Welcome to the Life Span podcast where we discuss the science of aging and how to be healthier at any stage of life.
I'm David Sinclair. I'm a professor at Harvard Medical School and co-director of the Polish. Glenn Center for aging research. And I'm joined today by my lovely, co-author and co-host. Matthew Laplante. Hey, hey, we feel great again. We are. We're here today to talk about how to live longer and better
as part of this podcast series. The yeah. This arrived in the things that you can do to slow stop and reverse aging
that is true. And today is going to be a really interesting one.
This is
Be the one that everybody. I mean, this is the one that everybody's been begging
for that is true. We've been monitoring the responses to tweets and Instagram posts and most of them are David. Just tell us what to
take the nice ones. Yeah, some of those aren't very nice either. But yeah, who please please, please. Should I take n r, should I take n MN? What should I do with metformin? We're going to be talking about all that. Today.
We are in our research team has been spending weeks on this and if you can see, I'm actually sitting in
front of many pages of notes here. We're going to go deep dive into what is fact and what is not fact, what is known, what is not known? Because there's so much misinformation out there, especially with supplements. Yeah.
We do need to say, we usually take a moment to thank our sponsors. We're going to do that, of course, but we also have to take a moment to say we are not medical doctors. We are not medical doctors. We are not medical.
Doctors what he said. I'm a PhD. I'm a researcher. I can read the literature. I've been doing it for the last 30 years.
I distilled that for everybody, but, of course, if you want to try supplement or even change your diet, radically, please talk to your physician before you change anything because some of the things we'll talk about today, can affect your body in, hopefully many good ways, but sometimes can be dangerous, depending on the person and everybody's
different and what we want to do is give people the ability to have a more intelligent and informed conversation with their physician, exactly? Okay. With that out of the way, now we should thank our
Answers, let's do that because this podcast is free, Tony. Anybody who wants to watch or listen. Our first sponsor is levels. Levels is an app that syncs with A continuous glucose monitor, which they provide and it interprets, your glucose data for you. I've been so impressed by levels that I've recently joined them as an advisor monitoring. Your blood glucose allows you to see how different foods impact you. I've used levels to see what foods impact me. I've learned that grape Spike, my glucose white rice, but actually potatoes aren't that bad.
It's not just interesting. It's also a lot of fun to see what's going on inside your body. So if you'd like to try levels you can skip the 150,000 person. Waitlist. You can join today by going to levels dot link / Sinclair that's levels dot link. / Sinclair. Today's podcast is also brought To Us by inside tracker inside tracker is a personalized nutrition platform that analyzes data from your blood and DNA tell you better understand your body and reach your health goals. I've been using inside tracker for over a decade and also serve
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And you'll get 25% off. Every inside track of plan. You Sinclair as the code at the checkout. Today's episode is also brought To Us by athletic greens, the all-in-one daily drink to support Better Health and Peak Performance. Athletic greens is a greens powder developed from a complex blend of 75 vitamins, minerals, and Whole Food, sourced ingredients. It's filled with adaptogens for Recovery probiotics, and digestive enzymes for gut health, as well as vitamin C and zinc, citrate for immune support.
I've been drinking athletic Greens in the morning for many years and I do that because I don't often eat perfectly and I travel a lot and I can rest assured that I'm getting all the nutrients I need for Optimal Health. So if you'd like to try athletic greens, you can go to athletic greens.com, / Sinclair, to claim a special offer. They're giving away 5 free travel packs. Plus a year's supply of vitamin D3 for immune support and vitamin K2 for keeping calcium, out of your arteries and putting it where it's needed in.
Bones, again, go to athletic greens.com Sinclair, to claim this special offer. Okay, Matt, let's dive in, there's a lot to get through today. And I know everyone's waiting to hear what we have to say today
in the last episode. David. We talked about adversity memetics. These are the things that we can do in our modern lives to mirror the sort of stresses. We faced across our evolutionary history, but even if you're engaged in doing these things like we've talked about already fasting gets you
A lots of exercise getting out of your comfort zone. Our modern lives are still designed around comfort and sedentary Miss sedentary, that'll work sedentary lifestyle sedentary Lifestyles and that's not to mention the fact that even before modern times we aged right? So if we're going to combat aging, we may need an additional boost you believe, we may need an additional boost.
Well, I do and I've been doing this since my early 30s will talk about my program at the end.
This episode. But really what we want to do today is to talk about some of the major supplements and medicines that are thought and have the greatest scientific evidence to be able to give you Wellness. Now, as well as long-term Health in the
future, supplements and medicines drugs, and supplements molecules, and drugs are a lot of different terms that were probably going to throw around and we're going to use them fairly synonymously, but In fairness, let's, let's define drug versus supplement at least
right? Well, first of all,
Most drugs are chemicals. Okay, but some are naturally occurring in some are freely available over-the-counter OTC and that's because they've been in our food supply before and the FDA doesn't regulate them. They fall under what's called generally recognized as safe or grass and that's why you can, you can pick up a whole variety of molecules from the Plant World because they're already enough food supply. Therefore, the government thinks. Well, the probably okay, even if there are a thousand times more concentrated things that you're eating but you
which may or may not be the case.
Right. And so that's why you always have to be careful. You have to monitor yourself. Like, I have been with my blood work for many years to make sure that you're not hurting parts of your body. Your liver, particularly could be sensitive to some of these molecules, even if they are available freely at the pharmacy, or the Vitamin Shoppe different story about drugs, drugs are regulated molecules because they have the chance to actually cause damage and many drugs actually do have serious side effects that need to be carefully monitored and discussed with a doctor.
Even those that are very safe. Like, we'll talk about metformin. These are regulated by the government because they are not in the food supply, their artificial molecules, that could theoretically do
damage and there are literally thousands of drugs and supplements that someone somewhere will tell you will help you with health plans and lungs. But lifespans we're not going to talk about thousands of drugs and supplements today
know maybe in future episodes. We'll come back but we want to hit the high points
today. And so that's why today we're going to move through some of the most popular and
The most promising, these are things that most people can have access to or find a physician who if the need exists will prescribe
right? And I get emails and I get all sorts of texts every day. DM's. What should I take? What about this? What about that? What's the dose? When should I take it? What should I take it with? Is it okay to take this drug with exercise or not? That's what we're going to cover today. Your most pressing questions answered here today.
And so, we're going to talk about NAD. Boosters will talk about metformin. Berberine rapamycin spermidine Resveratrol finds it in a sit-in and probably a few others, but those are sort of the Highlight points. If you're only interested in one of these, or if you watch this whole episode, need a reminder, the show notes are going to be timestamp. So you can immediately go to berberine and find it and click on
it. That's right. Included in the show. Notes of the scientific references that we now have in front of us. We're going to talk.
About so that people can do a deep dive even deeper than what we're going to do here today.
There's one more thing that will link to in the show notes that's on your website that I think is valuable to for people to know about your involved in a lot of different companies. You're an entrepreneur, you're a researcher. You have. I don't know how many patents there are plenty of people would say. Oh, this guy's just trying to sell stuff. If they suspect that you might have a conflict of interest, they can go and look at your
disclosures.
I do disclose everything that I do. My lab has a website, you can Google Sinclair lab and if you click through my bio, there's a link to all the work that I do outside of Harvard as well as what we do at Harvard, of course, but importantly, I've never sold any supplement in my lifetime and
that's not because you're a bad salesman. It's because you haven't actually tried to sell. I mean, there's a difference between having not sold to supplement and having tried to sell a supplement and not sold this
up. Alright, I've actively kept myself away from supplement industry because I want to be able to talk about
Things without any
bias, not for lack of opportunity though. There's plenty of people who would love to put your face on a
package. Well, and they do without my permission, you can see my face on the internet. But if you see that know that, it's not worth, not with my permission and I do actively try to stop
that to get into this. Let's use some of the same framing that we've used for the other conversation. And that's these three longevity Pathways three longevity genes that we've been talking about sirtuins ampk and mtor, different drugs and supplements, or thought to work on.
These different Pathways in different ways and we'll sort of like categorize them in those three buckets
today. Exactly. And the thing to also remember is that these three survival Pathways we've talked about and in episode 1, we talked a lot about are responding to our environment with your exercising or fasting. They'll turn on but also appreciate that. They talk to each other and some drugs or supplements will activate one of these and talk to the other two. So it's, it's a network and we're still trying to figure out exactly what the optimal combination for each individual might be whether to tweak
This molecule and then exercise here and then fast that day. We don't know all the answers but we are going to present The Cutting Edge science here
today. Well, and I think it's been really interesting. I've been working with you for what like about four years now and in that time, a lot of the molecules that we knew to be working on one of these Pathways, there's been further research that have said, oh, that's not just an ampk effect. There's also an mtor connection there.
Well, they definitely talk to each other and because if you're low on amino acids and it
It'll turn on the mtor protection pathway that will then tell the other survival Pathways to do their thing, too. It's like the Pentagon where there's centrally coordinated defenses. And basically what I try to do is to make a prank phone call to the Pentagon to say if there's an emergency and I'll send out the troops in various ways and protect the body even though there's no immediate threat. I like that analogy. That's fun.
Let's talk about the class of molecules that you've worked.
Extensively on in your lab. These are known as NAD. Boosters talk a little bit about how why NAD is important in our bodies. It's really important. We if it disappears we're screwed, right?
Well, we be dead in 30 seconds. We need it for energy and but it was discovered about a hundred years ago by Germans were looking at extracting yeast and there was this component called NAD that was necessary for chemical reaction
and we didn't say what that sounds for. That's
so NAD stands for Nikki.
It's an amide, which is vitamin B3 and adenine dinucleotide. This is a sugar and a phosphate, the important part about it is that the cells are cells, use NAD to transfer hydrogen atoms between proteins and even DNA, that is really important for life. And without it we can't make chemical energy, which is in the form of ATP, which we'll talk about later because that's important for metformin. Any D is found in abundance. There's many grams of it in the body. It's probably with the exception of ATP, the most abundant.
Do we have in the body? It helps us make energy but it also has this other function. That's just as important that we worked on and just co-discovered in the 2000s. It activates the sirtuins and the sort of tunes of these defensive enzymes that like a pentagon. Send out the troops. The problem is as we get older, we make less NAD and we also destroy it. More for reasons that we don't fully understand but it leads to a decline in our ability to fight off aging and the diseases that it
causes and this is because any D is
A sensor for adversity.
It is if you exercise, it's known and fast, it's known to raise NAD levels, but even though even if you exercise and have the healthiest diet, you're still going to have lower energy levels by the time, you're in the latter half of your life. So that's why these supplements are thought to help because they'll boost up those older levels of NAD to where they were when you were
young. Okay. So, let's talk about the first NAD. Booster probably the most well-known. It's definitely the most. Well, studied.
Of the NAD boosters, and probably the most taken used that sin R
which stands for nicotinamide, right beside. So, that's the vitamin B3 plus the sugar without the Empire, which is a phosphate will get to the phosphate that's important later. It may make a difference but in our has been taken over the counter or through websites for what since 2014, either solely just as a capsule or there's some companies that sell it in combination with
Other molecules
and because it has been pretty well studied in humans. There have been plenty of human studies at least in the short term that show little to no side effects. This is a pretty safe molecule.
That's for sure. And we know that if you take it as a supplement, just swallow the pill, either 250 milligrams per day or a gram. There's no power negative side effects. And in fact, you will raise any D levels in blood
test. So, I think this is
Important distinction to make though, like there's a difference between safe and effective, right? Just because we say something is safe, doesn't mean it's going to work in it. And in fact, sometimes things that are the most safe are going to work at all. That's why they're so safe. Is they don't have any effect, but we do know that an R is largely safe, you know, millions of people around the world, take it and art has been well studied in animals as well. And let's start with that because we actually know more about what NR does in the bodies of animals that we do in the bodies of humans, but let's
start with yeast.
Go even further back. Okay. Yeah, so that's where it was supposed to scuppered and our was a newly, discovered molecule back in the early 2000s, found a little bit in milk and other foodstuffs and if it was fed to yeast, they lived longer by turning on the yeasts or two and
pathway. Okay, how much longer would the
living? Generally, the East live about 30% longer when you give them, these molecules similar to caloric restriction. And that's what this was doing mimicking caloric restriction because both activate the sirtuins and give increased genome.
Ability and Epi genome instability that were lengthens their
life and those kinds of findings, make you really interested because you're really interested is sirtuin activation. And so you've been part of a group of scientists that have been looking at
this. Yeah, one of the first things that we discovered this is now attacking 2002-2003 in my lab is that there's an NAD synthesis Jane called PNC. One in our body. It's called MPT, and it gets activated by these mild stresses in a yeast Cell. It's low salt, it's low sugar.
Heat and that turns on the synthesis of NAD and we found that extended lifespan and then a few years later. It was shown that you can mimic this effect with this NR. How does the
NR turn into
NAD? So NR has to go through an intermediate molecule. Let's start with the mouth you swallow your in our, it'll go into the gut. Some of it will be metabolized by the gut bacteria, but it will most of it will go into the bloodstream and then flow around and then get taken up into your muscle into your brain and other cells. That
By transport is called EMTs. And there, it's converted into n MN by what are called in our case, and then you add the phosphate and have got this thing nmn, what? Cinnamon, nicotinamide mono nucleotide, and then the cell puts two of those together to make any
D. And when we do this in laboratory animals, you mentioned in yeast, it extends Life by 30%. What have we seen in mice? Which were a little closer to you? And I, the new yeast
is
Yeah, it's going back a number of years ago. It was found that NR when given two mice extends the lifespan by about 9%, but it was given to them late in life at about 700 days, which is pretty Old Masters. Been like a 70 year old human, but it still worked but there were also improvements in health. They had more mitochondria, which is the energy, they had more athleticism, less inflammation. And so that was the first real study. That said, okay, maybe supplementing with these molecules like an r or nmn might have some long-term.
Benefits as well. And humans
among the other health benefits that have been seen by researchers, who have given an R2 animals in the lab. Enhanced oxidative
metabolism. Let's talk to that. Burn more fat. Yeah, they get thinner. And that also means that they've been in more oxygen and that's thought to be really good at staving off, Diabetes Type 2 diabetes, as well as improving life span.
Let's carry this now under the human studies because what we don't have for
Reasons that maybe are obvious, but I'm going to say it anyway, which is it humans live a very long life and it's really hard to put humans into a control group and a test group across a very long time. Then control for every variable, that's possible is longitudinal studies that show increases in life span as a result of taking and our, but we do have studies that have sought to show similar health benefits to what we've seen in
rodents.
Some what I would say an our they've been a few positive results, not a lot before we get to that. I think it's worth talking about. Why can't we just take vitamin B3 which is a precursor to NR and you can but it doesn't raise any D levels, anywhere near the level that NR does and in our doesn't seem to be as effective as nmn. So the closer you get to NAD with your molecule, the better, it seems and that's probably because you need to bring in other components. So if you just take vitamin B3,
Sugar and the phosphate if you just take an hour, you need the phosphate and phosphate is pretty rare in the body. You it's in your bones. It's in your DNA. And maybe when you take in, are one of the issues is that you need to find the phosphate at on there before it becomes active. Okay? Back
to the human studies on an
R.
We have sought to Zero by we, I mean, the research Community. I mean, necessarily you and me. We've sought to see the same.
Sorts of effects that have been seen in models
organism studies
some times that's happened. Sometimes it is not is that fair to say
that's very fair to say with n? Are there have been a handful of studies in humans showing that low dose, 250 milligrams per day up to a pretty large dose of grammar. Day does raise any D levels, but it takes about 9 to 10 days to get to those Peak levels.
What we've also seen is or others have seen is lower inflammation as well as some other markers such as minor changes in body composition, but these other things which are low blood sugar improvements in insulin sensitivity, increase mitochondria. Those haven't been borne out just yet in these short-term studies within are not
viewed. Sorry. These are the things that were present in the mice who also lived
longer, right? Yeah. Now it could be that you need a
The term exposure of these people. These have been fairly short term studies or that humans are not the same as my
eyes. So would you say I mean, if somebody said tells, you all David, I've been taking an arm for so many times. You're not rolling your eyes, but you're not convinced at this point. The the jury's still out.
Well, it depends what you're asking. If it's to lower inflammation. Yeah, it probably works. There's also a study that was put out by a group that combined NR with Tara still being which is a Resveratrol like my
Luckily, we'll talk about Resveratrol next. That found that in ALS patients, Lou Gehrig's Disease. There was an improvement in their function daily function. So that that is somewhat promising. I think that we, of course, we need more studies. That's what we really need here to be able to make any sort of conclusion about what the long-term effects of taking this supplement. Our,
it's fair to say that in the sir to inactivate, a compound research Community. There's kind of team and our and then there's team nmn, your
Lab really focuses on and MN. And I think if people were sort of like following what you said earlier about, how an R turns into NAD, they might go. Oh, well, and our turns into mnmn turns into NAD. So, why don't we just take nmn to begin with anyway? And you'd mentioned earlier, phosphate and that's what that's an important component of this. This
question. Well, it is in our is more popular because it's cheaper to make. It's doesn't have that.
Spike which can be expensive to put on the molecule Through Chemistry and that's why most people started using in our first in humans. And in Mouse experiments. I didn't have a horse in the race. I didn't care which one in fact, I'd prefer if both worked according to you know, my theories, but it what we found through empirical studies. Basically, we're looking at which one's work better, my lab and others including Mac cable line, whose at Wash U who treated a mitochondrial disorder and we were trading. Regular - on treadmills, we found that enemies.
Has worked better at the same dose. We don't actually understand why it could be that. This phosphate addition is one of the reasons but, you know just based on observations in our hands and in others, and a man works better than NR
when we supplement with nmn when when NM n is given to organisms in the lab. What's
happening? Well, it's a little different. There's been an argument in the literature that nmn doesn't get into cells. And similarly NAD is really a big molecule because it's got multiple components.
And that also has a real struggle to get it into cells neurons, take it off, but other cells, typically need to break it down into its various components and then reuptake it and that's important because some people actually are giving themselves NAD through the IV route. When it comes to enter man. What happens is it was recently discovered by Shin Mi at Wash U. His team discovered that there's a specific transporter that takes an immense out of the liquid outside the cells inside the cell and its name is SLC 12-8.
A still debated, a lot of things to figure out, but I think it's just best to say, okay. We know what's happening, when you give it to animals. We're starting to learn happens to people. Of course, want to understand how it's working. But the fact that it does work is the most important
point. So, when it comes to MMM, there's been a number of animal studies showing for instance, similar to and our restores NAD levels. It enhances insulin sensitivity. One of the things that was
Using to me is that we don't have a study that shows and an immense effect across analysis entire lifespan yet.
Yeah. Well, we have half a life span Sheena. My showed that it actually was pretty good at slowing down the effects of Aging but he stopped the experiment because he ran out of nmn. The used to be rare stuff. Now you can buy it but we took up the challenge and we've been doing these studies for the last few years in my life. Now Plumbing narrowly these mice, have less Frailty. We've reported that
out in the scientific Community. They seem to be younger. Having better activity, better mitochondrial function. They run further. The lifespan looks promising. We've done it once and they do live longer on. Enderman. The dose was about, 400 makes per kick. How much longer at this point by Recollections, about 10 to 15 percent, but particularly strong in females.
Okay, so not not particularly it like, like wholly different than what we saw in the end. Our cases with the mice,
right? A little bit better than that, but certainly the
Those mice are healthier and more active and more youthful. And
he said, it's more pronounced than the females, or at least, according to the first phase of this. It's more pronounced than the
females. Right? Well, we had fewer females, so we have to repeat that. So, we've now got a larger cohort of mice, were repeating a whole thing. We'll see how it goes. But right now, with the small number of females yet. They did do better than them.
And what even though? Mice live, pretty short lives. What we have to understand here is that there's still live 23 years on average, right? And so on.
In order to see lifespan extension, especially if they live much longer it takes some time to do these studies.
Yeah, it's quite painful. Actually because you think about this and average experiment takes three years and then you have to repeat it. So that's now six years then to analyze the data and publish. It is another three or four. That's a decade's worth of work for one experiment and you career, only goes for about five of those times. So, you'd five experiments because you can roll them to the South
Koreans used to go. We're going to
Is that
right? We're going to live a lot longer, we run things in parallel as well. That's important, but we can also mimic things. Not just in animals, but we're growing tissues in. The dish will be the subject of a later
episode. Okay. So, so, so far, what I'm hearing is in animals and our and mmin both have some similar effects, right? Lengthening lifespan restoring mitochondrial activity restoring NAD levels, enhancing, insulin, sensitivity.
T. But in NR the human studies haven't always confirmed that. That's the exact same thing that's happening in humans. What are we seeing in the human studies for
nmn? I know a fair bit about the effect of NAD boosters in humans because I'm helping a group that is actually doing clinical trials, at Harvard Medical School and they've been giving a molecule that's similar to nmn, two subjects for many years. Now. First of all, there's importantly, there's been no evidence of any negative side effects, that's important, and we're about to learn
Whether it actually does anything, that's similar to the mice, we don't have results in yet. But hopefully by 2022 will actually know if people have more energy more mitochondria function, better blood flow more endurance, which is what we saw in those
mice. There's a little bit, less human research on nmn than in an R. But we're starting to see just in the last couple of years, especially sort of a flood of studies being published early results, for instance, from Yoshino at all in
21 showed increased insulin, stimulated glucose disposal. We talked about this a little bit. When this study came out, you were pretty excited about it. Tell me why
it's one of the first real proofs that nmn does something in humans the way it works in mice. So this was a 10-week study. It's well done. It's randomized placebo-controlled. It was 250 mg, which is a relatively low dose. Remember I'm taking in. My clinical trials are a g + 2. G is 250 milligrams. Nevertheless it improved what?
You said, insulin stimulated glucose disposal? Let's basically insulin sensitivity. And that's a Hallmark of longevity. Keeping the glucose out of the bloodstream. Keeping it low levels is a Hallmark of wellness and ultimately longer life. So that's the beginning. But we have a lot more to figure out. We need to figure out if that increased endurance that we see in my lab within a man treated mice is true for humans. We also want to know our organs protected, other labs, not mine, but other labs have shown that nmn protects the organs when they're damaged kidney and heart the two main ones.
I'll even increased wound healing. We I'd love to know if any man does that in humans out to be a big deal. Kidney injury is huge in particular. I don't know if you know this but most surgeries on the heart end up, damaging the kidneys and there's not much you can do about it. So ultimately we've seen a glimpse with Yoshino. I do my studies that I'm involved with at Harvard. Medical School are looking promising. We'll know more next year. But yeah, there's a lot more in the in the works and there are other NAD boosting molecules that have been made.
There are even better than any man. So called nces called new chemical entities and those I'm aware of probably in the next year. We'll go into the first human
studies and as I mean that can be in a whole episode of this podcast in and of itself. Yeah, we should do it. Yeah. Okay. Why
don't we
just give NAD directly to talk about like NAD boosters and our boots and our creates a Time n. And a man creates NAD that boasts. It boosts NAD or mmm, boost NAD, but it all gets us to a
NAD. So why don't we just, you know, set up the drip line and get it
going, but we don't, but others do. There's a lot of activity going on in Florida, and l.a. Particularly of having large drips, long drips of over an hour of
NAD. These are not to Grant. These are not in study settings. This is not in a research setting. This is a like people trying this
out. Well, they don't under medical supervision. Uh-huh, but I haven't yet seen a placebo controlled trial. That would tell us for sure, if it's
Just wishful thinking or not. I don't think so. Given how many people have been now treated as a serious amount of anecdotal data on this better, mood, better energy. But, you know, you cannot conclude anything. Unless you actually have one of these placebo-controlled trials. I'd love to be involved. If anybody's going to do one. I'd love to help. But I'm asked this probably every day NAD, IVs do, they work? My aunt's have to has to be, we don't know
yet. What do we think? They might be going? What are people trying
them for?
Well, they used for various things. It's been used for many years to treat addiction. Whether it's drugs or alcohol. It's also used for depression and also increasingly for hangovers. Is that as good
as the Australian hangover cure, that you've given me a few times
all the the raw egg in the Vegemite. Yeah. I hope it's better than that but the idea because the
truth is that doesn't work. I just pretend it works because it makes you
happy. That's true. And you're one of the few people that eats my Vegemite, but the reason that it
Only works is there's an enzyme that detoxifies alcohol called alcohol dehydrogenase. And a lot of Asians are susceptible to high levels of alcohol, because they lack a lot of this enzyme alcohol, dehydrogenase needs NAD. And so, what's probably happening is, when you wake up with a hangover you lack, any D. Your liver is depleted, you. And if you take in a mentor in our, you can raise those levels. Back up, get your liver working again and get rid of the excess alcohol.
So you think chances are that is
Is actually, it's not just like a placebo effect that there's a chance that, like, it makes sense, that, that would work.
I think make sense is the right word to use. You know, I'm a Harvard Professor. I'm not going to say something works. Unless I've seen hardcore proof and I hope that will come in the next year or
so. It's just so I'm clear on this though, because it's still, it's still a little fuzzy to me. Like, why why we, I can understand why we might want to use NAD. I'm not understanding why we're not starting for.
Since all the research with NAD and then moving backwards to nmn and then moving backwards to
NR. Yeah. Well it all started in yeast when I was at Harvard early 2000 even in yeast if you give them NAD, it doesn't work because it's too big. It doesn't get taken up into the cells. So what we want to do is back off in size. So the next smaller molecule behind NAD is nmn. And there we know there's a transporter protein that sucks it into cells and in our is even smaller and it gets taken up even better into cells.
And so that's the reason why it may be that in a man is at The Sweet Spot of the right size, but also has the right components to make just the right amount of
NAD. This feels like a good time to talk about bioavailability and making things available to our bodies. Machinery. How do we make and our and MN? Most bioavailable,
just swallowing it is enough in our studies to raise any d, by two to threefold.
Also, if you buy the for instance, the capsules are often sold in capsules. Just swallowing, that's going to
be or the powder just
Kitt, that's weekly my tablets and give it to the patients. That way the subject but there are others. There is a sublingual version. I have heard, there's evidence that works. I haven't yet seen it. Doesn't it make sense that it would be absorbed under the tongue, or you can inject
it. But in terms of the research right now, it doesn't seem like there's a huge Advantage, One Way or
Another. No, I haven't seen any reason for saying that you need to put it under your tongue versus swallow. It, what I can say for sure is that I've seen so much data on.
In swallowing it that it definitely works to raise any D levels.
There has been some concern around the use of NAD boosters when it comes to the potential that it might stimulate cancer growth. And obviously that's something that we don't want to be dismissive of it. Does you no good to be boosting your natas and extending your lifespan. If you're just giving yourself cancer. What's the latest research on that and how concerned should
people be? Well, so most of these studies
Is actually there's only two main Studies have been done in mice. So here's what they are. There was one again, out of Washington, University by different group that found that knocking down the levels of NAD in brain, tumors slowed, the growth of the tumor. And unfortunately, the new story ended up being 0 NAD causes cancer, which is not the same. I, that's the complete opposite. So that study, I wouldn't put a lot of stock into. But there is, there is one other study that came out in 2019 by naccarelli and they found that MPT this any
Edie boosting Gene, it increases the number of senescent cells and makes them more inflammatory. Giving out these SAS proteins as they called, the senescence Associated, secretory phenotype is the word. But also there were mice that were predisposed to pancreatic cancer and when given an amen, they developed more precancerous and cancerous growths when they consumed this animation exactly how it works. Were not sure, but it might be because it was down regulating. But you must suppressor Gene called p53
and his
Is a subgroup of mice that were already predisposed. They had a gene that made them more likely to get cancer.
Right? But remember, we've fed annamund two mice, but normal mice, not predisposed. And if anything they live longer and healthier, so it's question, whether it's this predisposition. That's the difference,
something to watch for and to think about, and of work into anyone's calculations if they're going to be considering an entity booster in any
case Fisher, and another reason to consult your physician. Absolutely. Okay.
Now there are other
Other NAD boosters or two in activating compounds. One of the ones that you've been really interested in that, I think a lot of people are interested in probably really, widely used is Resveratrol. You started working with resveratrol back when you were under trying to understand sir to an activation in the
East, right? I was just a kid. I was in my early 30s and what I was I just came out of MIT with Lenny guarantee where we'd found that
Up regulating the sirtuin genes in yeast, extend their lifespan. But of course, we can't up regulate genes easily in our body working to genetically modify ourselves any time
soon. Not not any time soon
we can but we're not going to. It's easier to find a safe natural molecule that does the same thing. And so our goal back in the early 2000s at Harvard was to look for any molecule that we could find. That was safe. That would activate the protein, not the gene, but the protein, the it's an enzyme that controls all the
And remember and so we set up an essay that looks for what's called sirt1 activation sort one is the first out of seven of them in the body and Conrad, how it's my collaborator and I were using an essay in a test tube. That would fluorescent. It would fluoresce when you had more activity. And so we added these chemicals. We added a dozen. Then we added thousands and eventually tens of thousands to sort one and found which ones raise the level of
fluorescence and you found a bunch of them there like 20 of them.
It we published 20 year in nature 2003. The one that was the best at the time, which activated 13-fold. So on activity was Resveratrol and there are others. Course itself has eaten, which are actually now used by others for longevity. But Resveratrol got most of the attention because it's found in red wine.
And you've told me this bunch of times, red wine, stock went out the right, like, people started by and red wine like
crazy because it percent sales and they've stayed up ever since and I've started drinking more red wine as a result as well.
Well, but when I looked the
truth is though, how much red wine? Would you actually need to drink in order to increase your levels of Resveratrol and get an actual effect out of
this, right? You know, you can't drink enough red wine to get the kind of doses that are efficacious and you can't. Well, you can try, but I don't recommend it. You'd need hundreds of glasses of red wine a day, which I don't recommend. Even if your doctor says so. Not
recommended. That's not going to extend your
life. Probably not. No, but what you can do is you can
Terrified out of grape vines or polygon, mm, cuspid atom, which is a herbal plant. Mostly grown in
Asia. When you say that, could can you just take your pain? Take your pain? Yeah. All right. Now, say that word again and go like this when you do
it, Polly going to cuspid Atif. Okay. Thank you. I appreciate it. I joke, I think. Yeah, I Harry Potter. Yeah.
How much Resveratrol do we actually need to see an
effect? Well, there are a lot of human studies. Now, the minimum that I've seen is 250 milligrams a day and some people take 1000 or
1,000 milligrams a
day. This is a cert activator like the other NAD boosters. We've been talking about Works a little bit differently. But like you said really well studied and for almost 20 years now, what's what's happening? When we put risk Fair trial, let's start with the animal studies. What do we
know? Well, we know, first of all, if you just give it to them in their water supply it's not going to work. You can't just swallow it and expect it to get in easily. Why not? Well Resveratrol is the equivalent of brick.
It's really insoluble. If you put it in a glass of water will fall to the bottom. So what you need to do is we found in both mice and humans, mix it with some food. You can use yogurt. You can use our kind of olive oil that kind of oily food and it will dissolve. Its hydrophobic. This is the problem. It's scared of water.
And this is actually why you suggested it may be some risk, their trial studies, that have shown that it doesn't work as well as other studies show. Those studies may have involved people who are feeding my
Has Resveratrol without that additional
fat? Yeah, that's the case. Some of these studies didn't include food. We found that early on in the mid-2000s that if we gave it with a meal, the levels in the blood went way
up. There have been a number of animal studies on Resveratrol going back almost 20 years. Now. We're seeing extended replicative lifespan in yeast. We're seeing activation of a
K in rodents, what are these things telling you? Well, they're similar to
what we expected from the sirtuins. They defend the body. They raise the metabolic rate. They protect against free radicals. And when we see Resveratrol given to these rodents, what the biggest surprise was was that they were protected against a high-fat so-called Western diet, those my son Resveratrol.
Even though they were really obese on this really chunky meal, they lived as long as the lean mice that we had, is the control group. And that was really, as far as I know, the first study of any that showed that you could mimic caloric restriction with a molecule and be fat, but live as healthy as a lean animal.
Have those findings translated over as we've moved Resveratrol into human
studies. Yes somewhat. I'm not all Studies have worked but there are a number of them that have and
For instance, Resveratrol has been shown to reduce fasting glucose and significantly. Increase insulin sensitivity. This was a study in 2019. And then again in 2020 Batista and George a towel show that a randomized controlled study with 25 individuals ranging, from 30, to 60 year olds with a slightly high BMI of 30 were able to lower their cholesterol levels, their urea levels, which is important for a kidney function as well as
Raise their good cholesterol the
HDL. But once again, we don't know long-term what this is going to do, but the trajectory seems good when we consider it in the context of what we see in animals and what we are seeing in these early human
studies. Yeah, I think so even before I worked on Resveratrol it was known to be an agent that suppress cancer. If you put a carcinogen on the skin of mice and then rubbers virtual on it. 1999 science paper showed that those
Cancers a much smaller in those treated mice. So at the ANSI, anti-cancer activity of research has been known before I came along and since then we've seen effects on body, composition on metabolic rate, mitochondrial, boosting glucose levels. The list goes on. There's probably a thousand papers now showing at least the benefits in animals and a dozen in humans, cardiovascular disease. I haven't mentioned but that's a big one may help, explain the French paradox. The French can eat high fat foods and with this glass.
Two of red wine every day at it helps mitigate. The
effects does, is that Roman? Like, but you've just said, like, you actually have to drink so much red wine in order to get this effect. But then we're thinking maybe the French who don't drink that much red wine, even though they do drink a lot of red wine, but they don't drink that much red wine.
I'm there's two considerations here one, is that drinking red wine over 30 years could have a cumulative effect and it builds up in the body. And the second is that red wine has more than Resveratrol and it has some of these other Zeno hermetic.
Also, we talked about in earlier episodes, but could give a combination effect.
Okay? The to other molecules. I wanted to mention you mentioned earlier actually by name. These were part of the group of molecules that were identified in those early experiments with yeast that identified Resveratrol as a potential certain when activating compound. These are fi seden and Kirsten and both in addition to being certain activators.
He also seemed to have this other property to them, that is making them sort of like a hot number down,
right? They are what are called scent oolitic, kill senescent cells
and senescent cells,
are zombie-like cells. The ones that accumulate over time in your body probably because their epigenome gets screwed up, but what they do is they shut down. They stop dividing and they start secreting, inflammatory factors and also like factors that cause
cancer. Yeah, and so getting rid of those would be presumably a good thing and that's
If I sit in kherson and appear to
do, they do in the dish and in mice. And there are even some human studies. Now that show that killing off these senescent cells in the body, can improve health. And ultimately, we think could extend
lifespan, and these have been shown in the case of Phi, sedan atleast to extend life spans and some model
organisms, like fruit flies. Yeah, and even in mice recently, I was particularly impressed by the, the mouse studies couple of colleagues out at the
University of Minnesota are able to show that physician put in either in the food of the mouse when its young or even late in life. After 700 days, which is like a 75 year old human, was able to extend lifespan quite dramatic dramatically up to 30%, including improving their health and that's ostensibly because both its removing those senescent cells, and activating the certain defenses
and there have been human studies in both of these as well. I know, we kind of talked about these in a group because they were discovered as sirtuin activators and
Now they're being seen also as potential sin, a lytx, but maybe we can differentiate a little
well, a lot more is known about course, certain. Okay, that was discovered first as a sin, oolitic by Jim Koch alone to the Mayo Clinic who combined it with a drug called dasatinib. And together those two molecules are potent killers of senescent cells and those have been put into mice and into humans where they are showing really remarkable effects in treating age-related
diseases, and we've had some randomized controlled.
Aisles with humans and crusted in the effects
are reduces liver steatosis. A fatty liver as well as other effects like inflammation in the body. You can actually see that the number of senescent cells in the body goes away. When you treat with course certain and decide
nib. Does that nib, is a drug that's used to treat. Leukemia. It's got a lot of Promise as a set of lytic to. It seems, as of right now, you can really only get it for treatment for
leukemia. That's right.
Can only get it if you part of a clinical trial, you can't just go buy it on the Internet. It's a, it's a regulated drug as well as another drug that's analytic which is called, Nevada, collects. These are being tested. They're not ready for prime time at all. But for Satan is the interesting one, that one is a plant molecule that's found in grapes. It's found in apples high levels, relatively high levels in strawberries. You can now buy that relatively cheaply on the internet.
So if people are like man, I really like want to get into that analytics. The the Gateway right now the most important
Accessible place for people is to Seaton.
Well it is but it's early days. There's not a lot of data compared to a corset in and decide nib really? We know that it's it reduces inflammation. That's about it in humans. I think we still have to wait to see whether it's really truly safe before. People rush out and try this. I'm excited about this affirm light study by Jim: with fizz Eden. He's got a number of patients are on 20 milligrams, per kilogram of body weight. And this, over the next year.
So should tell us whether Fizz eaten is truly a sin oolitic in humans and can have some health benefits to
okay. So there is a third class of drugs. We want to talk about today. We're going to have been too much time with them because broadly speaking they're not available for purchase or even prescription right now. Except for very, very narrow instances. I'm talking about rapamycin and these drugs that are wrap a logs drugs that are supposed to mimic the effects of rapamycin. Perhaps, without all the
Toxicity. These drugs have a really interesting history.
Well, they do. These are drugs that inhibit mtor, which is mimicking fasting. They were discovered a number of years ago on Easter Islands Rapa Nui, which is why they're called. It's called rapamycin on the back of a statue. I believe somebody
found. Yeah, there's like the mold and they are some fungus and they scraped it off and lo and behold. We have a drug that actually has been used for other purposes. Immune suppression. Yeah, cancer. Like really, I mean, this is a life-saving drug.
Just don't know yet. If it's a life-extending drug, that's going to be useful in
humans. Well, I put good money on it. The reason is that it's extended the lifespan of every organism. It's been given to in low doses, not immune suppressing doses in humans. It's considered around 10 milligrams per week. But you definitely don't want to suppress your immune system. But even from from yeast to worms to flies and mice. If you give it late in life, it's still extends lifespan. It's really quite potent. The only downside is that it
Could be toxic. So you have to be extremely careful. And right now it's not available and rapamycin
works by inhibiting. Mtor.
Yeah. Yeah, actually, tore stands for Target of rapamycin. So that's how I am tour was discovered. And when you give animals rapamycin, you're mimicking, low protein intake, which
you remember making this adversity. We've been talking about throughout this entire Series,
right? So your body says, oh my goodness. I'm running out of protein. I need to scavenge protein from within.
And so the body starts recycling old proteins in this process. We talked about earlier called
autophagy and that brings us to another drug spermidine, which is also working on this atop edgy
process. It does. So spermatid is more recent, you've only recently been able to get it on the internet. It has an interesting history. Anthony only one Hawk, the inventor basically of microscopy was looking at his sperm. No one believed him. That those
This, these swimming things down there, but he started to get crystals in the sperm. And that was spermidine. Hence the name
kids, if you want to get into science. Um, and what do we know about sperm Ade now? Because this is a, this is a really old. I mean, there's got an old history but, like really new research that's showing potentially extensions of Life Span. Well, we know it extends lifespan, a yeast and flies and
worms and even mice and mice has a new study. That was really compelling.
If you give sperm it into mice either, when they're young, or even late in life, they live longer and they have better heart function or other youthful capacities. There are two ways that spermidine is known to work in mammalian cells one. Is it stimulates otology just like rapamycin does in the mtor pathway. There's another really interesting property that seems to be true which is it also stabilizes changes to the epigenome which as you know is one of the major causes of Aging.
There have been a number of human studies on permitting.
Particularly revolving around enhancing memory and dealing with memory loss in older
Americans. That's true. We don't know a lot about aging itself. But cognition has greatly improved. A number of studies. The one that stands out for me is the one by Schwartz at El 2018. There were giving people one point, two grams per day, over three months and there was significant enhancement of
memory, only to go back to the history of this stuff. You mentioned earlier. They Anthony Vaughn loan, Hooke discovered, the crystalline structures that led us to Spur.
By examining his own sperm. Presumably his own sperm in a microscope. Is that still? Where we're getting sperm?
A Dean? No, not that I know of.
Where are we getting it for? Are
we getting it from wheat? Germ. It's a lot easier much more abundant. You can also find it in soy
products. That makes me feel better about it.
All right, we've talked about certain activators. We've talked about mtor Inhibitors. But really one of the most exciting classes of drugs is also sort of actually kind of the most boring because it's been around for so very long and ampk activator called metformin which hundreds of millions of people around the world already. Take for
diabetes. Yeah. It was. It's been
Use since the 1950s as the Frontline medicine to bring down glucose levels in type 2 diabetics and it's relatively safe as a drug goes in half the world, it's available over the counter at pharmacies here in the US and in Europe and UK Australia, you need a prescription.
We know that metformin works by activating ampk. Do we know how that process kind of unveils
itself? Well, there are a lot of theories and it's been debated for, over 50 years. One thought, is that the microbiome
Changes. But a leading school of thought that most scientists agree on is that it in activates a protein complex called complex one, which is involved in making energy in mitochondria. And what it does is it lowers the amount of energy that the cell has in the form of ATP. This chemical that we use for energy and then you get my toe hormesis mitochondrial. Hormesis. What doesn't kill. The cell makes it stronger and the reaction is twofold. One is to make more mitochondria. So you get more energy A few days later, but also by inhibiting.
Mtor, it'll improve what's called insulin signaling. So that the blood sugar in that's in your blood. And if your type 2 diabetic, it's too high. It gets sucked out of the bloodstream and utilized which is why it's used to treat type 2
diabetes. And this is another one of those cases where there is perceived diversity and then not just one of these Pathways, but multiple Pathways in this case are
impacted. Yeah. Similarly to all of these factors which are talking to each other. This is a good example. Metformin will lower.
G inhibit mtor, it will activate a PK. Obviously, we talked about, that's what it's mainly doing. But it also raises NAD levels which as we all know will activate the sirtuins. So metformin is a remarkable molecule comes from the plant world. It's very simple. The French hellebore or a lilac plant produces what's called guanines. And these have been known to treat diabetes for many years. In fact, over a century and then chemists have put methyls on them chemically.
I did it so that it's more stable and we call this metformin. And that's what we have to as the drug today.
And we've given this drug to animals and worms its extended lifespans 30 to 40 days, which is no small amount of extension for a
warm. Yeah. I was involved in the mouse study with Rafael De Cobo down at the NIH. And we found that the mice were healthier and longer lived on
Metformin, and what are the other things is? Again, what we want to look for? If we want to know if metformin is working.
At humans, like it works in animals, you know, we're not necessarily just going to look at the life and extension because that takes a long time what are sort of the intermediary things that we're seeing with metformin and humans? You mean in well in animals and that we can look for in humans.
Well, the main one, of course, is glucose lowering but we also see more energy or mitochondria less inflammation and muscle switching. We haven't talked much about muscle type switching butt muscles. As you get older become more. Glycolytic, they start to use more anaerobic.
You can see that Switchback when you give the metformin like they're more like an
athlete and we're seeing all these things in animals and also in
humans, right? And this is where you can, we can speak to a lot of data because millions of people have taken metformin. And one of the most interesting things about it is you can do a retrospective study of tens of thousands of elderly people on Metformin and ask. Okay their type 2 diabetes may be reduced and and slow down, but what about other diseases that they're susceptible to cancer?
Answer heart disease, Alzheimer's Frailty, and the answer. That's quite remarkable. Is that metformin lowers, the risk of all those other diseases.
So, we control for everything else. What we see is that the people who are on Metformin are living
longer than people who don't have type 2 diabetes. It's a remarkable
fact. So now the question becomes okay, take the type to do diabetes part of the equation out. Will we still see an effect? And that is something that's being investigated in this really large.
Study that's underway the team study.
Yeah, you're right. The targeting of Aging by metformin study run by nir. Barzilai down at Albert Einstein College of Medicine. This is a very large study over, many different institutes and hospitals. It's costing tens of millions of dollars. It's taking a while to raise that money. But ultimately the goal is to show to the American FDA that you can Target aging with a drug and slow it down the ultimate goal being having aging the treatable medical
condition. Why is it taking so long to raise money?
For this because this is really, I mean, everybody, I know in the Aging space is excited about this and yet the money is hard to come by
because, well, this is where capitalism has a little bit of a downside, which is that metformin is very cheap. It costs a few cents and it's off patent.
So which means anybody can make it. There's no profit motive for making this drug right
now, right? Sonia is relied on the government and they've given half the money and the rest of the half is relying on donors and he still raising that money.
He's getting started. Fortunately. He's Off to the Races and we should know in the next few years if he's seeing signs of slowing aging and he's looking at a number of things, not just diseases but also things like stability ability to walk strength, these kind of things mental acuity. These are things that would indicate that aging itself as being slow down and he's even now able to measure the human biological clock with accuracy. And that should also be slowed down. If this is truly an anti-aging medicine, we're
seeing
Seeing a lot of doctors get a lot more comfortable with the idea of prescribing that form him off label. Just a few years ago, you know, the constraints of what metformin was actually approved for was keeping it out of the hands of lot of people who thought that it might be good for them in their efforts to slow their aging. There's starting to be a little bit of a shift there.
Well, yeah, I'm seeing a lot more people taking metformin under the approval with the approval of their physician, and part of it is education.
When typically when a doctor sees the evidence and there's extensive literature and sometimes the patient takes the information to the doctor or our book, the doctor in most cases is convinced that this is worth the risk. Now. It's not risk-free. We should mention that, metformin has some. Downsides one? Is that it can cause lactic acidosis? Which is quite a severe condition. It can be fatal to have to be very careful there. But most people are find on Metformin. The biggest thing that happens to them is
Is that they have an upset, stomach, lack of hunger, which can actually be a good thing if you want to lose weight as well.
But doctors now are saying, okay, they're advising their patients out to these potential side effects and also saying, yeah, either because that doctor is sold on. The idea that there's a potential aging benefits here anti-aging benefit here or one of the other things you and I have talked about before is doctors are in.
Reaching Lee getting sick of waiting until patients or full-blown sick to prescribe the medications and they're prescribing it to pre-diabetic people and pre. What we might call pre pre diabetic
people. Well, there's a shift in in medicine and the way doctors are looking at their patients more and more doctors are saying, okay. Let's not wait till the patient, is so sick that we have to treat them. Let's get ahead of that and let's start treating them
earlier. The one other thing that people should talk to the doctors about if they're considering trying to get on that.
Foreman is the concerns about the connection between metformin and muscle loss,
right? Particularly in the elderly. This is an issue. But actually if you look at the data and then in a couple of human studies metformin doesn't make a big difference to muscle size. It probably makes a difference if you're trying to win mr. Universe, but other than that the difference is really slide. You look at the graphs. It's only 5% difference and actually 5% difference. I'll give up 5% body size for a longevity, any day.
But the other important thing is that those muscles on Metformin would just as strong as the others and had less inflammation. So there's other benefits to that what some people are doing, just in an abundance of caution is taking metformin on days that they don't exercise. And if you're wondering, why does it affect exercise? We'll really it's pretty obvious. It reduces the body's ability to make energy and so you don't feel a strong on the days that you take Metformin. So you do less reps, fewer reps. And so what you could really do is just put a little bit of extra effort in and probably make up that five percent
difference.
If people are interested in the effects of metformin, but are not able to work with a doctor to get a prescription for it. Or if they've tried out metformin and it just doesn't sit well with them, which is the case with that. 20% of people. There's another alternative that works on some of the same Pathways activating ampk. That's
berberine. That's right. This is a molecule from the Plant World bark and Roots. You can find. It's a yellow substance. Again, it's Philly insoluble. So if you want to take it, take it.
Some food yogurt, olive oil is kind of stuff. I'm but it's been remarkable. What's been found in animals? And even in people that it can mimic the effects of metformin specifically. What it does is again, it binds to this complex one and reduces chemical energy in the body. And in reaction. This motor hormesis is to amplify of mitochondria and make the body more sensitive to insulin and lower. The blood glucose. We've seen this in my lab in mice, and human Studies have actually validated this as well. The doses are high.
One to two grams per day, but it does seem to
work. And when you see it does seem to work. You mean not just showing, you know, the activation of ampk and increased mitochondrial energy, but we actually in mice, have seen increases pretty substantial increases in life span.
Yeah, actually, it's really interesting in mice, buh-burn. Will extend the lifespan of mice treated with chemotherapy and have a pretty big lifespan extension of normally aged mice. That's also true in fruit flies. So it seems to be a common mechanism.
That you lower the energy in an animal and it responds by living longer.
And I think you said you got to take quite a bit of this stuff
though. Yeah, the clinical studies. It's at least a gram. There's one that worked with two grams, but it does seem to work just like metformin in improving. The body's sensitivity to insulin and lowering the blood glucose levels, which is a good sign that it's going to have future health benefits.
And you concerns about side effects with bourbon.
I'm unaware of any downside of bourbon,
which is a berber and does have some of the similar side effects of metformin. We don't know.
No, I different groups of people might be different. But you're looking at diarrhea, constipation gas potentially upset
stomach, right, you know, molecules perfect. But this one's really interesting because it's a natural and commonly available one that you can try at home. Of course, talk to your doctor first. Oh,
yeah. All right. Well, that kind of brings us to try at home. And again, with the caveat that we're not telling anybody what to do. We're not giving them medical advice. You're not a doctor. I know you have been
The open about what you do. That has changed over the years, but let's just sort of take it through the things that you started doing, you know, 20 years ago, 10 years ago, five years ago, just start from the sort of a chronology. When you started investigating Resveratrol. You also started taking Resveratrol. How did you know how much to take though? Because you were giving Resveratrol to yeast and eventually, to,
Mice. Well, it's not a one-to-one. It's not like you should take 3,000 times as much as the mouse had. This
is were three thousand times bigger than a
mouse. Right? Right. It's not, it's not just proportional. It's actually more related to our surface are and how much the drug can get into our bodies versus The Mouse, and the calculation for a mouse, which is called the allometric scaling is about 12. So you multiply, let's say, if the mouse has 100 mg 1, .2 G for human, for a rat, it's three for a mini pig. It's one to one turns out we have about the same surface areas as a
And so you take about a gram of Resveratrol every day
I do. And I've been taking that since about 2004 and I but I but like I said, it's you can't just put it in water and drink it, add some fat to it. Yeah. So I typically have some yogurt, a couple of spoonfuls, not a lot, because I'm trying to fast until dinner, but I could mix it with olive oil. Olive oil recently, as we mentioned earlier, in a previous episode seem to be really good for activating sirtuins. But also, you can dissolve Resveratrol in it. You get a 2 /, you do.
Don't have a lot of it as a lot of calories in olive oil. I don't want to break the fast severely but, you know, mix it with bit of vinegar and basil leaves and it doesn't taste too
bad. Okay, so Resveratrol, you taking about a gram a day in the morning. Also, in the morning, you take n MN
I do, and there you don't have to worry about food. It's dissolved easily. You can put it in water or swallow, it put it under your tongue. And so I do that. That's my main combo in the morning.
How much Anna men are
you taking? And again, it's G, but that's not a guess that's actually based on the human.
Studies that we've done that. Show that a gram over 10 days. Raises your NAD levels about to
fold and that's sort of the dosing amount that we're seeing in a lot of a human studies. Now, that is both the past studies and the current study,
the roiling, I take 1 gram of nmn every every morning along with my Resveratrol. The reason is in humans, we know that that doubles NAD levels, which is important because someone my age has half the levels of NAD. Then I did when I was 20, but you can go as high as two grams and triple the amount.
It's important to mention that I take these at a certain time of day based on science as well. I take these in the morning because that's when the natural rise in NAD and sort one activity should happen and we actually know this that the sort. So one NAD, cycle is part of our body's natural 24 hour clock. So it one regulates a protein called b-mail that controls. The genes that tell us whether it's night or day. Should we be hungry or not? Whether we should have where we have jet lag or not. And I do find anecdotally. That nmn is remarkably. Good at preventing jet lag.
Well, I can reset my body's clock ostensibly through this sort one b-mail
pathway. You're also taking metformin. Yes, how much
when I take 800 milligrams at night.
Okay, and you take that at night
because well, because doctors, tell me that. It's a good time to simulate a fast. I take it with my dinner just after. And then, through the night, I'm presumably having low levels of glucose in my body has all the benefits of stimulating those repair Pathways those survival Gene.
Ins. And that's the most recent thing that you've added to your
regimen. It is actually what happened was. I had terrible Blood by chemistry. I was eating badly, I gained weight. I wasn't sleeping. I was stressed and those numbers just went through the roof and I said I've got to do something. So I went on nmn and things were somewhat rectified and then I added metformin and they really got back to my
optimal. We mentioned earlier, some concerns about exercise, metformin your practices, where that's
concerned.
Yeah, I pulse metformin. It doesn't sit well in my stomach anyway, so on days. Where I know next day, I'm going to exercise and lift weights. I might skip metformin that night
before and then there's also
spermatid there is you can buy it now. It's there's a company that makes it in pure from very low levels of gluten. And just the last few months. I've added that to my protocol and we'll have to see how my numbers look on inside tracker.
Okay, so that's not that's not something you've adopted in your like I'm definitely taking with it. This is I'm adopted and I'm
Testing it out to see how it
works. I am, and I actually, I advise that companies, the first supplement company. I am advising and I did that because I wanted to look at the human clinical trials and they look really promising as well.
How much of that are you
taking a gram as well? Okay,
you are also periodically taking five certain Kirsten aimed at sentence
itself. There are clinical trials, being run out of the Mayo Clinic for fizzy didn't and for Corsten. These are high doses, the typical.
G taken one day a week for a matter of months. I'm myself. I'm on a maintenance dose. I take about half a gram of each every day.
Let's take this morning through Nature's really quickly Resveratrol 1 gram
in the morning with yogurt or olive oil
and a man as well. A gram. Yep, face it in a cure certain
half a gram in the yogurt Sperma Dean definitely sperm edenia in the morning about a gram
and then in the evenings if you're not working out the next day metformin how much
Mg. Okay, that's it. That's it.
Now, you're not most people, a lot of other people are going to be different, you don't advise people, but it might be a good place for people to start their conversation with their doctor though.
Yeah, I think so. Most doctors are open to looking at, stay inside track of data and hearing about the latest science. It's very difficult for them to keep up with it. One of the reasons we're doing this podcast in the first
place. So, David, this has been a really comprehensive conversation, even
Till we could have gone deeper on any one of these drugs or supplements. Maybe we'll do that in future episodes in a future season of Life Span podcast. But what we're trying to do today is really give people an opportunity to really start thinking about whether this might be something that they want to bring into their lives. And if so how of course again in consultation with their
physician and monitoring this is important.
You don't know if you're doing good or harm to your body unless you measure it, particularly your liver. You can measure what's called a St. Alt I do that routinely just to make sure nothing's going wrong in that
regard. Our next episode is
things that are not supplements things. Maybe you could regard them as being on more of The Cutting Edge. Things like testosterone growth hormone exosomes, peptides. We're going to dive deep into those as well. All right, sounds like fun. Yeah. Let's do it. If you're enjoying this podcast and would like to support us, please subscribe.
I'm on YouTube. Apple podcasts and Spotify on Apple. You have the opportunity to leave us up to a five star review. Also, check out the sponsors that we mentioned at the start of the episode. That's probably the best way to support the show. We also have a patreon account. That's patreon.com slash David Sinclair and there you can support the show at any level. You'd like. Thanks again for joining us on this episode of the lifespan podcast.
