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Welcome everyone, this is Dr. Mercola helping you take control of your health
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and I am just absolutely delighted to connect with Dr. David Sinclair who is a
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professor of genetics at Harvard Medical School and generally recognized as one
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of the major thought leaders in the science of how to improve our not only
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our lifespan but our health span. So he started in Sydney, got his PhD there and
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then he went over to Lundy-Garanti's lab at MIT and then went to his got his own
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lab at Harvard Medical School in 1999. He's been working there ever since and
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really come up with this astounding discoveries which we're going to talk
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about today but that one of the primary focuses is his new book which is called
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Lifespan, the revolutionary science of why we age and why we don't have to do
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that. And it's going to be available September 10th and if you're
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watching this it's not September 10th you can pre-order it on Amazon. So
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welcome and thank you for joining us today. Thank you, it's great to be here.
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Yeah, yeah so you talk about a lot of great things in there and I want to
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really highlight some of the concepts that you discussed because I think
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there's so much potential to help us and hit this really the the king of all
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diseases which is aging. So you talk about calorie restriction as being the
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only proven non-pharmacological method of consistently extending lifespan and
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protecting against many of the age-related diseases. And what so you and
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then you also discuss intermittent fasting. So I'm wondering if the one of
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the benefits of not eating is suppressing mTOR and activating
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autophagy. So I'm wondering what type of conclusions you've reached with respect
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to the optimal timing of the periods of the time-restricted eating and the
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frequency of that and how you think integrating fasting or partial fasting
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into that series might look like. Yeah, well we've known for probably more than
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now 5,000 years that being a bit hungry is good for you. So this is not
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revolutionary. What's been more revolutionary in the last few years is
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the discovery of biochemical pathways that actually seem to underlie this
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actual protection against disease and aging itself. And so we're not so much
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guessing anymore what's going on and science has gotten involved and we're
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doing more and more studies certainly in humans but also in animals to see what
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best diet works. And the bottom line, I get questions every day I wake up to
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probably a couple of dozen emails about this topic. Nobody actually knows what's
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best but we can go through them and I can talk about which is my favorite as
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well because there's it's not just a science aspect it's also social. We love to
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eat, we have traditions, we have typically three meals a day and trying to deviate
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from that is really quite challenging. Calorie restriction in animals and in
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humans is about 20 to 30 percent less than what a doctor or a veterinarian
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would recommend. I also struggled with that one so I certainly wouldn't
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recommend it. It really means you've got to be hungry for most of the time
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and I'm sure you get used to it but I didn't get that far. After about a
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week I got too hungry and I gave up. And then I didn't restrict my diet for many
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years actually. I had kids and that's really hard to do. But more recently what
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I've done which I find very easy to do is basically miss a meal once a day and
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I'm not hungry in the morning some people are not hungry at night. If you
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can go for say it's seven o'clock at night all the way through to lunchtime
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based on the animal studies that I've seen published and some in my lab that's
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very likely to do you a lot of good in the long run and in the short run. And
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the science behind it's really interesting I'll come back to that but
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there are other diets that other people have found to be effective in
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terms of improving biology and biochemical markers. One is the 5 plus 2
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diet. Michael Moseley. Exactly I'm sure many of your viewers are familiar with
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that one. That one is also quite doable especially if you have sodas
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and things like that that can actually help just bubble the water. More extreme are
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those diets where you go for a whole week every couple of months or every few
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months. I haven't tried that I'd like to. My view on that is that
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that's probably going to work the best if you can do it because it doesn't just
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trigger the short-term pathways that we've been studying in my lab. But a week
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of fasting will really start the body to start consuming its own protein and this
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is as you mentioned autophagy that's what autophagy is it's the consuming of
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our own biological material which is typically protein. And actually talking
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with people who have done these fasting regimens after about three days
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something different starts to kick in and people who try this tell me that
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they have a feeling of euphoria and they definitely get an added boost. But
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just let me quickly go back to why we think this works. So we've been studying
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in my lab for the last 20 years genes that respond to diet but fat to fasting
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and calorie restriction and the upshot of it is that our bodies respond to
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adversity or perceived adversity. They turn on these defensive pathways it
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changes a bunch of genes that switch on to defend our bodies. And at
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least from many different animals things as small as worms and flies all the way
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up to mice and rats these defenses of the body are extremely good at protecting
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us against diseases from diabetes to cancer heart disease even dementia
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Alzheimer's. These are things that modern medicine has struggled to combat and
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this seems to be the very simple way to get the body to fight against those
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diseases. Often I'm asked how early should you start? In the animal studies
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and in rat studies, mouse studies, the sooner you start the better and the
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longer you do this the better in your life. Clearly we don't want to be
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recommending or seeing teenagers or even people who are in their early 20s do
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this because there's still a lot going on in their bodies and their brains. But
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after 30 if you extrapolate from the animal studies then the longer you do
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this in the lifespan the better. I'm just turning 50 now and I wish I had
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started earlier. Yeah me too. So you mentioned stopping eating at 7 and
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there's a large number of people who advocate restrict not so much
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necessarily tying it to a specific time but at least three to four hours before
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you go to bed. I've been largely as a result of your exposure to your videos
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was been fascinated by the NAD and his family, his cousins like NADPH. When I
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started studying NADPH I realized that the biggest consumer of NADPH which is
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a molecule that essentially is a battery cell and recharges your
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antioxidants is fatty acid synthesis. So if you're eating shortly before you go
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to bed that energy can't be consumed and it must be stored as fat and that's
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going to really lower your NADPH levels which is not a good thing to do at night.
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So I'm wondering if you have any thoughts on that timing of the last meal.
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Yeah I do and I wish I could take some of my own advice and medicine. I think
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if you can have a light meal at dinner a typical European dinner. My wife's German
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she likes to eat small meals. That's great. I tend to snack at night so it's
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my downfall but yeah to be able to have that fast overnight that'll boost your
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energy levels up and NADPH as well. These are all good things they turn on the
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enzymes that we study called the sirtuins. They need NAD to function and
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you can use the whole night to ostensibly repair your body and protect
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it from what happens during the day. I also I try to take a couple of
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metformin pills for two reasons. One is that my family has a history of diabetes
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and metformin is very effective at treating diabetes and even preventing it.
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So I do that for disease reasons but also because the work of many labs has
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pointed to not just animals but tens of thousands of people in clinical trials
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benefiting from that drug which seems to enhance and mimic the benefits of
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fasting. So you talk in your book about this concept of antagonistic
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pleiotropy which is essentially multiple actions some of which may be
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counter to the intended consequence of the intervention. So with metformin you
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describe the benefits which is why you're taking it but you know there are
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some studies published that show that it's a pretty potent mitochondrial
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poison and that it really targets mitochondrial complex one and shuts it
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it radically inhibits it so that you end result is you're producing a lot less
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ATP. So yes it up regulates the APK but in your evaluation of the literature how do
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you reconcile those two? Yeah so here's how I take the literature and there's
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hundreds of probably even more thousands of papers that I've read on this topic.
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Here's my summary but you know I'm a PhD and this is one man's opinion but what I
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take away from it is that short-term exposure to metformin high doses yes it
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will inhibit complex one and lower ATP. That's also true for as veritrol by the
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way. What was in burperine too. Yeah right but it I regard it as hormesis a little
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bit of what doesn't kill you actually makes you stronger and so the body
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recognizing that there's low ATP levels and higher AMP levels will stimulate AMP
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which is known to be beneficial and will actually compensate by revving up the
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mitochondria and building more mitochondria in various organs
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particularly the muscle of your body and so you know a little bit of inhibition
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leads to a kickback and a compensation so that's why I think that actually
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metformin is beneficial even though it starts out as a as long as you don't
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overdose it a relatively mild mitochondrial inhibitor and you know
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that in the history of humanity and in animal studies there's a long literature
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of molecules that if you give a lot of high dose acutely it can actually kill
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you but little doses as long as they don't do harm can have a positive effect
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in the long run and you know this the same is true for fasting if you don't
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eat we know what happens you'll starve to death you trick the body into
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thinking times are tough without leaving a long lasting that any damage and the
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body actually does better in the long run. Okay let's get into a really
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important part of your book which is the balance between anabolism or the
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building of muscle tissue and catabolism which is the tearing down and repair and
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regenerate and repair of it so interestingly when you fast growth
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hormone levels increase and maybe you can go into that because it's it's kind
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of is somewhat counterintuitive because there's no nutrients available so why
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would you think growth hormone would increase so maybe you can discuss that a
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little bit in the in the influence on IGF-1. Right so so IGF-1 is something like
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growth hormone and and growth hormone itself also in the short run don't seem
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to be healthy at least in animal studies and also Nir Barzilai for Albert Einstein
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College of Medicine has studied long-lived families centenarian families
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and what he's found in particular to IGF-1 is that some families actually can
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have high levels of IGF-1 but still live a long time and the reason for that is
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that they they don't have the IGF-1 receptor that's as active. Is that
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Laron syndrome? That's I understand that's the growth hormone as well so
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it's similar no he's a he's a Ashkenazi Jewish family that has 100
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hundred year olds but it's a similar concept is that if you're not responding
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to these hormones it doesn't matter really how much the body produces you
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still have an effect that mimics essentially the benefits you want. It's
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interesting actually that the growth hormone is stimulated by fasting there
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must be something and I'm unaware of exactly why but we know that that
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fasting doesn't lead to bigger animals it's actually the opposite so it could
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be that and now I'm just speculating but I think it's worth discussing and
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thinking about that these short-term bursts of hormones may help the body
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recover from injury but those little spikes don't last long so that you're
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not having any downside. The other thing about growth hormone and I know a lot of
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people including viewers of this show will be wondering what about growth
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hormone is it dangerous in the long run should I be taking it should I not? Now
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now I haven't seen any evidence that growth hormone is going to make you live
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longer typically it's the other way around that people who have a lack of
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growth hormone activity live longer. The rotten dwarfs tend to have this disease
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but in the short run if you need to repair your body and build up new muscle
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which of course prevents falls and accidents in the elderly you know I'm
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perfectly willing to entertain the possibility that that building up body
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bulk and testosterone is the same will prevent these accidents that actually
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largely are a problem for longevity there's a saying actually that the the
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way to longevity the best way longevity is to hang on to the handrail and so
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it's real trade-off it's a trade-off you know that if I was to summarize
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everything that I've learned over the last 30 years it's everything in
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moderation and and nothing don't do anything too consistently because it's
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like a frog in a hot water bath or in a fry pan your body needs to be primed and
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then allowed to relax and challenged and then allowed to relax and so these diets
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and these growth hormone spikes I think they're good you just don't want them on
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all the time because then your body doesn't have a chance to recover and you
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don't get long-term benefits okay so tangenting off the elevation growth
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hormone during a time-restricted eating fast of 16 18 hours or even a longer
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fast many people believe that the optimal time to engage in resistance or
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strength training might be right before you have your first meal so that you're
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still fasting your growth hormone levels are activated and you'll get maximum
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benefit from the anabolic stress of the exercise which of course is increasing
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PGC 1 alpha mitochondrial biogenesis and a lot of other benefits that occur
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during exercise so anybody caught any yeah yeah this is really good you're
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talking about the cutting edge of thinking so people who are discussing
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that idea I think are similar similar to the way I'm thinking about biology you
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know again in the full disclaimer this is now we're discussing the cutting edge
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of science so we don't know fully the answers to this what makes sense to me is
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that we don't want too much protein in our lives we don't want to eat a steak
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every meal because what we've learned through the work of David Sabatini and
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many others in the field Matt Kaeberlein that at least in animals and it looks
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like in people as well that inhibiting the mTOR pathway by having a lack of
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amino acids certain amino acids is healthy and does actually lengthen
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lifespan in animals but does that mean that you shouldn't eat protein absolutely
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not there are times when eating protein is important same for probably
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testosterone same for a growth hormone and then but now we're getting into the
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nitty-gritty is if you are pulsing these things when do you do them together and
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when you do them apart and to me and what you know let me talk about what I
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do personally because that's that's actually a better way to approach the
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discussion if I'm going to have a steak I try to be vegetarian but let's say
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I'm gonna have a protein shake I'm gonna do that just before just after I've
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exercised but then I'm gonna also have a period in the week where I don't have a
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lot of protein and I might just have some salads and that's where I get my
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protein so my body is going like this but it's not out of sync at times when
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my body needs protein or for instance needs growth hormone so I think what
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you're what you're saying is is really going to be the future that we can't
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just say doing one thing constantly is the right thing to do and we have to
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time these beautifully otherwise we're causing stress and damage but then
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preventing the healing process by doing something else yeah well thanks I do
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agree with you I think this is the cutting edge and a really an important
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question that many of us are challenged with and especially in the fact that
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you so well bring out in your book is we age you get beyond 65 our protein
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requirements actually increase for a variety of reasons from about 1 to 1.2
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grams per kilogram and so the key is to cycle the suppression of autophagy by
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not activating mTOR and not giving these calories in protein because protein
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especially animal protein and branched chain amino acids will activate mTOR
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almost universally but I'm I can just share my example I wonder what your
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thoughts are on it because I have an 18 hour time restricted eating window that
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I don't eat and once a week I'll extend that to 42 hours so I'll take a day off
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so I do you think that that regular daily eating window of six hours
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combined with a weekly one day full fast is enough to activate autophagy and
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suppress mTOR and not get the downsides of continuous mTOR activation yeah it
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doesn't it doesn't make sense to me people haven't even done this in animal
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studies yet people need to do that but scientifically it makes sense to me that
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being hungry a little part of the day will will activate turn on NAD you'll
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get it in mTOR inhibition and amputinase will come on but probably the way I'm
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doing it which is not as diligent as you Joe I'm only doing this kind of a level
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of reset and I think it's good but it's not perfect what we really want to do is
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this and then BAM really get a big reset and start showing up the the
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misfolded proteins get the autophagy going get the sirtuins to go repair
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everything in the cell that they possibly could and so I think that's
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right that a little bit of stress every day and a lot of stress once in a while
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is a great combo but I think that that would be something to actually study I
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might have any I haven't seen these studies on it either I'm hoping someone
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this process of doing those who's really like the answers but and I guess
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there's the where the technology is advancing where we'll soon be able to
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measure metabolites more easily than in the research lab and by doing so get an
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indication of what might be the best strategy now in your book I was so happy
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when you started discussing lysine which is the shortest amino acid that we have
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and it's a very important one and it actually I think it may be the most
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common I think it's about 11 11 to 12 percent of the total amino acid content
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in the body and most of us I mean you didn't glycine ingest and didn't used to
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be an issue because we ate connective tissue and glycine is loaded in collagen
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so third of the proteins in collagen and connective tissue are glycine so it
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didn't used to be an issue but we're not eating connective tissue much anymore so
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unless you're consuming bone broth or collagen supplements you're not getting
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it so why don't you talk about the importance of glycine especially with
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fructose consumption that's so rampant in the United States and the advantage
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of doing it especially with the glycine the thionine ratio well so the reason
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that I take glycine actually specifically trimethyl glycine is is
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actually to counter what I think might be going on with an NAD booster I'm
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certainly not an expert in glycine other than that but I can talk about the
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trimethyl glycine component if you'd like sure yeah so this is a big question
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in my field so just to take a step back my field and a lot of what my book is
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about is being able to trick the body into being hungry and having exercise
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| 00:22:23
|
and one of the molecules that does that is NAD NAD stands for nicotinamide
|
| 00:22:30
|
adenine dinucleotide and we have it in our body as we exercise that we get
|
| 00:22:34
|
hungry it goes up as we get older it goes down and it's needed for life it's
|
| 00:22:38
|
also needed for turning on these defensive enzymes that we work on
|
| 00:22:41
|
concert to us now to raise in a d levels what we've done in my lab to mice for
|
| 00:22:47
|
the last decade is we give them precursors to NAD so we give them
|
| 00:22:51
|
molecules like nicotinamide riboside or NR or nicotinamide mononucleotide also
|
| 00:22:58
|
known as NMN not to be confused with M&Ms the opposite effect and so NMN is
|
| 00:23:06
|
is what I take each day I take a gram of it but the thing with nicotinamide
|
| 00:23:11
|
mononucleotide NMN is that it it has this nicotinamide group on it it hangs
|
| 00:23:16
|
off the the main part of the chemical and it's the first bond to break and so
|
| 00:23:20
|
we see in animals and even in humans that the levels of nicotinamide go up
|
| 00:23:25
|
quite rapidly after taking NMN or NR and to look to high levels of
|
| 00:23:31
|
nicotinamide are not good in part because the nicotinamide gets excreted
|
| 00:23:37
|
through the kidneys and it's done so that happens because it becomes
|
| 00:23:42
|
methylated into methyl nicotinamide and methyl nicotinamide being used for for
|
| 00:23:47
|
years as a marker of all sorts of things including at least experimentally for
|
| 00:23:52
|
Parkinson's disease but the concern that's that's being talked about in
|
| 00:23:58
|
social media especially is is this drain of methyl nicotinamide a problem the
|
| 00:24:03
|
methyl groups are are needed for the body we need methyl for a whole range of
|
| 00:24:08
|
things including antioxidants and so as a precaution I take trimethylglycine so
|
| 00:24:14
|
that I continue to give my body a source of methyl groups now I don't know if
|
| 00:24:19
|
that's true people ask me all the time I take as a precaution because I know
|
| 00:24:24
|
that trimethylglycine is not going to hurt me glycine is good as a joke and
|
| 00:24:29
|
the other thing is methylglycine is also known as betaine which on human cells is
|
| 00:24:34
|
very good for them including protecting them against first so I don't see any
|
| 00:24:40
|
downside it's not an expensive molecule and the upside is that I'm preventing my
|
| 00:24:44
|
body from being drained of methyl groups but the reason that I can't say for sure
|
| 00:24:48
|
that it's necessary actually is that our bodies can make methyl groups there's a
|
| 00:24:53
|
whole pathway in fact I did a PhD on it when I was in Australia 30 years ago but
|
| 00:24:59
|
so I do take it as a precaution knowing that it's probably not doing anything
|
| 00:25:04
|
except goodness my boy great have you looked at methyl cobalamin or methyl
|
| 00:25:11
|
folate as a I have I have actually and I think those are interesting too I
|
| 00:25:15
|
couldn't say which is better in fact because nobody has studied it but those
|
| 00:25:19
|
are those are options to they're actually I've seen companies selling
|
| 00:25:24
|
those vitamins with methyls on them and those are vitamins that I think are
|
| 00:25:28
|
worth taking as well um so those are options I think you know like all
|
| 00:25:34
|
professors we like to say we need more studies before we know for sure but with
|
| 00:25:39
|
in the absence of studies I think those options are the best right now so thank
|
| 00:25:45
|
you for bringing up the topic of NAD one of my favorites for sure and I want
|
| 00:25:49
|
to express my deepest gratitude for you for helping inspire me to understand the
|
| 00:25:54
|
importance of this molecule I first recognized it when the importance of it
|
| 00:26:00
|
because of course we're taught in any biochemistry class when I watched one of
|
| 00:26:05
|
your videos four years ago but as I understand NAD was discovered about
|
| 00:26:09
|
almost a century ago by Otto Warburg but it only recently became to be
|
| 00:26:15
|
deeply appreciated as a fundamental strategy for all of health and longevity
|
| 00:26:19
|
I mean it's it's a coenzyme in over 500 metabolic reactions in the body so I'm
|
| 00:26:24
|
wondering from your perspective what do you believe was the catalyst for the
|
| 00:26:29
|
reemergence of the prominence of NAD and longevity well I'd like to think it was
|
| 00:26:34
|
work that I was doing with Lenny Guarente at MIT that's what I thought
|
| 00:26:38
|
and I set me up for but I guess you know that's what I actually put in one
|
| 00:26:43
|
of my new books is acknowledging you as the is really the catalyst for that well
|
| 00:26:48
|
it was a team and I'm not just being coy about that we we landed at the right
|
| 00:26:52
|
place at the right time we discovered genes that control aging in yeast cells
|
| 00:26:57
|
ironically that's where NAD was first discovered and I would argue that if
|
| 00:27:02
|
yeast weren't making alcohol we probably wouldn't have discovered NAD for a long
|
| 00:27:05
|
while but yeah the Germans just didn't discover NAD and we learned in high
|
| 00:27:10
|
school that NAD is essential for all these reactions so we knew that but what
|
| 00:27:14
|
we didn't realize until the late 1990s was that the levels of NAD in organisms
|
| 00:27:19
|
such as yeast and in our bodies as well they're really dynamic it's not just
|
| 00:27:25
|
that it's a housekeeping molecule keeping us alive during the day it's
|
| 00:27:28
|
going like this and in a yeast cell it's going like this and that was a shock
|
| 00:27:32
|
because first of all anything that's that important you think how can it go
|
| 00:27:37
|
up 50% or 100% during the day without killing us turns out it does and it's
|
| 00:27:42
|
actually very helpful and the reason that we think it goes up and down is NAD
|
| 00:27:47
|
isn't just making chemical reactions happen but there are proteins that sense
|
| 00:27:51
|
the amount of NAD in the cell and when times are tough we're hungry or we've
|
| 00:27:57
|
exercised NAD levels will actually go up and turn on these defenses and that's
|
| 00:28:03
|
why when you take a molecule like NMN or give an NMN to a mouse what we
|
| 00:28:08
|
think is happening is that you're tricking the body into thinking that
|
| 00:28:13
|
it's exercise or that it's hungry because the NAD levels will go up so you
|
| 00:28:17
|
get the benefit the protective benefits of these without actually having to
|
| 00:28:21
|
necessarily exercise or diet but if you're if you're wondering is it is it
|
| 00:28:26
|
fine just to take the pill and sit on the couch and eat potato the answer is
|
| 00:28:31
|
probably not we I mean in full disclosure we have published that
|
| 00:28:36
|
resveratrol and NMN that work through similar mechanisms do make mice
|
| 00:28:41
|
healthier even if they're fatter and don't exercise but here's the important
|
| 00:28:45
|
thing for those who want to maximize their body's potential maximize their
|
| 00:28:49
|
life we find that the combination of low calorie diets and these NAD boosters
|
| 00:28:56
|
or in the case of resveratrol we showed has a doubling effect they're actually
|
| 00:29:01
|
additive and so it's not no excuse just to sit around and just pop a pill okay
|
| 00:29:06
|
well I think you're right on I think that the optimizing in and most people
|
| 00:29:13
|
increasing NAD levels because it goes down pretty radically as you age to the
|
| 00:29:18
|
point where once you reach 80 I mean it's almost it's like now most not
|
| 00:29:23
|
there a radically decreased for at a minimum so you had mentioned NMN and
|
| 00:29:29
|
NRS precursors as one strategy to increase it but I'd like to discuss some
|
| 00:29:33
|
other options first is the actually the NAD molecule itself NAD plus which is a
|
| 00:29:39
|
charge molecule and if you swallow it it will not work at all as the success of
|
| 00:29:43
|
except it's being metabolized to its precursors and reconstituted but it can
|
| 00:29:48
|
be given parenterally either IV subq or transdermally and there's been a lot of
|
| 00:29:54
|
dispute in literature I'd like to get your view on it but a good friend of mine
|
| 00:29:58
|
who actually was just here last weekend James Clement who speaks very highly of
|
| 00:30:01
|
you by the way has doing a lot of research in NAD also and uses nitty
|
| 00:30:06
|
Brady's lab out in New South Wales to actually measure it and from his analysis
|
| 00:30:10
|
he finds that well first of all the NAD does seem to enter the cells and
|
| 00:30:14
|
there's a transporter which I didn't know about until he told me which is
|
| 00:30:17
|
connection 43 that substantiates the the strategy of using NAD plus itself
|
| 00:30:25
|
rather than an intermediary or precursor and we'll talk about some of the other
|
| 00:30:28
|
precursors there's more than just those that we're mentioning but you know it's
|
| 00:30:34
|
it's James assessment that the transdermal battery patch applied maybe
|
| 00:30:38
|
once or twice a week might be an optimal strategy to to improve it and you know
|
| 00:30:43
|
and he's documented by NAD mass spec measurements at Brady's lab so I'm
|
| 00:30:48
|
wondering what your thoughts on that right well so there are a variety of
|
| 00:30:53
|
ways to raise NAD and this list is not exhaustive but I'll talk about what
|
| 00:31:01
|
ones we know of that have been really tested it's fairly extensively so you
|
| 00:31:07
|
can raise NAD levels just by taking nicotinic acid or niacin and so niacin
|
| 00:31:15
|
has been used for decades to lower cholesterol and the only side effect is
|
| 00:31:20
|
flushing you feel a little bit warm there are slow release versions that
|
| 00:31:26
|
will raise NAD and actually there are some of us myself included that are
|
| 00:31:30
|
entertaining the possibility that the benefits you get are in part because it
|
| 00:31:35
|
also raises NAD but in head-to-head studies that I've read niacin won't
|
| 00:31:42
|
raise in 80 levels the way some of these other molecules do and I think the
|
| 00:31:48
|
reason is that niacin is just a tiny part of the NAD molecule and so you know
|
| 00:31:55
|
let me think of an analogy it'd be like saying I can build a house out of bricks
|
| 00:32:00
|
but if you don't bring the mortar and the windows and the doors and the roof
|
| 00:32:06
|
it's gonna be a lot harder and so the windows and the roof come in with
|
| 00:32:13
|
molecules like NR which is nicotinic riboside and NMN which is NR but with a
|
| 00:32:20
|
phosphate group added so now you've got more of the house built and you're
|
| 00:32:25
|
almost at NAD and so we're getting closer and so there's there's a debate
|
| 00:32:33
|
it's it's a bit of a silly debate which is better NR or NMN. In mice I can tell
|
| 00:32:38
|
you that that both work well to improve the health and the lifespan of mice
|
| 00:32:45
|
we've done a lifespan of NMN we haven't we're repeating it looks good NR is
|
| 00:32:51
|
published that it extends the lifespan of old mice so they're both great it's
|
| 00:32:55
|
really I think it's semantics to say that one is you know ten times better
|
| 00:33:01
|
than the other it's just not not the case they both get into cells there are
|
| 00:33:09
|
transporters for NR there's a new newly discovered transporter for NMN.
|
| 00:33:13
|
Ah that must have been the last few months I have not seen that. Right yeah
|
| 00:33:17
|
so it came out of Dr. Shin Imai's lab at Wash U Medical School and I wrote a
|
| 00:33:24
|
News and Views article on it it looked really convincing what we don't know
|
| 00:33:29
|
though is is this transporter in all cells or is it just in the gut and so
|
| 00:33:36
|
you know that remains to be seen but it that it really doesn't matter it's
|
| 00:33:42
|
it's irrelevant we can talk about transporters all day what really matters
|
| 00:33:46
|
is do you see health benefits and do you see NAD levels going up and I guess the
|
| 00:33:52
|
third important thing is are there any side effects or negative side effects I
|
| 00:33:57
|
haven't seen any negative side effects and I've certainly seen niacin NR and
|
| 00:34:01
|
NMN raise NAD levels and provide health benefits and as I mentioned NR and NMN
|
| 00:34:08
|
seem to be better than niacin. Well niacin does have problems there's no
|
| 00:34:13
|
question niacinamide even more as you well know and you've done the research
|
| 00:34:17
|
actually I think your lab showed this is that the niacinamide actually inhibits
|
| 00:34:22
|
sirtuins through a negative feedback loop. I'm impressed you've done your
|
| 00:34:28
|
reading. Yeah I've studied this I told you you really inspired me I mean I've
|
| 00:34:33
|
read hundreds of studies about this and that was one of them so the but the
|
| 00:34:38
|
niacin high doses is not without side effect aside from the flushing that you
|
| 00:34:43
|
mentioned which is actually a liberation of histamine from mast cells it
|
| 00:34:47
|
radically consumes methyl groups so not a good idea to take high dose niacin but
|
| 00:34:54
|
I've concluded and I might be wrong here I'd be interested in your thoughts and
|
| 00:34:57
|
then we'll go into the details dive deeper into the NR and NMN of taking a
|
| 00:35:04
|
very small dose of niacin 25 to 50 milligrams which shouldn't suck up too
|
| 00:35:08
|
many methyl groups but yet still can contribute to the at least a normal
|
| 00:35:14
|
human at least as I read about the 90 milligram loss of NAD plus per day
|
| 00:35:19
|
because we've got nine grams in our body but we recycle 99% of it so that niacin
|
| 00:35:24
|
is really only good for the salvage pathway so what are your thoughts on 25
|
| 00:35:27
|
to 50 milligrams maybe twice a day because the half-life of NAD is about 12
|
| 00:35:31
|
hours to use that as an augmentation strategy to the pre other precursors or
|
| 00:35:39
|
itself well so there are two ways to think about one is can you stimulate the
|
| 00:35:46
|
body to make more NAD because it is recycled and the other is which which
|
| 00:35:53
|
would I focus my thoughts on more which is if we give the the cells so much
|
| 00:36:02
|
precursor they have no no alternative but to put it into NAD and I think that
|
| 00:36:08
|
those two ways of thinking are your way in my way are guiding what we do I think
|
| 00:36:15
|
it's possible that low doses of nicotinic acid could stimulate the body
|
| 00:36:21
|
and force the cell to make more than it otherwise would but it would have to
|
| 00:36:27
|
make more than it otherwise would because the amount of NAD in your body
|
| 00:36:31
|
is you know it's in the gram amounts so milligram amounts are probably not going
|
| 00:36:36
|
you know by mass action push it up well that was one of the things that
|
| 00:36:41
|
discouraged me from even considering it as a practical strategy because there's
|
| 00:36:44
|
scrams in it so what it didn't make sense to me why taking milligrams of
|
| 00:36:48
|
something would be benefit but there appears to be a benefit let's could use
|
| 00:36:52
|
I'd be curious how that works so you know what my guess would be that you
|
| 00:36:56
|
know I'm gonna test it because James Clement has developed this elegant
|
| 00:37:00
|
blotter strategy where you can can essentially pipette a dropper to a blood
|
| 00:37:06
|
on a blotter freeze it and he's getting a mass spec in his lab and he's going to
|
| 00:37:10
|
be able to measure it so I'm gonna do the test this fall and and see if it
|
| 00:37:14
|
makes a difference I mean I just don't know it's just theoretical at this point
|
| 00:37:17
|
yeah well when it comes to NMN which we've studied for a lot and there are
|
| 00:37:22
|
studies on NR in humans and I've seen insights into NMN in humans as well
|
| 00:37:26
|
though that work isn't yet published I what can I reveal I can reveal that that
|
| 00:37:34
|
taking doses say less than 250 milligrams don't have a big effect on
|
| 00:37:40
|
NAD in the blood that would make sense you do have to take high doses but it's
|
| 00:37:46
|
complicated by the observation that a single dose won't have a big long-lasting
|
| 00:37:53
|
effect anyway we see that in mice as well you take one hit of NMN it'll go up
|
| 00:38:00
|
maybe go about 50% and it'll quickly die die away in levels but what's
|
| 00:38:05
|
interesting in the mouse and the human studies is it's more like a positive
|
| 00:38:10
|
stock market where over a period of in the case of the NR study that I'm
|
| 00:38:16
|
thinking of after nine days it was an accumulation up to a certain level and
|
| 00:38:22
|
so if a study has only done a one time point in a human or in a mouse be
|
| 00:38:27
|
careful because that's probably misleading and that you know you want to
|
| 00:38:32
|
measure these things after at least nine days and hopefully after a few months
|
| 00:38:36
|
where any of maybe Joe that those low doses actually start to kick in yeah
|
| 00:38:41
|
what do you think the optimal dosing strategy is every 12 hours or three
|
| 00:38:45
|
times a day well you know that's also not known and I probably know more than
|
| 00:38:51
|
most people on the planet I don't know that's what I'm asking yeah so what do I
|
| 00:38:56
|
do I take a bolus in the morning I take a gram in the morning I know a gram is
|
| 00:39:00
|
likely to be raising my energy levels during day I also try to time it with my
|
| 00:39:05
|
natural circadian rhythm so NAD will go up during the morning getting ready but
|
| 00:39:12
|
if I take it at night what I find is that I'm actually starting to interfere
|
| 00:39:19
|
with my sleep patterns interesting yeah and a lot of people have told me that
|
| 00:39:23
|
that's the case as well with resveratrol as well it actually makes sense there's
|
| 00:39:27
|
a few science papers on this about sort one which is the target one of the NAD
|
| 00:39:34
|
requiring enzymes that we study so so one is also its activities cycling
|
| 00:39:39
|
through the day with NAD turning on genes are required for morning activities
|
| 00:39:46
|
at night clearing the brain at night you think if you get those out of kilter I
|
| 00:39:51
|
mean it makes sense that you will not only affect your body's metabolism find
|
| 00:39:58
|
it hard to sleep but you could even start to have the effects of jet lag
|
| 00:40:02
|
inadvertently I'd like to think that by taking the NAD boosters when I'm
|
| 00:40:08
|
traveling I'm actually resetting my body's clock and I do find you know for
|
| 00:40:13
|
me in my experience I do feel better if I reset my clock with an NAD booster
|
| 00:40:18
|
when I arrive at in a new time zone so how does that reconcile with the fact
|
| 00:40:25
|
that NAD plus levels increased by about 30% at least that's what I've read in
|
| 00:40:29
|
the literature once you're fasting so you know I'm just trying to reconcile
|
| 00:40:34
|
that in fact that you're having challenges with NAD plus at night
|
| 00:40:38
|
because of a sleep in effect yeah well so I'm I don't think anyone's done it
|
| 00:40:46
|
24-hour time course of any in people in mice we do know that it's cycling
|
| 00:40:53
|
through the day you know let's see we're right on the cutting edge here you know
|
| 00:40:59
|
you have a choice you can take it at night or in the morning and I think that
|
| 00:41:09
|
probably what's happening is if I take it just before I go to bed my body's not
|
| 00:41:16
|
in a fasting state yet it's still got you know my dinner is still in there and
|
| 00:41:21
|
so it's a it's mimicking fasting it's raising in 80 levels just when it should
|
| 00:41:25
|
should be starting to to tailor off I think probably what's happening Joe's
|
| 00:41:30
|
now I'm thinking out loud is towards the early morning your NAD levels are going
|
| 00:41:35
|
to start coming up because that's when your stomach's empty and you've absorbed
|
| 00:41:39
|
a lot of nutrients overnight as it's coming up towards you know waking up and
|
| 00:41:43
|
early morning that's when I provide my boost okay catch it on the rise
|
| 00:41:50
|
certainly a rational approach and then I try not to eat till lunch so I get that
|
| 00:41:54
|
big spunk okay I want to dive in the weeds now on NMR and NMN and NR I had a
|
| 00:42:02
|
chance to attend a lecture by Charles Brenner earlier this month and talked to
|
| 00:42:07
|
him afterwards and because many people use NR not as many NMN but most of the
|
| 00:42:16
|
studies done on at least NR I haven't really reviewed much of the NMN
|
| 00:42:20
|
literature but the NR it's usually perennially it's intraperitoneal or IV
|
| 00:42:27
|
it's not orally I mean there's some but it's not a large amount of them are done
|
| 00:42:31
|
orally so and and the problem with it is as I understand is that when you swallow
|
| 00:42:35
|
NR and and this has some implications for NMN too that the first bypass it
|
| 00:42:42
|
goes through the liver and the liver methylates it so the liver gets plenty
|
| 00:42:46
|
of NAD plus but you know the the amount that goes to other organs seems to be
|
| 00:42:52
|
pretty diminished which suggests to me that a either a perennial or
|
| 00:42:58
|
transmucosal approach might be a superior delivery method so which is one
|
| 00:43:03
|
of the reason and I asked Brenner this after his presentation what he thought
|
| 00:43:07
|
about transmucosal delivery and he said he doesn't know he thought about it and
|
| 00:43:10
|
I told him that I was using rectal NR suppositories that I make myself and
|
| 00:43:16
|
he thought the compliance with that would be pretty horrible but I suspect a
|
| 00:43:20
|
similar story is with going with NMN and I'm wondering what your thoughts are on it.
|
| 00:43:25
|
Well so we're doing the experiments that are required to actually conclude
|
| 00:43:32
|
provide answers to those questions we don't know okay so what is the answer
|
| 00:43:37
|
but but the experiments that are ongoing in my lab also in Anthony Sauve's lab in
|
| 00:43:42
|
Cornell we we have labeled molecules labeled NMN we're giving that initially
|
| 00:43:50
|
to animals and mice eventually we could do humans as well and those are the
|
| 00:43:56
|
studies you need to be able to say yeah NMN's going straight into cells or is it
|
| 00:44:01
|
getting modified it's early days we think that it's a lot of it goes
|
| 00:44:06
|
straight in contrary to what people are gossiping about but you know we have to
|
| 00:44:11
|
do the hard science I don't think it's good to just hand wave and say
|
| 00:44:14
|
conclusions that aren't yet justified without the hard science.
|
| 00:44:18
|
Fair enough.
|
| 00:44:19
|
On the NMN side you probably noticed from the literature that we typically put NMN in
|
| 00:44:25
|
drinking water.
|
| 00:44:26
|
Yeah, because it's a water soluble.
|
| 00:44:28
|
Yeah, so it's very soluble but it's also more stable than NR in liquid.
|
| 00:44:32
|
So we have the advantage that we can do that.
|
| 00:44:35
|
NR in liquid is highly unstable and that's probably the reason that it's not done typically.
|
| 00:44:42
|
That way.
|
| 00:44:43
|
You know but that said, we don't know what happens in the microbiome when it's ingested
|
| 00:44:50
|
either are those bacteria utilizing it converting it is it different between people's microbiomes
|
| 00:44:56
|
we all have different microbiomes and that's the exciting part of the research now is to
|
| 00:45:01
|
figure out once you put one of these molecules into the system where does it go where are
|
| 00:45:06
|
the best effects and these are important because it'll guide not just the use of the
|
| 00:45:12
|
molecules in daily life as they are now solder supplements but what I'm focused on is making
|
| 00:45:21
|
molecules that will be drug like and used as drugs that could treat different diseases
|
| 00:45:26
|
and if one molecule is better for liver one molecule is better for muscle one gets into
|
| 00:45:31
|
the brain if there are ways we can tweak the molecule and change one atom to make it
|
| 00:45:35
|
last for two weeks instead of two hours that's the exciting future that I see and that's
|
| 00:45:43
|
what I spend most of my time on.
|
| 00:45:47
|
I'm not I mean in full disclosure everyone should know even if you see my name on a website
|
| 00:45:51
|
I have no affiliation to any supplement company I'm trying to do the science and stick with
|
| 00:45:57
|
clinical trials only at this point.
|
| 00:45:59
|
So you have no financial interest in NMN?
|
| 00:46:02
|
No well yeah I have biotech companies that I'm an advisor to and have licensed patents
|
| 00:46:09
|
to the chance that I'll see money out of that's pretty low most biotechs fail so I'm not driven
|
| 00:46:16
|
by that but I've never received a cent from supplements and you know one of my patents
|
| 00:46:22
|
was licensed to a company once and I said I want that money to go to research in my
|
| 00:46:27
|
lab instead I just think it's better for me Joe because I want to be able to maintain
|
| 00:46:34
|
sure the distance and be able to just talk about the science with some credibility.
|
| 00:46:38
|
Absolutely yeah I heard your podcast with Peter Ortea and you went into that great detail
|
| 00:46:43
|
and there are a lot of claims being made that you're recommending a specific NAD supplement
|
| 00:46:49
|
and if you see a claim like that it's it's not true it's false and you spend a good portion
|
| 00:46:53
|
of your resources to send cease and desist letters for those so I'm sorry you're going
|
| 00:47:00
|
to have to go through that but I want to get back to just finish up NAD and we're going
|
| 00:47:04
|
to go into sirtuins and then gene editing.
|
| 00:47:08
|
Do you I just did you didn't mention any thoughts on the IV or subcutaneous or transdermal NAD
|
| 00:47:14
|
plus itself the entire whole NAD molecule though the you know that you're using the
|
| 00:47:18
|
precursors to create and with the transporter of connexin 43 being there and lots of anecdotal
|
| 00:47:26
|
evidence especially in those with substance abuse getting benefits from these these strategies
|
| 00:47:30
|
I'm wondering what your thoughts are on the whole molecule being given.
|
| 00:47:34
|
Yeah well you know I'm the kind of scientist I don't have an ego in this if someone can
|
| 00:47:39
|
show me data that's reproducible and reproduced in other lives you know I'll take it on face
|
| 00:47:44
|
value and so I've heard the anecdotes on NAD and that's it seems like there's so many
|
| 00:47:51
|
stories out there that you know there's something there what I'd like to see is just like I'm
|
| 00:47:56
|
doing with NMN you know doing rodent studies and like James is doing James Clement doing
|
| 00:48:05
|
human studies and ultimately putting these molecules head to head yeah it's really it's
|
| 00:48:13
|
can get a little annoying when you know Dr. X says this and Dr. X says that.
|
| 00:48:18
|
Right right because you got to have data to back it up.
|
| 00:48:20
|
Yeah I mean show me them head to head yeah that's the only way I don't care what your
|
| 00:48:25
|
opinion is show me the data so that that'll be the ultimate test the problem is that these
|
| 00:48:30
|
trials are really expensive and typically doing one molecule is hard enough but doing two in
|
| 00:48:35
|
parallel is hard even in a mouse study we don't typically do that but that's where we need to go
|
| 00:48:41
|
to be able to to be able to say which is the best it really wouldn't surprise me if NR and NMN's
|
| 00:48:48
|
NADID are all beneficial in slightly subtle ways.
|
| 00:48:56
|
All right well thanks for that and I hope to with James do some of this research this year
|
| 00:49:01
|
and maybe this fall share some of that data with you so that we can have some hard science to back
|
| 00:49:06
|
it up. Now I want to shift to sirtuins which are essentially protein environmental stress
|
| 00:49:13
|
sensors that are responsible for longevity longevity proteins in simpler terms and
|
| 00:49:19
|
I guess they were discovered in yeast as SIR which is silent information regulators
|
| 00:49:26
|
and it suggests they work by suppressing DNA expression and this is typically done by
|
| 00:49:34
|
deacetylating the DNA and other proteins. Now you did not discover resveratrol but you clearly
|
| 00:49:43
|
your lab identified its effect on SIRT1 one of the seven important sirtuins in humans
|
| 00:49:49
|
so resveratrol happens to to be one of the polyphenols that do it but are you familiar
|
| 00:49:57
|
with any other polyphenols like quercetin or fisetin that have shown to have some impact and
|
| 00:50:03
|
I want to discuss about some of the derivatives of resveratrol that you might be working on.
|
| 00:50:09
|
Well yeah you've come to the right person to talk about that. So resveratrol was already
|
| 00:50:14
|
known as what's called a phytoalexin it seemed to have antioxidant properties and was even
|
| 00:50:21
|
thought at the time to be responsible I think some people still believe it's responsible for
|
| 00:50:25
|
the French paradox where the French apparently can eat fatty foods and have great cardiovascular
|
| 00:50:31
|
health on average. So that was all there in the late 80s. I came along well you know the mid 90s
|
| 00:50:40
|
probably was the was the real thing when 60 Minutes did a story on it. So I came along in the late
|
| 00:50:46
|
1990s or 2000s and we weren't looking at resveratrol in fact I'd never heard of resveratrol when we
|
| 00:50:51
|
started working on it. The story goes like this it's a pretty funny story. We had purified the
|
| 00:51:01
|
SIRT1 enzyme from humans and we were looking in collaboration with a company called Biomole
|
| 00:51:08
|
and the lead scientist there was Conrad Howards he deserves a lot of
|
| 00:51:11
|
credit for this. We were looking for molecules that would inhibit the enzyme and it was a
|
| 00:51:17
|
collaboration and we were sharing stories and results and Conrad calls me one day and he says
|
| 00:51:24
|
are you sitting down? I went I am sitting down what's up? And he goes we've got these strange
|
| 00:51:28
|
molecules that may activate the enzyme and then I that that was of course music to my ears because
|
| 00:51:35
|
we didn't know that NAD could be used at that point we were just on the verge of discovering
|
| 00:51:40
|
that. But what we did know that was that we wanted to activate these enzymes because they're
|
| 00:51:45
|
beneficial. We knew in yeast and in worms that if we put and in flies if you put extra copies of the
|
| 00:51:52
|
SIRT2 and gene they would live longer so we wanted more more goodness. But finding activators
|
| 00:51:59
|
of enzymes is extremely rare I think there's only a few examples in the whole history of
|
| 00:52:04
|
pharmaceutical development and when you find one typically people call BS on you. But here was
|
| 00:52:10
|
Conrad saying that we've got something. So we tested it in the lab and we could repeat his
|
| 00:52:15
|
results yes it was an activator. But to really show that it was true we had to put it on some
|
| 00:52:22
|
yeast cells and on some human cells and we did that and we found that it extended their lifespan
|
| 00:52:29
|
in the case of yeast and in the case of human cells protected them. And you needed the SIRT1 gene
|
| 00:52:35
|
for that to work so it wasn't just an antioxidant effect it was actually through the same
|
| 00:52:40
|
mechanism that we were hoping it was. But you asked Joe about these other molecules. Well we
|
| 00:52:46
|
tested with Conrad well we screened about 18,000 of them and published 21 activators in that first
|
| 00:52:55
|
paper in Nature Journal 2003. Now resveratrol was the best one we had at the time and it got the
|
| 00:53:02
|
most attention because the red wine story was pretty funny and interesting to the media. But
|
| 00:53:08
|
there are there were others that were very close to resveratrol in structure and in potency. You
|
| 00:53:14
|
mentioned quercetin, fazetin, or vicetin. These are plant molecules as well. They're all produced
|
| 00:53:23
|
in response to stress when the plants are stressed dehydration or UV light and they seem to have
|
| 00:53:29
|
benefits on organisms when we consume them. Interestingly what has later been discovered
|
| 00:53:35
|
though rarely acknowledged is that these same molecules work on killing senescent cells. You
|
| 00:53:40
|
know that your viewers will know of senescent cells the zombie cells that accumulate in our
|
| 00:53:45
|
body and cause havoc. Now others have shown that quercetin, gyncroclin, and others have
|
| 00:53:51
|
senolytic properties same with fazetin. But what's not recognized typically or admitted is that these
|
| 00:53:58
|
molecules were discovered 15 years ago to also be SIRT1 activators. So I thought so. Yeah so it's
|
| 00:54:04
|
really interesting. Now what I think is going on is evidence for a hypothesis that Conrad Howitz
|
| 00:54:12
|
and I came up with which we published in Cell I think it was the year 2005. Anyway the idea is
|
| 00:54:20
|
called xenohormesis. X-E-N-O-HORMESIS. And it's the idea that we've evolved to sense our environment
|
| 00:54:27
|
and molecules that are produced by plants and bacteria in our environment when they're stressed.
|
| 00:54:33
|
If we consume those or put them on our skin for example our bodies will recognize those. We've
|
| 00:54:38
|
evolved to sense our world around us. And that's a very good way of getting a heads up if your
|
| 00:54:43
|
plants are running out of nutrients or the water table is drying up. And you know before we were
|
| 00:54:49
|
conscious and we had brains this was the best way for a worm or a fly to know that times were
|
| 00:54:56
|
probably going to deteriorate. And what you want to do is get ready for those times of adversity
|
| 00:55:01
|
before they actually happen. And so that can explain why so many molecules from the plant
|
| 00:55:08
|
world have given rise to medicines and why some molecules like resveratrol and quercetin, fazedin,
|
| 00:55:14
|
even aspirin have remarkable health benefits and target many different enzymes in the body.
|
| 00:55:20
|
That seems to be well beyond what coincidence could explain. Interesting. So there is probably
|
| 00:55:28
|
not a better person in the world to ask this question to but you so eloquently describe
|
| 00:55:33
|
sirtuins as environmental stress sensors. And when I heard that description it immediately
|
| 00:55:40
|
occurred to me that that's very similar to heat shock proteins, almost identical.
|
| 00:55:45
|
And heat shock proteins of course for those who don't know are really important to fold your
|
| 00:55:51
|
proteins back to the right conformation so they work properly. And I'm wondering if there's any
|
| 00:55:56
|
similarities or am I just making this thing up? Yeah I want to quickly look at the literature
|
| 00:56:03
|
because I recall that there were connections between sirtuins and heat shock proteins. I
|
| 00:56:07
|
can't remember which controls which but they're connected. But in principle you're right Joe that
|
| 00:56:14
|
this is all evidence of hormesis that you can stimulate the body's ability to
|
| 00:56:19
|
fight against problems. So it's thought that a little bit of heat, even a little bit of cold,
|
| 00:56:26
|
a little bit of hunger, some exercise, some hypoxia, lack of oxygen in your body. These are all ways of
|
| 00:56:33
|
activating these defense pathways. The same pathways that we've talked about before such as
|
| 00:56:38
|
sirtuins, there are seven of those which by the way NAD and resveratrol will both activate.
|
| 00:56:46
|
Just to recap the mTOR which lower amino acids particularly leucine and arginine and the AMP
|
| 00:56:52
|
kinase pathway so metformin and inhibition of complex one. So these are the main three
|
| 00:56:58
|
defensive pathways. There are others but what's downstream of these pathways are things like heat
|
| 00:57:03
|
shock proteins and transcription factors that turn on DNA repair enzymes. There's a whole litany
|
| 00:57:09
|
actually that there's a thousand papers per year on what are these sensors as we call them, what do
|
| 00:57:16
|
they do downstream and here's the good news actually. We used to think that we had to
|
| 00:57:22
|
understand what everything those sensors do to be able to understand aging and be able to live
|
| 00:57:28
|
longer but what I've been arguing actually for many years now is that we don't need to fully know what
|
| 00:57:33
|
they do. Heat shock proteins are great, definitely part of it but we don't need to know everything.
|
| 00:57:38
|
As long as we can find the right nodes in the cell to turn them on in the right ratios at the right
|
| 00:57:44
|
time, the body has evolved to take care of the rest and we're getting to the point fortunately,
|
| 00:57:49
|
it's been really remarkable to see where we know what these nodes are, we have the tools to tweak
|
| 00:57:55
|
them, we can also change them naturally by fasting and exercising, we change them with molecules that
|
| 00:58:00
|
we can ingest or inject but now the cutting edge is now with this toolbox when do you apply them
|
| 00:58:08
|
and how much and in what combinations and that's really what people like myself and you and and
|
| 00:58:14
|
your listeners are on to right now. Okay, I want to go back to NAD for a moment because there's an
|
| 00:58:20
|
important component that I neglected to discuss with you and that is another strategy for increasing
|
| 00:58:26
|
NAD plus levels is to not use it as much and from my review of the literature one of the primary
|
| 00:58:33
|
consumed, well there's two primary ones, the inside the cell would be PARP, poly ADP ribose polymerase
|
| 00:58:39
|
which is a DNA repair enzyme and it really designed to repair DNA breaks single and double
|
| 00:58:44
|
stranded and every time you have a break it's my understanding that you the PARP will take
|
| 00:58:50
|
suck out 100 to 100 ADP out of 100 to 150 NAD molecules and basically deplete your level by
|
| 00:58:57
|
that much for every break so and then you've got TD38 for extracellular consumptions which
|
| 00:59:03
|
has to do with the immune system but I'm wondering what your thoughts are on lowering PARP
|
| 00:59:09
|
activation and real common not widely appreciated but what I'm passionate about is really topic of
|
| 00:59:17
|
my next book is EMF exposure. I mean it's pretty well documented in the literature that I've reviewed
|
| 00:59:22
|
that it does activate PARP and decreases NAD level so in my view if you could limit that exposure
|
| 00:59:29
|
because you're not decreasing increasing consumption you're going to by default
|
| 00:59:33
|
increase NAD levels. Yeah right well yeah this is a really interesting topic that and I could
|
| 00:59:40
|
talk all day about it. So PARP enzymes you're right there's DNA repair protein the problem is when you
|
| 00:59:47
|
hyperactivate this protein there's PARP1, there's PARP2, there's actually more than 14 different
|
| 00:59:53
|
PARPs. They do drain NAD quite effectively in fact in my lab we've discovered another PARP that
|
| 00:59:59
|
when you have inflammation it drains NAD as well so it does make sense to slow them down as you're
|
| 01:00:07
|
mentioning in some cases inhibit them but you have to be really careful because you do need them.
|
| 01:00:13
|
We only why would you want to inhibit them because why would you want to inhibit DNA repair?
|
| 01:00:17
|
Well you wouldn't but you want to inhibit their overuse of NAD. Right by decreasing these
|
| 01:00:24
|
insults that would cause them to be activated. That's the best way right because then you get
|
| 01:00:28
|
the benefits of low DNA damage and the benefits of high NAD. We had a science paper in 2013 that
|
| 01:00:34
|
connected all of this together that the sirtuin gene or the sirtuin enzyme this sort one we've
|
| 01:00:40
|
talked about actually controls PARP activity and PARP1 is normally inhibited by a protein called
|
| 01:00:48
|
DBC1 and then sirtuin one controls that process and long story short you want to activate PARP
|
| 01:00:58
|
but not too much and so that's what we think is going on here this fine tuning but actually to
|
| 01:01:03
|
get to what's really more interesting I think is how do you keep your levels of DNA double
|
| 01:01:07
|
strand breaks to a minimum and I think that's the key one of the main keys to longevity
|
| 01:01:15
|
and there's two reasons one you mentioned which is that double strand breaks drain NAD.
|
| 01:01:21
|
The second which I think you're going to be familiar with because you've read my upcoming
|
| 01:01:27
|
book is the idea that DNA double strand breaks also disrupt the cell's epigenome the storage of
|
| 01:01:36
|
the information that we get passed down from our mothers and fathers mother and father
|
| 01:01:44
|
and the packaging of the DNA. We can get to that in a minute but basically
|
| 01:01:49
|
what happens is if you have a broken DNA proteins such as the sirtuins will leave their normal
|
| 01:01:57
|
sites where they're regulating genes and they'll go help repair with PARP as well but then they
|
| 01:02:03
|
don't all find their way back to where they came from they actually some of them get lost and get
|
| 01:02:08
|
distracted and over time what we see is that these proteins are essential for maintaining
|
| 01:02:13
|
cellular identity and cellular function will be lost and we see that in yeast cells. Yeast
|
| 01:02:18
|
cells get old because they're moving between breaks and back again to these to genes so it's
|
| 01:02:24
|
twofold so before we get to the science and I'd love to touch on that the key ways to reduce
|
| 01:02:31
|
double strand breaks I think I don't know about the radiation I have to trust you on that one but
|
| 01:02:36
|
CT scans. It's ionizing radiation I'm talking about non-ionizing but they both do it
|
| 01:02:42
|
different mechanisms ionizing does it through hydroxyl free radicals and non-ionizing does it
|
| 01:02:48
|
through carbonyl carbonate free radicals primarily through peroxynitrite. Yeah makes sense there's a
|
| 01:02:53
|
lot I mean you can't avoid DNA breaks in our body every day we have about a trillion breaks
|
| 01:02:59
|
you know one per cell at least and just living DNA will break especially when it's replicating
|
| 01:03:06
|
itself and the cell divides you'll have a break so even if you live in a lead box at the bottom
|
| 01:03:10
|
of the ocean which I don't recommend doing but you can minimize it you know I go through the
|
| 01:03:17
|
the DNA scanners occasionally and I ask the people there and I've researched this as well
|
| 01:03:23
|
the amount of radiation is about the same as you get on the flight but but why double your exposure
|
| 01:03:28
|
you know to me it doesn't make sense so I try to if I can avoid that exposure x-rays dental x-rays
|
| 01:03:36
|
you know they're important I'm not going to deny that and I think that we should know what's in our
|
| 01:03:41
|
mouth but I would try not to overdo it I think any physician who does x-rays should have a good
|
| 01:03:47
|
reason for doing it and usually they do but you know be aware that there are consequences to
|
| 01:03:55
|
exposing your body to radiation. Okay so let's get to what you just alluded to which is the
|
| 01:04:01
|
resolution of some of the epigenetic damage that accumulates through through age and what I think
|
| 01:04:08
|
is one of the most fascinating aspects of your book in which you are using technology that I
|
| 01:04:13
|
believe developed by another researcher in your lab Dr. George Church who developed the Chris and
|
| 01:04:20
|
co-invented as I understand the CRISPR technique and you're using those gene editing techniques to
|
| 01:04:27
|
insert three of the four Yamanaka transcription factors into aged mice that have either been
|
| 01:04:35
|
experimentally or are blind in some way and you can actually restore their vision through this
|
| 01:04:41
|
epigenetic resurrection. Yeah so we're writing up three papers now and so this is a sneak preview of
|
| 01:04:49
|
what hopefully will be published later this year and what we've discovered over the last 10 years
|
| 01:04:55
|
and this has been a 10-year project so I'm really grateful to the scientists in my lab who've had the
|
| 01:05:01
|
endurance we've discovered what we think is is very strong evidence for what we call now
|
| 01:05:07
|
epigenetic noise as a cause of aging not just in mammals but throughout life even in yeast cells.
|
| 01:05:15
|
So what does that mean? So let's just quickly do a biology lesson for those who haven't been in high
|
| 01:05:20
|
school for a while. So the genome we know DNA genome epigenome is the organization of that DNA
|
| 01:05:28
|
and the epigenome tells the cell that they should turn on this gene to be a nerve cell and in a liver
|
| 01:05:34
|
cell turn on that gene to be a liver cell and that's epigenetics and cells inherit that information
|
| 01:05:39
|
just as much as they inherit their DNA. So in my book what I am proposing is that those two types
|
| 01:05:47
|
of information genomic and epigenomic they're quite different. The genomic the DNA is digital
|
| 01:05:55
|
which is very well preserved and can last a long time we know that DVDs last longer than cassette
|
| 01:06:01
|
tapes but the problem for the epigenome is that it's analog information and anyone who's had a
|
| 01:06:06
|
cassette tape or a record knows that you can you can pretty easily scratch these or lose the
|
| 01:06:13
|
information in fact you can scratch your DVD and lose the information. We actually think that aging
|
| 01:06:20
|
is similar to those scratches that the information to be young again is still
|
| 01:06:24
|
largely in our bodies but we can access our cells can access that information just by you know
|
| 01:06:31
|
metaphorically scrubbing the DVD or polishing it up so that the cell can read the right genes
|
| 01:06:37
|
in the case of the DVD the right song. So with that in mind let me explain what we've discovered
|
| 01:06:45
|
if so we literally have not literally but metaphorically have a way of scratching
|
| 01:06:50
|
a mouse's epigenome and the way we do that is actually we cut the DNA we create these double
|
| 01:06:55
|
strand breaks let the cell heal them without making mutations so there's no change to the
|
| 01:07:00
|
digital information but what we see is the process of proteins moving around and trying to repair
|
| 01:07:05
|
that DNA eventually introduces this epigenomic noise and the genes that were once on many of
|
| 01:07:12
|
them get turned off and those that were once off come on and so liver cells start to lose
|
| 01:07:16
|
their identity skin cells start to lose their identity and the consequence we think is aging
|
| 01:07:21
|
and we actually will hopefully publish a paper that shows that if you create this noise in a
|
| 01:07:26
|
mouse it will go through accelerated aging and not just looking old it is actually literally
|
| 01:07:33
|
old if we measure the the epigenetic clock and I think many of your listeners and viewers will
|
| 01:07:40
|
know that there's a clock you can measure from blood in our bodies or in a mouse and it'll tell
|
| 01:07:45
|
you how old the animal is or we are biologically if we do that with our mice that we've scratched
|
| 01:07:51
|
up they are literally not likely 50 older which is great okay but you might say well
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| 01:07:59
|
David that that's all fun but why do we care about making a mouse older well first of all it's good
|
| 01:08:04
|
evidence that we're right about the hypothesis that every aspect of aging is recapitulated
|
| 01:08:10
|
second of all we have mice now that we can change the rate of aging perhaps even accelerate aging
|
| 01:08:15
|
so that they behave more like humans and we can potentially have a better mouse model for
|
| 01:08:20
|
Alzheimer's for example but then the third thing is if you can give an animal something then you
|
| 01:08:27
|
can actually with that knowledge take it away and that's what we've done with George in collaboration
|
| 01:08:32
|
with George what we did actually was we wanted to reprogram the cells so that the genes that were
|
| 01:08:38
|
once let's start with this the ones on now they they go back off and vice versa so genes that were
|
| 01:08:46
|
once off come back on and what we find is that by using these three yamanaka factors you can
|
| 01:08:53
|
actually find the original information in the cell that tells it to be young again and those genes
|
| 01:08:58
|
actually switch and the cell behaves like it's young again and in the case of the the retina
|
| 01:09:04
|
we have preliminary results that we can actually restore eyesight by rejuvenating the nerves in
|
| 01:09:12
|
the retina to be young again and so that's early days of what I hope is the future where we can
|
| 01:09:19
|
reprogram cells in the body doesn't have to be the retina can be any cell type in the body you think
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| 01:09:24
|
to actually not just act young but literally be molecularly young again and in my career
|
| 01:09:31
|
I've seen a lot of cool stuff and I haven't seen anything this cool before I couldn't agree more
|
| 01:09:36
|
it's the potential is beyond extraordinary and I'm wondering if the cells that you're
|
| 01:09:42
|
injecting are they pluripotent stem cells that you're modifying with the yamanaka transcription
|
| 01:09:48
|
factors we're actually we're actually just giving uh the the genes to the organism we're turning on
|
| 01:09:56
|
oh with a virus adenovirus we do we use the virus that's that's used by pharmaceutical companies to
|
| 01:10:02
|
correct genetic diseases so it's a an FDA approved virus that that is very easy to use in the eye
|
| 01:10:11
|
actually one injection there's no immune response in the eye it's not a big one and so that's why
|
| 01:10:16
|
we chose the eye actually it's not just that we we saw it as a challenge to reverse blindness
|
| 01:10:22
|
but we also knew that it could be the quickest path to uh to testing this in people and helping
|
| 01:10:29
|
them with this new technology so is this mostly a local effect that you're achieving
|
| 01:10:35
|
uh well in the eye yes uh and and by design um you don't know the full safety profile yet so we want
|
| 01:10:41
|
to be careful but we have injected mice intravenously with the virus and we've got mice that
|
| 01:10:47
|
are healthy 10 months later and so far so good you know it's early days we've only been testing
|
| 01:10:52
|
it on about 100 mice we have a lot more to do and it's many years of work to make sure it's safe
|
| 01:10:57
|
but uh yeah i think the promise is there and it's just hopefully evidence if not proof in principle
|
| 01:11:05
|
that aging is more reversible than we ever thought do you have plans on putting genes in to make
|
| 01:11:15
|
additional sirtuins like all the seven her two seven sirtuin genes in humans uh to augment those
|
| 01:11:21
|
i mean that's going to be better than a than a sirtuin activator if you can have them be on all
|
| 01:11:26
|
the time wouldn't it be yeah it would i only use viruses when absolutely necessary i think
|
| 01:11:32
|
the well-trodden path of small molecules means that there's a much greater chance of success
|
| 01:11:37
|
and less chance of side effects and toxicity with viruses as great as they are and as how
|
| 01:11:43
|
exciting they sound it's still a pretty it's still early days we don't know that so i i don't
|
| 01:11:51
|
see a use for um viruses and sirtuins in humans at this point but i so i'll stick with small
|
| 01:11:57
|
molecules but what i do see a future you know if you want to go crazy with predictions yeah yeah
|
| 01:12:04
|
that that we we could see a world where where people do choose to be genetically modified um
|
| 01:12:11
|
it's their choice right you wouldn't i don't think you can easily go in and modify children
|
| 01:12:15
|
even though that's now being done unless it's life-threatening of course but adults you know
|
| 01:12:21
|
they should be able to have a choice if there's if there's safety and it's approved then they should
|
| 01:12:26
|
be able to do that and maybe there'll be a day when we are able to carry these yamanaka genes
|
| 01:12:33
|
in our body and when we get sick or we have an injury uh let's say we have a detached retina or
|
| 01:12:40
|
we have a broken spine uh then we get an iv that turns on those genes for a month we recover
|
| 01:12:46
|
we rejuvenate and then we turn them off again until we need them again and that would be a
|
| 01:12:52
|
pretty wild sci-fi future but science is pointing to at least the biology being possible i believe
|
| 01:13:01
|
you mentioned that there's no rational biological requirement for death that not necessarily
|
| 01:13:11
|
mortality but you could live hundreds of years theoretically so i'm wondering in your mind what
|
| 01:13:16
|
you perceive as the best bridge to pass this the clearly 120 year limit that humans currently have
|
| 01:13:24
|
would it be uh resetting the that epigen the methylation clock the horvath methylation
|
| 01:13:31
|
clock back to zero with like hematopoietic stem cells or what do you think is the
|
| 01:13:37
|
biggest step to do that right well so i put my money on on the DNA methylation reprogramming
|
| 01:13:46
|
right now it's uh you know i've seen old mice regain their eyesight i haven't seen any technology
|
| 01:13:53
|
able to do that previously so if you applied that technology in combination with some of the
|
| 01:14:01
|
molecules we've talked about today in combination with a healthy lifestyle that we're trying to
|
| 01:14:06
|
optimize in real time here i don't think anyone can say what what our limit is i mean anyone who
|
| 01:14:14
|
says that there's a limit really doesn't know what they're talking about or is lying we really
|
| 01:14:19
|
don't know what's possible people who have lived in to 110 115 they typically smoke they've done
|
| 01:14:25
|
no exercise they had a lot of alcohol uh do you does anyone think that if they didn't have access
|
| 01:14:33
|
to the kind of things that we're talking about today they couldn't have lived longer i think
|
| 01:14:37
|
they definitely could have we just don't know because those people are so rare and typically
|
| 01:14:43
|
they didn't expect to live so long in the first place um so yeah now now with what we know and
|
| 01:14:49
|
what people in the future will know i mean why not and the longer we live the more access we
|
| 01:14:54
|
have to this technology yeah you know so i think anything should be on the table
|
| 01:15:01
|
it's hard to make predictions it's very easy to poke holes in these things
|
| 01:15:04
|
and more often predictions are wrong rather than right but i can tell you that i firmly believe
|
| 01:15:11
|
that anyone who says that there is a biological limit is wrong because there are plenty of
|
| 01:15:16
|
species and not just trees and not just jellyfish there are there are warm-blooded milk-giving
|
| 01:15:23
|
animals in the ocean called whales that can live hundreds of years way you know three times longer
|
| 01:15:28
|
than us they're not that different from us genetically they've figured out how to stabilize
|
| 01:15:33
|
their genome and repair their dna and all the stuff you need if we can learn from them i think
|
| 01:15:39
|
we can live a life like that and i i think historians will look back at the past 20 years
|
| 01:15:44
|
as the turning point when we realized that this was possible and finally focused our energy on the
|
| 01:15:49
|
topic so you are the world expert in the sirtuins and having made the association between resveratrol
|
| 01:15:57
|
and other small molecules and i'm wondering i think your lab is working on these small molecule
|
| 01:16:03
|
derivatives of resveratrol and other ones that activate sirtuins far more effectively so can you
|
| 01:16:11
|
comment on any ones that are in testing or close to commercial production now that might be you
|
| 01:16:17
|
know orders of magnitude better right so there are a couple of things we're doing in my lab still
|
| 01:16:25
|
on this topic that's not widely known but i'll share with everybody one is the the question of
|
| 01:16:33
|
what is resveratrol really doing you know we came out with the bold uh hypothesis that resveratrol
|
| 01:16:39
|
works through sirtuins in yeast cells and that's how it was working that was very controversial
|
| 01:16:45
|
it was a shock that you could actually activate an enzyme it was a shock that you could use one
|
| 01:16:49
|
molecule a quote-unquote dirty molecule to target very specifically one enzyme and i've basically
|
| 01:16:56
|
spent the last decade uh testing that hypothesis time and time again and we have new research that
|
| 01:17:03
|
builds upon a science paper that we had in 2013 that said that yes resveratrol is truly acting
|
| 01:17:08
|
on this enzyme we now have mice that we've engineered so that they are resistant to the
|
| 01:17:14
|
effects of resveratrol on the enzyme and those results look really promising the question is
|
| 01:17:20
|
does resveratrol still work if you block its ability to activate the sirt1 enzyme and the
|
| 01:17:26
|
answer looks like uh preliminarily yes so that that's good so the science really solid and i
|
| 01:17:32
|
wanted to to let everybody know that that's that we're still working on the science on the drug
|
| 01:17:37
|
side uh so certerus was a company that i co-founded in 2005 and it was my first company it was a
|
| 01:17:44
|
venture ventureback company it went public and it was eventually sold to glexo smith klein um for a
|
| 01:17:50
|
lot of money i i was you know a child uh got what's called diluted down to you know almost nothing
|
| 01:18:01
|
or loss yeah um you know but the little money i made has been reinvested into
|
| 01:18:07
|
new companies which i'm i'm excited about you know but but what did that teach me it taught me that
|
| 01:18:14
|
if you let go of your work early uh it's very hard to have champion and so that work it went well but
|
| 01:18:21
|
it's still not in the clinic i'll update you on that so that we made and the company made 14 000
|
| 01:18:29
|
different activators of cert1 that were up to 10 000 times more potent than resveratrol
|
| 01:18:36
|
those molecules some of them two of them went into mice uh and rafa to cover rafael to cover NIH
|
| 01:18:43
|
he put those into mice and they they lived longer it's it's quite an a poorly recognized finding
|
| 01:18:50
|
uh but it was very clear they lived longer even on a normal diet not just
|
| 01:18:54
|
high fat fat mice um one of those molecules called 2104 srt 2104
|
| 01:19:03
|
look great it went into a study in humans actually it was a pill given to patients with psoriasis
|
| 01:19:09
|
plot type psoriasis in a small study i believe it was uh somewhere between 20 and 40 patients
|
| 01:19:16
|
uh phase 2a and uh it looked really promising when the drug got into the body there was a
|
| 01:19:23
|
very significant effect on the group on the disease um so glexo uh still has those molecules
|
| 01:19:30
|
and i'm not sure what their plans are for those molecules but uh you can bet that i'll do
|
| 01:19:36
|
everything uh in my power to make sure that they make it to patients if humanly possible
|
| 01:19:43
|
we are working actually now on derivatives of the nmn molecule and any precursors and so those are
|
| 01:19:50
|
exciting as well because they can boost the levels of all seven of the sirtuins not just
|
| 01:19:55
|
number one and that's where my efforts are currently focused do they actually boost the
|
| 01:20:01
|
sirtuin levels or they just make them work better uh mostly mostly it's it's making them more active
|
| 01:20:08
|
because it's providing the co-substrate for their reaction right yep and you know gsk uh didn't they
|
| 01:20:17
|
shut down that lab that they bought from your your company in 2013 and if they did do you think it was
|
| 01:20:24
|
related to the fact that they didn't understand the importance of nad and if they were testing
|
| 01:20:28
|
aged rats or mice it's not going to work that well unless they do something to augment the nad
|
| 01:20:35
|
uh well they had a little nad program but mostly they were working on those um
|
| 01:20:39
|
direct activators coming out of the resume which will work um what i think they they didn't appreciate
|
| 01:20:48
|
was the um the wide scope of these molecules um that they're they were truly applicable
|
| 01:20:58
|
the other thing um joe that wasn't helpful to anybody uh you know in full defense of of glaxo
|
| 01:21:04
|
who are a very smart bunch of people they bought the company right as the controversy around the
|
| 01:21:11
|
mechanism blew up and it was pfizer whose scientists published that this was wrong now you know all the
|
| 01:21:18
|
trouble has died down now and we've i think proven without a doubt that we were right but in that in
|
| 01:21:24
|
those you know years of doubt it was very hard for glaxo to keep investing the tens of dollars it
|
| 01:21:30
|
was taking to go uh into larger studies um and so i think that was the biggest damage that they did
|
| 01:21:38
|
uh it was actually pfizer that that caused that controversy with one publication and you know it's
|
| 01:21:44
|
in in hindsight now it's it's really remarkable what one study can do to a whole field absolutely
|
| 01:21:53
|
absolutely so are your nmn uh derivatives getting close to commercialization yeah they're pretty
|
| 01:22:00
|
advanced um i don't talk about them a lot um mainly because we're we're not venture-packed
|
| 01:22:05
|
so we don't need to promote it we're privately funded for now but i'll give i'll give everybody
|
| 01:22:11
|
a bit of a sneak preview i talk a lot more about it in the book um we're in humans we are doing
|
| 01:22:17
|
human clinical trials we've finished two studies at harvard medical school this is not not my study
|
| 01:22:23
|
even though it's at harvard it's at the hospital nearby of course it's arm's length from me because
|
| 01:22:29
|
i i at least have the perception of a conflict of interest so i'm not involved but those two
|
| 01:22:34
|
studies have gone well uh no indicators that there's any trouble and so we're hoping to be
|
| 01:22:40
|
able to have a phase two study at least one possibly to begin um two studies beginning later
|
| 01:22:45
|
this year and early next in actually in rare diseases not in um in aging itself not yet and
|
| 01:22:52
|
so actually that you reminded me to say something that's often asked of me which is why not go treat
|
| 01:22:59
|
aging yeah we go ahead tell us why i know why but it's not a very good business plan can you imagine
|
| 01:23:06
|
the amount of money that would take to do a trial like that not only would it be expensive but at
|
| 01:23:11
|
the end of it you couldn't sell a medicine if you tried because there is no disease called aging
|
| 01:23:16
|
right now i mean there is a disease called aging you can look at it in the mirror if you want
|
| 01:23:22
|
but in terms of regulation it's not recognized yet yeah the the strategy it seems to me especially to
|
| 01:23:30
|
obtain funding is to figure out an anti-aging strategy that does marvelous things cosmetically
|
| 01:23:36
|
because the market for cosmetics is through the roof and if you have something that's effective
|
| 01:23:40
|
you'll explode in revenues and you can use those revenues to support the real thing that's going to
|
| 01:23:44
|
reverse aging well that's true and that's partly what lenny guarantee and his team and at least him
|
| 01:23:51
|
are doing they've gone to the market first i'm taking probably just as hard if not more difficult
|
| 01:23:58
|
route which is to be able to raise enough money to to get to pharmaceuticals which is
|
| 01:24:04
|
um you know a lot of money it's in the hundreds of millions but i think that's the part that i i
|
| 01:24:09
|
think is is a better one for me personally and for the for ultimately the product but yeah you're
|
| 01:24:14
|
right it's a challenge you've got to either get on the market early with something that's not well
|
| 01:24:19
|
proven or raise the money and wait five to seven years with something that is eventually proven but
|
| 01:24:26
|
neither of those is an easy path no no but most good things in life aren't it's true and this is
|
| 01:24:33
|
the big one now if you talk about what what's going to plague our planet and our humanity
|
| 01:24:38
|
our society clearly global warming energy crisis these are obvious ones but what most people don't
|
| 01:24:44
|
realize is that the future prosperity of the planet is going to depend on our ability to keep
|
| 01:24:48
|
our populations healthy for longer in terms of productivity and and cost in health care and
|
| 01:24:54
|
instead of doing whack-a-mole medicine where we treat one disease often too late to actually have
|
| 01:24:59
|
a benefit um the approach really should be one where we're treating the cause of most diseases
|
| 01:25:06
|
that will kill us which is aging itself and the idea of treating aging um was fantasy even 20 years
|
| 01:25:14
|
ago but as i hope uh you and your viewers are actually appreciating now the science is top
|
| 01:25:20
|
notch we we and my colleagues we publish in the world's best journals there'd be noble prizes on
|
| 01:25:24
|
this the time is now to be able to translate these discoveries into medicines that can
|
| 01:25:31
|
have the best chance of giving future generations even our own a chance of not being dragged down
|
| 01:25:37
|
economically by the burden of dementia and um alzheimer's is a huge one but just in general
|
| 01:25:43
|
frailty it sucks trillion dollars out of our economies yeah frayota is a big one well um my
|
| 01:25:51
|
want to extend my deepest appreciation and gratitude for all the work you've done and
|
| 01:25:56
|
are going to do because you're still a very young man the motivations for your work and your book
|
| 01:26:01
|
uh lifespan the revolutionary science of why we age is genuine and pure as far as i can determine
|
| 01:26:08
|
and you describe it in your book and your discussions with your grandmother and your
|
| 01:26:12
|
understanding of death at a very early age four years old so um you're doing a big thing to change
|
| 01:26:19
|
the world and i and uh at a level that is quite extraordinary and i deeply appreciate what you've
|
| 01:26:25
|
done and would encourage people to get the book if this is a is a topic that interests them and i
|
| 01:26:30
|
think it should interest most of us because it's not just about living law almost this that you
|
| 01:26:35
|
know who wants to live long if you said it so so eloquently is the frailty this is without frailty
|
| 01:26:39
|
obtaining the all the capacities and capabilities and certainly the mental ones that we have as a
|
| 01:26:46
|
younger individual into into older age right well yeah thanks joe appreciate it i hope people who
|
| 01:26:54
|
read the book come away with a new view of what's possible and some people who have read it tell me
|
| 01:27:00
|
that it's changed the way they look at their own lives and that's what what i wanted to do is because
|
| 01:27:05
|
i think we we forget how important this topic is that we can do things right now to to alter the
|
| 01:27:11
|
course of our lives but also just the way you think about aging itself it's not something that
|
| 01:27:18
|
uh we used to think about the way we used to think cancer and heart disease were diseases we
|
| 01:27:24
|
couldn't treat aging is is the frontier of medicine and i talk about what we can do now
|
| 01:27:32
|
and what to do in the future i also uh want to say joe i want to commend you for for doing
|
| 01:27:37
|
what you do um you know i could rant on i've been the victim uh of of some really bad uh
|
| 01:27:46
|
press mostly and it's not so negative but more it's it's hype and exaggeration uh things taken
|
| 01:27:52
|
out of context and you know that happens a lot in print media and i think that's just the nature of
|
| 01:27:57
|
the beast and you know reporters that's what they're paid to do but these these podcasts and
|
| 01:28:03
|
these venues uh i mean god bless them they're a venue for a scientist to be able to be unfiltered
|
| 01:28:11
|
and talk in depth about topics that people are really interested in and you know i think
|
| 01:28:16
|
of one thing uh that social media and youtube and these podcasts have done it's it's allowed people
|
| 01:28:22
|
to have greater understanding in depth and direct access to scientists like me which
|
| 01:28:27
|
could never be done before yeah you cannot get this information on the conventional media
|
| 01:28:32
|
the best you could hope for it a big spot would be maybe five maybe possibly 10 minutes although i
|
| 01:28:38
|
guess some of the interviews it's very rare although like you're never going to get two or
|
| 01:28:42
|
three hours like you did with joe rogan and your joe rogan podcast and others so i thank you for
|
| 01:28:47
|
being so gracious i know you're a busy man and really for taking the time to really dive deep
|
| 01:28:53
|
and i think you've done a magnificent job in this interview because uh you know you share stuff that
|
| 01:28:57
|
i really haven't heard you talk about previously so thank you for doing that thanks joe thanks
|
| 01:29:00
|
for having me on okay
|
