we don't do those experiments in my lab, but when I say we, I mean we scientists.
00:22:57.000Yes, the scientific community as a whole.
00:23:01.000What are your thoughts on, if you have any, about the startups that are actually taking the blood of young people and injecting it into the bodies of older folks?
00:23:14.000So I don't think there's a scientific reason to say it won't work.
00:23:17.000And the scientists who are involved are some of my great colleagues, very smart people.
00:23:27.000It's just a little bit out there for me.
00:23:30.000But what they're going to do, what they're doing actually is treating people with neurological disorders.
00:23:35.000A lot of these startups, I'm involved in probably 15 startups right now, What we're trying to do is to treat diseases of aging, and even rare childhood diseases, because you can't treat it aging as a business model.
00:24:59.000I saw an old gentleman yesterday and it was painful just to watch this poor guy walk, you know, hunched over and just struggling to move at an incredibly slow pace.
00:25:09.000That seems like a person with a disease.
00:25:13.000And imagine if we were on a planet now, or an island where everybody lives 300 years, and we'd show up, and you and I in our midlife, we're starting to look old already, and they're going to look at us and say, what is wrong with you guys?
00:27:29.000Because I was having this conversation with someone the other day that as people become more affluent and society becomes more urban, people will have less and less children and the population will stabilize.
00:28:01.000I mean, obviously, most people understand how babies are made.
00:28:05.000Where is the education contributing to a lower population?
00:28:09.000Well, so my understanding is that the first thing you do if you educate young women is that they can make choices for themselves and they're not just subjugated.
00:28:18.000You know, most men would like to have more children.
00:28:40.000And that's going to drag the economy of the planet down, and it's going to be a real problem.
00:28:43.000We're going to waste so much money on keeping older people alive for the last 10, 20 years of their life with dementia, frailty.
00:28:49.000That could be trillions of dollars, just $50 trillion just in this country alone that could be spent on figuring out how to solve global warming, better education, the environment, saving the one-third of species that are becoming threatened.
00:29:04.000That's why I think tackling aging isn't a selfish act.
00:29:07.000It's probably the most generous act that I could give the planet.
00:29:10.000That's an interesting way of looking at it.
00:29:13.000What populations as a whole, when you look at the world, where are the people living the longest and why?
00:30:20.000And they were selling something about their mineral-rich diet.
00:30:27.000Remember they were selling, it was like a big thing for a while, coral calcium, and they were using that as an example of why the Okinawans were living so long.
00:31:13.000Once I'm in it, I just want to keep shoving it in my face.
00:31:16.000But I've done a good job over the last few years of tapering that off, and the intermittent fasting, I think, is probably one of the best things I've ever done.
00:31:23.000In terms of, you know, just maintaining energy levels, maintaining body weight, that kind of stuff.
00:34:31.000For the young audience, compact discs are little things we used to put music on.
00:34:35.000But anyway, these are digital information, of course.
00:34:38.000And the reason we switch to digital in the first place is that it's very copyable and it doesn't wear out.
00:34:44.000Whereas a cassette tape, people our age know that if you try to copy that a thousand times, there's not much left at the end.
00:34:52.000So the compact disk information is the genome.
00:34:56.000The epigenome is the reader of the CD, that little laser that goes around.
00:35:00.000And what I think is causing aging is not the loss of the digital information, but it's the reader, the analog part.
00:35:07.000And that's like a cassette tape that eventually runs out.
00:35:11.000And what's going on really is that your cells are losing the ability to read the right genes the way they did when you were 20. And that's basically noise, informational noise that gathers over time.
00:35:24.000And so what we end up with when we're 80 is a compact disc or DVD that's scratched.
00:35:30.000So the reader cannot read the right genes at the right time.
00:35:35.000Now what we're working on is how do you polish that CD or that DVD to get that information back again?
00:35:41.000And if you could do that, I think that's really the best way to reset your age.
00:35:46.000And we haven't polished it yet, but we're working on ways to actually reset that genome and actually get back the information that we once had when we were 20. So what is happening to the epigenome when you're going through those scanners?
00:35:59.000Well, so what we found is the biggest disruptor of the epigenome is a broken chromosome, a DNA break.
00:36:07.000And I don't know about scanners, that's just an abundance of caution, but an x-ray will damage your DNA, no question.
00:36:14.000Even going out in the sun will do a bit of that.
00:36:16.000And we think that the cell's reaction to that break, having to unwrap the DNA from its chromatin, we call it, and then rewrap it, is what eventually disrupts the ability to read the right gene at the right place.
00:36:30.000So DNA damage is essentially a little scratch on the DVD, and that accumulates over time.
00:36:37.000So being out in the sun does that, but being out in the sun also is beneficial.
00:36:41.000Your body produces more vitamin D... Yeah, well, so there's also a theory called antagonistic pleiotropy, which is what's good for you when you're young comes back to bite you when you're old.
00:36:51.000So you might look good and feel good and get vitamin D when you're young, but the accumulation of these scratches on the epigenome ends up, you know, I'm formerly an Australian, originally an Australian, I'm now American and Australian.
00:37:03.000I grew up in the Australian sun, and I can tell you that, you know, most Australians look older than they should.
00:37:47.000Well, that's one of the first things I noticed when I went to Australia was there's all these sun cancer warnings, skin cancer warnings everywhere.
00:38:20.000But what we're working on is how do you get back that original information into the cell and make a cell not just believe that it's 20 again, but actually be 20. So what do you do?
00:38:33.000There are a set of genes that we and others have found, three main ones, that when you put them into a cell or even into a mouse, they become younger again.
00:43:06.000We've put these reprogramming genes into a virus, which is already used to treat genetic diseases in the eye, and we inject it straight into the mouse's eyeball.
00:43:16.000This sounds like the beginning of a horror movie.
00:43:22.000It's the awesome part that I'm focused on.
00:43:24.000Well, if you're going blind, one injection from your doctor, and then you take an antibiotic to turn the genes on for as long as you need, and you get your eyesight back, that's not horrific at all.
00:43:43.000Yeah, but the crazy stuff, the future is, if this all goes well, you have an injection in your vein, let's say when you're 30, and then those viruses infect your body, and they sit there dormant until you need them.
00:43:59.000You can turn them on with just an antibiotic in a drip or in a pill, or you start to lose your eyesight, take an antibiotic, So you put them in your body almost as an insurance policy and then you have the option to turn them on in the future.
00:44:16.000Now, with every action, we assume there's some negative consequence or potentially negative consequence, right?
00:44:29.000We always assume that, but it's not always right.
00:44:32.000So with the molecules that we've been testing for years now, like NMN, we haven't seen any downside, just longer endurance and protection.
00:44:39.000So there isn't always a downside to these things.
00:44:41.000In fact, if you just think NMN is replacing a molecule that we lose over time as we get older, it's just becoming, you know, it's a fairly natural process.
00:44:49.000No downside exercising and dieting either.
00:45:18.000Get your body damaged enough that it can repair itself but give you the benefits without having a lot of x-rays or radiation overdoing it and scratching that CD. Yeah, that's always my thought on people that do extreme endurance activities like ultramarathons and things along those lines.
00:45:39.000I mean, I marvel at their willpower and their ability to push themselves through that and the physical condition they have to be in to perform such feats.
00:45:49.000But I always think, man, you're probably doing X times the amount of damage to your body that a normal person does at your age.
00:46:18.000Most of us go to the doctor for annual physical, which is ludicrous.
00:46:22.000The idea that your doctor will take hopefully a blood test or prostate exam once a year, that's kind of crazy.
00:46:28.000What happens if you've got a tumor that develops the day you leave the doctor's office?
00:46:33.000So the future, and actually partially for those who are on the cutting edge can be done right now, it's monitoring your body in various ways, genetically, epigenetically, we can measure those scratches right now, and also with blood tests.
00:46:48.000You can also have companies tell you if you're out of range, if you're not optimized, and how to get it back in order.
00:48:23.000So I start at the gym at 2pm on a Sunday, and I'll have a salad wrap or something like that, so I'm not feeling hungry during it, and I won't pass out.
00:49:15.000Well, so once a day of that, or once a week on a Sunday, and during the week, if I have a chance and I'm not traveling, I go to the home gym.
00:49:23.000And when you say you run once a week, is that by design that you only give yourself once a week?
00:49:28.000I probably run two times a week, high intensity, if I could, and I try to do that.
00:49:54.000So I'll sprint and then I'll slow down, sprint, slow down.
00:49:57.000They're actually more difficult than running on a flat surface.
00:50:00.000It's where regular treadmills is actually easier than running because the treadmill's moving and you're just kind of lifting your legs up and keeping moving.
00:50:07.000With this, actually, you're powering it.
00:50:09.000So by you pushing on it, it's actually more...
00:53:46.000Well, I actually had an inflated idea of how bad it was, apparently.
00:53:52.000In talking to another research scientist, he was telling me that the actual amount that they gave to rats when they're diagnosing them with cancer is almost impossible for a person to consume.
00:54:07.000You would have to have ungodly amounts of aspartame in order to get these effects that everyone's terrified of.
00:54:13.000He said the other thing to take into consideration is look around at how many people are drinking Diet Coke.
00:54:18.000He goes, if it was really that bad, they'd be dropping like flies.
00:54:21.000The consideration though is upsetting your gut biome.
00:57:51.000The other thing, as a scientist, what you need is you need to see a thousand different sets of data and put them into one thing and see the connections.
00:58:00.000So I'm exposed to so much information.
00:58:02.000It's drinking from a fire hose every day.
00:58:37.000I haven't, but I've talked to many people that have.
00:58:40.000I've been scheduling it or wanting to schedule it, putting it off for weeks, but I'm going to do that soon because I just know too many people that have extreme benefits from it.
00:59:01.000I've just been more focused on curing aging.
00:59:03.000But NAD does have supposedly some sort of an effect on aging, correct?
00:59:09.000IV NAD? I don't know about IV NAD. It's been poorly studied, actually.
00:59:14.000There's a lot of anecdotes, and I hear about these all the time.
00:59:16.000But I haven't seen really hardcore double-blind placebo-controlled trials.
00:59:22.000Now, NAD in supplemental form though, in terms of orally ingested NAD? So if you give NAD to an animal or a cell, it's taken up really poorly.
00:59:51.000I mean, we're still at the cutting edge of figuring out what's true and what isn't, but NAD is thought to not be well absorbed in the body as compared to these other smaller molecules that the body then turns into NAD once it gets in.
01:02:47.000Yeah, so I said to her, I thought you were one of the world's best dentists, and she said, okay, fine, I'll do it, but don't blame me if it doesn't work.
01:05:57.000So he just had to take his time and really be dedicated and watch his diet, nutrition, and next thing you know, this guy's an elite marathon runner.
01:06:15.000Well, you see that with athletes, like athletes that were fit when they were young and never lost it, really maintained and stayed in the gym and stayed active.
01:06:25.000You see them in their 50s and even their 60s looking great.
01:06:28.000Whereas, you know, it's just once your body deteriorates, it's very difficult to bring it back.
01:06:35.000But if you maintain it, it seems like there's people today that are doing that and it's much more common.
01:06:40.000If you go to a gym, for instance, go to a nice gym, you'll see a lot of folks that are in their 60s and 70s that are really active and they're there all the time and they're regulars at the gym and they look great.
01:07:59.000Like, for you, you get your dad hopped up on all these awesome new drugs, then you get him working on the ethics panel for clinical studies, and then you get him to give you some death row patients so you can try it on, right?
01:08:50.000One of the things that I was talking to my doctor about, he's saying that there are people that just have high blood pressure or higher, you know, higher blood pressure or higher instances of heart disease in their family and it's just a really unfortunate genetic issue.
01:09:08.000But fortunately, we're able to tackle heart disease pretty well these days with blood pressure drugs and cholesterol drugs.
01:09:15.000There are some side effects, no question.
01:09:17.000But what we're talking about with these longevity drugs that are in development is that, sure, you can be prescribed this medicine for your Alzheimer's or for your liver disease.
01:09:25.000But as a side effect, it'll keep the rest of your body healthy as well, protect you against cancer and all these other things.
01:09:31.000That's what's so radical about what we're doing.
01:09:36.000Now, what about CRISPR? And what do you think is going to come out of that in terms of real-world application for an adult?
01:09:46.000If people don't know what CRISPR is, please explain it in layman's terms.
01:09:51.000Yeah, so CRISPR is a term actually was invented in my department partly, so I know it pretty well.
01:09:58.000Bacteria have an immune system that cuts invaders, cuts their DNA. And what we've done now, as scientists, we've now utilized that system, take it out of the bacteria, and we use it to create designer mutations, designer gene changes,
01:10:29.000You can choose exactly where you want to make it.
01:10:32.000And so I think many of your listeners will know that recently, late last year, a Chinese researcher in our field came out and said he's engineered a couple of twin girls with CRISPR to be resistant to HIV, the AIDS virus.
01:11:19.000So the chance of getting HIV in China is one in a thousand.
01:11:22.000So that doctor was seemingly, he thought he was ethical, protecting the babies from something that's, I would say, really rare.
01:11:31.000Whereas if you really wanted to do something helpful to those kids, and we agreed it was something you should do, why not make them resistant to heart disease or to cancer?
01:11:46.000I think because it was a very well understood mutation that would, if you just destroyed the gene, it would work.
01:11:54.000Whereas with these other diseases, you have to be much more precise.
01:11:57.000But the reason that we scientists got really upset was that he did it in secrecy and then just launched it on the world.
01:12:04.000And that kind of thing, because it's a fine line in ethics, you want to be doing that I think he was hoping to win a Nobel Prize or be a star, and it backfired on him because he just did it in secrecy.
01:12:20.000It backfired in the scientific communities?
01:12:24.000In the real world, in the media, I was shocked how little discussion there was.
01:12:28.000If this news came out in the 2000s during the Bush era, there would have been panels, investigations, it would have been in the news for months, but it wasn't.
01:13:34.000Yeah, so I advise governments around the world about what's going on under the radar, as best I know.
01:13:40.000And there are countries, I'm not going to name them, that are doing research under the radar and are preventing people like myself from entering those buildings to have a look at what's going on.
01:13:51.000So I'm sure that what's going on in there is actually a little bit broader than what we hear about.
01:14:00.000But I don't know how long is it before...
01:14:12.000But in countries where there are different standards, what's stopping a mother who wants to prevent their child from having heart disease, which could kill their child, you know, 40% chance versus one in a thousand.
01:14:25.000And eventually, you could make a child that could live 200 years.
01:14:29.000Once we know how to do it, that could be the future.
01:14:33.000There's always a concern that someone is doing something that is beneficial in one way, but negative in another way, and if everyone doesn't get to examine the research, it's very difficult.
01:14:47.000Like, if we in the United States wanted to do something similar to what they're doing over there, we would want to have access to what they've learned, right?
01:15:17.000And what's not really stated, but it's my belief, is that one of the reasons there was such a backlash against this CRISPR designer baby experiment, and it really was an experiment, it's not just that it was potentially dangerous and you could end up with kids that have deformities.
01:15:34.000But also that unless we do this in a measured manner under supervision, there could be a backlash, like there was against stem cell research in the 2000s.
01:16:45.000It's Brian Fogel's documentary on the Russian doping program, state-sponsored doping program in Sochi, the Sochi Olympics, and how they, this incredibly complicated system of stealing the urine and putting it through a hole in the wall and putting fake urine back through.
01:17:06.000Amazing, amazing documentary, but details this incredibly Complicated state-sponsored doping system.
01:17:15.000I would imagine that with something like CRISPR or some various new forms of genetic editing, that that's one of the things that they're going to be looking into.
01:17:28.000That they're going to be looking into things that are going to enhance athletic performance.
01:17:44.000I also write reports for governments, and one of the things that I predicted within the next 15 years was CRISPR being used to engineer the human genome and make a baby.
01:17:55.000I didn't realize it was gonna happen within one year.
01:17:58.000A lot of these technologies that I'm trying to predict happen way faster than even I think are gonna happen.
01:18:04.000Do you think it's possibly happened in other circumstances that they're not going public with?
01:20:41.000If your dog has got a kidney defect and it's only going to probably live to be nine, meanwhile, that dog's going to live to be a thousand years old.
01:21:07.000Like if your dog, like right now you're talking about on the podcast and a bunch of people are probably going to remember, but a lot of people forget.
01:21:14.000But if like 15, 20 years from now your dog's still chasing balls and people are going to come over your house, hey Dave, what the fuck's going on with your dog, man?
01:24:23.000Well, I mean, especially if you drink them in the juice form.
01:24:25.000I know a lot of friends who really enjoy fruit juices and vegetable juices, and I always say, well, I mean, vegetable juice, yeah, it's probably great, but fruit juice, man.
01:24:35.000Drinking a big glass of orange juice, you might as well be having a Coca-Cola.
01:24:40.000So our household has a ban on smoothies and fruit juices and sodas that have sugar in them.
01:24:49.000God, I used to be able to go to Jamba Juice and get one of those big old smoothies and feel like you're doing something good for your body.
01:24:56.000I used to think, yeah, look it, I got all this blueberries in there and great stuff.
01:25:00.000But meanwhile, there's just a gang of sugar in that thing.
01:27:10.000The one thing that worries me about children that are overweight skipping a meal, though, is that they're not as disciplined and they're not so good psychologically with struggling and having hunger pangs and that you're going to fuck their head up.
01:27:51.000I think that it's probably far better to adjust their diet.
01:27:55.000And if you've got a kid, just slowly get their body weight down with exercise, particularly with resistance training and doing things that really burn off a lot of calories and then just get them off the sugar.
01:28:08.000And then I think the weight will slowly slip off, probably not even so slowly if you can really get them off a significant sugar binge.
01:29:49.000I just have to make sure it's nothing that's confidential.
01:29:53.000But there's a lot of interesting stuff going on on the planet.
01:29:56.000There's areas of biodefence that are pretty scary.
01:29:59.000So some nations are apparently working on using CRISPR and other gene editing systems and modifying bugs that could wipe out a few hundred million people pretty quickly.
01:30:34.000So the Navy SEALs came up to my lab, and they'd like to ask our group to solve some hard problems.
01:30:40.000And so the problem they set us on was, how do you kill anthrax safely?
01:30:47.000Now right now it's very difficult to kill, of course.
01:30:49.000When the anthrax letter was opened in the Senate, what was it, a number of years ago, It cost $25 million.
01:30:54.000They had to seal it off and put hydrogen peroxide all over everything, destroy the computers.
01:30:59.000So they're wondering, how do you kill anthrax safely so that you don't have to be in a hazmat suit to do it?
01:31:05.000And so what we came up with after thinking about it for about a week was we need a biological solution, not a chemical solution.
01:31:14.000And so we found an organism, its whereabouts I cannot disclose, but it's a very interesting organism that grows at high temperature, and it destroys all bacterial and viral life.
01:31:28.000And it wipes it out, and it doesn't hurt humans at all.
01:31:32.000Or at least in animal studies, you can breathe it in, you can put it anywhere, and it's fine.
01:31:36.000So this is a cocktail of enzymes that destroys the microbes, including anthrax.
01:31:44.000So it doesn't have any effect on humans, but what about the bacteria that lives in our body?
01:31:52.000What we're hoping to do is to do a clinical trial soon on removing biofilms.
01:31:57.000So in the wounds of patients, the problem, the reason they don't heal very well, especially these diabetic chronic wounds, that, by the way, every 10 minutes someone's losing a limb thanks to that, These biofilms, you have to digest them off.
01:32:10.000And do you know how they do it right now?
01:32:14.000Then they cut the skin and they keep cutting and they're cutting and eventually you lose a limb.
01:32:19.000This looks really promising in animal studies that we should be able to not just kill the bacteria in the wound, which is a problem, but get rid of that biofilm.
01:34:27.000It got into her brain and the hospital wouldn't give her the antibiotic because the tests weren't quick enough and they wouldn't give her the antibiotic until the tests were positive for insurance reasons.
01:34:37.000And I said, just give me the DNA of my daughter, the spinal fluid.
01:35:02.000But he did a famous person's genome recently.
01:35:05.000He's been trained on mummies, and he did Kennewick Man.
01:35:10.000So this technology can be teamed up with what I've done to be able to get rid of all the human DNA out of a blood sample, leave the viruses, leave the bacteria, and then run that through a supercomputer, all the DNA, and tell you within probably seconds,
01:35:37.000There are so many people that are infected with it, and I know personally maybe 10 people that have it, and a couple that have had significant issues with it that have lasted for years.
01:35:48.000I know a guy who was hospitalized for a full year on it.
01:35:51.000It's really bad, and it can hide as well.
01:39:22.000What can be done to somehow or another eradicate those things?
01:39:27.000Oh, so again, one of my friends, got a few friends here, she was working at MIT and she's developed a way using the CRISPR system to kill these, as you say, damn little fuckers.
01:39:39.000And so there is possibly going to be the first test of releasing a modified organism, the Lyme organism, to kill them off.
01:39:53.000It's going to be like that Brad Pitt movie, the zombie one, World War Z. Might be, but on the other hand, we might all be saved from Lyme disease.
01:40:38.000And now there's the, I'm sure you're aware of the Lone Star tick that gives people that alpha-gal disease, the one that makes you allergic to red meat.
01:40:54.000It's crazy to see these things morphing.
01:40:56.000Well, they're morphing, and there are a lot of bugs we don't know.
01:40:59.000Somebody just published a few days ago that they took surveys of the microbiome on the skin, mouth, gut, across the planet, different races, different foods, geography, and they have 100,000 different organisms living on humanity.
01:41:43.000But these wounds, they're actually, if you want to kill the bacteria in a wound, they're different in the wounds of people in India than they are over here in the US. Oh wow, that's interesting.
01:41:53.000And obviously they have different diets too, so there's probably different things they're used to consuming, and so their gut bacteria is different.
01:42:59.000But who tracks their time now anymore?
01:43:01.000But I would think that with a guy like you who's so – you concentrate so much, you're so focused on anti-aging that having a gigantic workload would seem to me to be – that would be an issue in terms of like overtaxing your system,
01:44:24.000The reason that I look after myself as best I can when I've got the energy is it would be a bad look if I died from heart disease tomorrow.
01:45:17.000How far away do you think we are from doing something like that?
01:45:20.000Well, it often comes as a shock to people who don't work on this that we're already testing these molecules in clinical trials on elderly people.
01:45:28.000I've been doing that for a number of years now with some positive results.
01:45:33.000Over at Harvard, we were giving NMN and another molecule called MITB626. What's the other one called?
01:47:30.000We've figured out that the lining of the blood vessels needs NAD as you get older.
01:47:34.000Well, they need it all the time, but as you get older, you don't have enough NAD. So the NMN replenishes that and allows the blood vessel lining to respond to exercise and even grow blood vessels if you don't exercise.
01:47:47.000And so those mice, they ran and ran and ran.
01:47:49.000They didn't get lactate buildup as much.
01:48:04.000We even pinched off an artery and the body responded much better to restoring blood flow, which would be great for patients who have a heart attack.
01:48:15.000Now, with human beings, what has been the most dramatic result?
01:48:24.000That's a hard question, because a lot of it's early stage.
01:48:29.000We developed a molecule that seemed to effectively treat a disease called psoriasis, which is the inflammation...
01:48:48.000So it's an activator of one of these sirtuins that we found in yeast originally, these sirtuin protective enzymes in the body, and they're anti-inflammatory, and so it worked well against that disease.
01:49:00.000So psoriasis has something to do with inflammation?
01:49:55.000Is there anything promising results on humans other than NMN? Yes, there are.
01:50:00.000So this mTOR I mentioned earlier where the drug rapamycin, which is too dangerous to try on normal people, that drug has been tried on elderly people and it boosted their immune system in the same way that you see with calorie-restricted mice.
01:50:15.000And so that was an early signal that you might be able to reverse aspects of aging in the elderly with that drug.
01:50:20.000Now, with older folks, one thing you see is the body doesn't produce collagen as much, your skin gets lax and starts to sag.
01:50:32.000What things could be done to mitigate that?
01:53:29.000We're about to announce, maybe there's a sneak preview for everybody, an academy for aging research of the top, I think, 20 scientists in the world are banding together to produce white papers and opinions.
01:53:45.000But yeah, we call it longevity research.
01:53:48.000And so anti-aging is more the Botox and that kind of stuff that we don't want anything to do with.
01:55:27.000But I think one of the most important questions they'd ask to tell if we were an advanced nation or advanced species is, have you figured out aging yet?
01:55:45.000And they're like, come back in a thousand years.
01:55:48.000Well, I mean, how many people do you think worldwide are working in your field?
01:55:54.000So in terms of leading labs, there's about 20, 30. Broadly, there's probably a few hundred labs.
01:56:02.000And are they all in essentially the same field of study?
01:56:04.000They're all working with the same molecules and the same parameters?
01:56:10.000No, not everyone works with molecules, but what I can tell you is we get together in conferences and we talk about discovering a new gene that extends lifespan and a new molecule that's working in mice or sometimes in humans.
01:56:47.000So I came to the US from Sydney in 1995, went to MIT, and the scientists in the lab that I joined, Lenny Garanti's lab, two students had just started working to figure out why yeast get old.
01:57:01.000And I joined as the third senior person to join.
01:57:04.000And all the other people in the lab, there were about 18, 19 people, they said, You are nuts.
01:58:31.000And also, and this may be true in Hollywood, in science, if you come up with a new idea and you're young, you're a young Turk, and you're upsetting the status quo.
01:58:40.000Thomas Kuhn's book on the structure of scientific revolutions just had it right.
01:58:46.000About chemistry and physics, but it applies to biology.
01:58:48.000If you come up with a new theory that's that disruptive, the current leaders will attack you, and it's a period of chaos, and you just have to get through it.
01:58:57.000And fortunately, I'd read Kuhn's book, and I knew that this was normal.
01:59:00.000But a lot of people around me were saying, oh no, people are saying we're wrong, and it's controversial.
01:59:13.000Do you think that's because the people who are the old guard are upset they didn't find it themselves, or are they upset that your new findings will make their work look irrelevant?
01:59:24.000Yes, it's probably a bit of both, but mostly it's that they're worried that their lives will have been in vain if what they're working on is not true.
01:59:33.000Yeah, there's an amazing documentary on the Sphinx where these geologists are talking about some of the water erosion outside the area of the Sphinx, and they're saying this points to the fact that construction was thousands of years older than they thought.
01:59:48.000And you see this one Egyptologist freaking out.
01:59:53.000What evidence of this culture are you talking about?
01:59:55.000Because apparently it would have predated the known dates of 2500 BC, would have made it like 7000 years older than that.
02:00:05.000Because it would have to be back when there was rainfall in the Nile Valley.
02:00:08.000And you could see this guy's ego kicking in because he was a professor.
02:00:12.000He had been teaching Egyptology and he was freaking out.
02:00:15.000Instead of examining this evidence like, whoa, like talking to this geologist who studies rocks and erosion, who is really steadfast, he's a Boston University geologist, Dr. Robert Schock.
02:00:27.000And he's saying, this is evidence of water erosion.
02:01:20.000See, the problem with how biology and actually most facts are taught or theories are taught is that there's a textbook and that's the Bible equivalent.
02:01:30.000What I try to teach my students is, can you please just forget everything you've just learned?
02:01:35.000And what's important to know is that most things we think we know are not correct.
02:01:42.000Newton was wrong, but he helped us get here.
02:01:45.000Expect that we only know 0.01% of what we need to figure out, and a lot of what we think we know is wrong anyway.
02:01:53.000So even if you have the greatest theory, expect that it will be overturned, but you can at least cherish the fact that you've helped us get to that point, because without Newton we wouldn't have quantum physics.
02:02:03.000Well, for someone like me, hearing you say that, it's very promising.
02:02:28.000When I found out that scientists would...
02:02:31.000Would ignore information or use their own personal biases against information or attack research because it somehow negates what they've done.
02:02:41.000It's very disheartening for someone who's not a scientist.
02:02:44.000You go, oh no, the ego's in science too?
02:02:47.000It's disheartening as a scientist, I can tell you.
02:02:50.000There was a time of great change in the aging field where we discovered genes control aging and molecules like resveratrol could extend health and lifespan.
02:03:29.000That must have been a tough time, though, for you as a young man, and, you know, you're hearing this from these established scientists, and part of you must have been, like, thinking, like, geez, are they right?
02:03:45.000But you go back to the lab and you retest it.
02:03:47.000So I went through a really brutal period in my career where we had data, we interpreted it, we published it in the top journals, and it was about how resveratrol works on that sirtuin enzyme that I mentioned.
02:04:19.000And it took another, I think, four years to get to the bottom of it, but it turns out in the end I was right.
02:04:25.000But there were days when I said, screw humanity, I can't even be bothered getting out of bed if this is how I'm going to be treated for trying to devote my life to the betterment of people's lives.
02:04:36.000I think anybody who's in a position in their career like that has to have gone through really hard times.
02:04:43.000It's just discouraging from a non-scientist who relies on people like you.
02:04:48.000For someone like me, who relies on the folks like you out there doing the hard work, that you would face that sort of, I mean, I guess the best way to describe it would be ignorance.
02:05:01.000Well, it's okay for scientists to challenge a theory.
02:05:03.000That's what I did and what everybody is trained to do.
02:05:06.000But to do it in such a public and controversial – it was vicious.
02:06:29.000The early data was that we could mutate or change the enzyme so that it wasn't going to be activated by resveratrol, and we found that mutation.
02:06:40.000Now that just technically, or non-technically, technically means that we could change the enzyme in a way that wouldn't work.
02:06:48.000So we then put that non-working enzyme into a cell, and now we have a mouse that doesn't work, and we give it resveratrol.
02:07:04.000But the real change was that there was a company that I started that was making drugs, the one that cured, or at least seemed to cure psoriasis.
02:07:15.000And they had made these very synthetic molecules that were not related to the plant molecule resveratrol.
02:07:22.000And so I said to myself and to the student who was working on it, the very brave student, If the change in that enzyme also blocks the drug, then we're on to something.
02:07:33.000Because that means two separate groups working on separate types of molecules, different people, different systems, all get blocked by this one little change in the enzyme, then we're right.
02:07:46.000And so he walked over to the company, got the molecule, threw it on the enzyme, and it didn't work on the mutant.
02:07:52.000And that was me rejoicing because I could say there is a universal activation mechanism on this one enzyme.
02:08:05.000And now there's an interesting thing that just came out from Spain that metformin, the diabetes drug, may actually work the same way as these other molecules by activating our favorite enzyme, the sirtuin.
02:08:28.000It gets so bad because you've got this tight-knit group of scientists and you have lab meetings and you present your results and usually you're very supportive, trying to help.
02:08:36.000I had one guy saying to my student, David doesn't know what he's talking about.
02:09:09.000In science, because it's very collaborative, and often your enemies are reviewing your own work, if you build up too many enemies, you won't survive.
02:09:19.000No, it's definitely a healthier approach.
02:09:21.000I probably would do exactly what you did.
02:09:23.000But still, it's got to be beautiful to come out on the other end and be proven correct and actually be at the forefront of these emerging technologies.
02:09:34.000I don't mean to rest on any laurels, but the What I do is I pause and I remember how hard it was to get here and how fortunate I am to have made it this far.
02:09:43.000And I'm working with hundreds of collaborators around the world to make this come true, this idea that we can really treat aging and prevent deterioration.
02:10:22.000I think I mentioned to you that I've started a few companies.
02:10:26.000What I'm trying to build are companies that are the 21st century version of a pharma company that actually has a decent reputation in the world.
02:10:35.000I think it's pharmaceutical companies, whether it's deserved or not, have a pretty bad rap.
02:10:39.000I'm trying not to fall into that trap, but I'm also trying to use 21st century technology to not become too bureaucratic as well within the organization.
02:10:49.000You were also talking, I don't know if you could talk about this, before the podcast about How you have to make sure you have zero conflicts of interest.
02:11:01.000I don't endorse anything, no products.
02:11:04.000But if you look on the internet, if you Google David Sinclair and NAD or aging, you'll see that people put my name and my face all the time on their websites and I get questions every day.
02:11:13.000Every morning I wake up, which product are you endorsing?
02:11:33.000And I also want to be able to have opinions on these molecules without someone accusing me of doing it for a profit.
02:11:39.000That's what I would think would be correct, because if anybody could point to that and say, hey, he endorses this because he's making money.
02:11:48.000That's what would be, yeah, that would be the thing that, I mean, especially because most people aren't going to do real research and develop the nuanced understanding of your work and what you're doing and what it means and how long you've been studying it.
02:12:00.000They go, oh, he's doing it because he's making money.
02:12:04.000Well, you know, I've made a fair amount of money in my life.
02:12:06.000My first company, even though I wasn't the major shareholder, was sold north of $720 million.
02:12:12.000So that money I'm not immune to, but I do reinvest almost all of it.
02:12:18.000Actually, all of it, my wife will tell you, into new ventures to change the world.
02:12:23.000So the Lyme disease company and the MIB 626 company, Metro, these are funded initially by me.
02:12:30.000Now the conflict arises because I'm studying these molecules in the lab and I'm on the board of directors and advising these companies as chairman, vice-chairman.
02:12:38.000The only way around that as a scientist that we have as our defence is we disclose everything.
02:12:44.000So initially I would disclose it to the government and to Harvard.
02:12:55.000If you go to my lab's website, you'll see everything that I do.
02:12:59.000And hopefully that's protection from being accused of being biased.
02:13:05.000But what I definitely do in my lab is I say to the students, if you get a whiff that I'm doing anything biased, I wouldn't do anything consciously, but maybe there's some unconscious bias.
02:13:19.000But I've been doing this for 25 years.
02:13:21.000I think I'm pretty good at putting a wall between the two.
02:13:28.000And the other thing that I want everybody to know is, in the lab we do very basic research.
02:13:32.000We try to understand the fundamental reasons why we age and how to reverse it.
02:13:36.000The companies are more worried about how we're going to do a clinical trial, which is a very different world, so they don't overlap much.
02:13:42.000Now when you want to bring something to the market or you want to try something on people, what's the process?
02:13:49.000Like say if you have some sort of a molecule that you want to try out on people, what is that process?
02:13:57.000So it's a few years of often making a better molecule, but let's say you've done that work.
02:14:03.000Now you spend a year testing it on at least two different species, usually a rodent, a mouse, and a dog.
02:14:12.000But you try to do everything you can before that to make sure it's not going to be unsafe, testing it on cells and other things that are not living, or at least don't feel anything.
02:14:22.000But the FDA, Food and Drug Administration of the U.S., requires if you're going to make a drug, you have to test it on at least two different species.
02:15:31.000If we're successful at having a drug that treats aging, we'll treat a disease like diabetes first, but then it could become the best-selling drug of all time if it's proven safe.
02:15:44.000Who wouldn't want To have a drug that could protect them from all these major diseases.
02:15:49.000Yeah, but how much would something like that?
02:15:51.000You'd have to sell it for so much money to make up for all the research money, right?
02:16:18.000And so that's a very different approach and that's one of the reasons that I've, in large part, used my own money to do these things so I can have that say and do what's right for the planet.
02:16:26.000So when you do do that, how will you decide how much something costs?
02:16:31.000Based on the ability to just maintain the company?
02:17:02.000Because pharmaceutical drug companies are always thought as being a devil.
02:17:05.000Meanwhile, they're responsible for so many things to keep people alive as well.
02:17:09.000But because of the fact they're connected to things like OxyContin and Fentanyl and things that kill people, and it's been proven that there are certain unscrupulous drug companies that have pushed things out there that they know have negative effects because they knew they could profit from it.
02:18:10.000Yeah, and so we just recruited to one of the boards of the company someone from a consumer company, which is a strange choice, right?
02:18:17.000But this is a person who's done right at that company for the world, a company that used to make just some consumer products that weren't healthy, and he turned that around.
02:18:29.000And that's the kind of person I want to work with who cares about the planet more than they care about the ultimate profit.
02:19:49.000You can merge that data with the inside tracker data and have this ultimate personal angel for health that will hopefully one day be on all of us that we've got a personal tracking device.
02:20:02.000It'll tell us if there's something going wrong.
02:20:04.000If you got a cancer cell detected, go get that eliminated.
02:20:06.000It's crazy these days we have to wait till there's actually a tumor that's making you sick before you actually go to the doctor.