Dr. David Sinclair: The Biology of Slowing & Reversing Aging

00:00:00.280 | - Welcome to the Huberman Lab Podcast,

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.600 | and I'm a professor of neurobiology and ophthalmology

00:00:13.040 | at Stanford School of Medicine.

00:00:14.960 | Today, my guest is Dr. David Sinclair,

00:00:17.320 | professor of genetics at Harvard Medical School

00:00:19.960 | and co-director of the Paul F. Glenn Center

00:00:22.700 | for the Biology of Aging.

00:00:24.640 | Dr. Sinclair's work is focused on why we age

00:00:27.800 | and how to slow or reverse the effects of aging

00:00:30.520 | by focusing on the cellular and molecular pathways

00:00:33.740 | that exist in all cells of the body

00:00:36.080 | and that progress those cells over time

00:00:38.200 | from young cells to old cells.

00:00:40.920 | By elucidating the biology of cellular maturation and aging,

00:00:45.300 | Dr. Sinclair's group has figured out intervention points

00:00:48.060 | by which any of us, indeed all of us,

00:00:50.760 | can slow or reverse the effects of aging.

00:00:53.240 | What is unique about his work is that it focuses

00:00:55.480 | on behavioral interventions, nutritional interventions,

00:00:58.760 | as well as supplementation

00:01:00.680 | and prescription drug interventions

00:01:02.920 | that can help us all age more slowly

00:01:05.580 | and reverse the effects of aging in all tissues of the body.

00:01:09.240 | Dr. Sinclair holds a unique and revolutionary view

00:01:11.860 | of the aging process,

00:01:13.340 | which is that aging is not the normal

00:01:15.560 | and natural consequence that we all will suffer,

00:01:18.580 | but rather that aging is a disease

00:01:20.780 | that can be slowed or halted.

00:01:22.800 | Dr. Sinclair continually publishes original research articles

00:01:26.420 | in the most prestigious

00:01:27.680 | and competitive scientific journals.

00:01:29.920 | In addition to that, he's published a popular book

00:01:32.740 | that was a New York Times bestseller.

00:01:34.620 | The title of that book is "Lifespan,

00:01:36.320 | Why We Age and Why We Don't Have To."

00:01:38.720 | He is also very active in public-facing efforts

00:01:41.440 | to educate people on the biology of aging

00:01:43.600 | and slowing the aging process.

00:01:45.740 | Dr. Sinclair and I share a mutual interest and excitement

00:01:48.800 | in public education about science.

00:01:51.400 | And so I'm thrilled to share with you

00:01:53.460 | that we've partnered and Dr. David Sinclair

00:01:55.800 | is going to be launching the "Lifespan" podcast,

00:01:58.020 | which is all about the biology of aging

00:01:59.840 | and tools to intervene in the aging process.

00:02:02.520 | That podcast will launch Wednesday, January 5th.

00:02:06.040 | You can find it at the link in the show notes

00:02:08.580 | to this episode today.

00:02:10.080 | As well, you can subscribe to that podcast

00:02:12.680 | on YouTube, Apple, or Spotify,

00:02:14.680 | or anywhere that you get your podcasts.

00:02:16.280 | Again, the "Lifespan" podcast featuring Dr. David Sinclair

00:02:19.600 | begins Wednesday, January 5th, 2022.

00:02:22.640 | Be sure to check it out.

00:02:23.580 | You're going to learn a tremendous amount of information

00:02:26.080 | and you're going to learn both

00:02:27.720 | the mechanistic science behind aging,

00:02:29.920 | the mechanistic science behind reversing the aging process,

00:02:32.960 | and practical tools that you can apply

00:02:35.200 | in your everyday life.

00:02:36.760 | In today's episode, Dr. Sinclair and I talk about

00:02:39.640 | the biology of aging and tools to intervene in that process.

00:02:42.480 | And so you might view today's episode

00:02:44.520 | as a primer for the "Lifespan" podcast

00:02:47.500 | because we delve deep into the behavioral tools,

00:02:50.040 | nutritional aspects, supplementation aspects

00:02:53.080 | of the biology of aging.

00:02:54.480 | We also talk about David's important discoveries

00:02:56.900 | of the sirtuins, particular molecular components

00:02:59.960 | that influence what is called the epigenome.

00:03:02.200 | And if you don't know what the epigenome is,

00:03:03.920 | you will soon learn in today's episode.

00:03:05.880 | Coming away from today's episode,

00:03:07.320 | you will have in-depth knowledge about the biology of aging

00:03:10.240 | at the cellular, molecular,

00:03:12.020 | and what we call the circuit level,

00:03:13.320 | meaning how the different organs and tissues of the bodies

00:03:15.800 | age independently and how they influence

00:03:17.760 | the aging of each other.

00:03:19.540 | Today's episode gets into discussion

00:03:21.500 | about many aspects of aging and tools to combat aging

00:03:25.000 | that have not been discussed on any other podcasts

00:03:27.740 | or in the book "Lifespan."

00:03:29.780 | Before we begin, I'd like to emphasize that this podcast

00:03:32.620 | is separate from my teaching and research roles at Stanford.

00:03:35.400 | It is, however, part of my desire and effort

00:03:37.420 | to bring zero cost to consumer information about science

00:03:39.900 | and science-related tools to the general public.

00:03:42.460 | In keeping with that theme,

00:03:43.480 | I'd like to thank the sponsors of today's podcast.

00:03:46.240 | Our first sponsor is Roca.

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00:03:52.540 | I've spent a lifetime working on the visual system.

00:03:55.000 | I can tell you that the visual system has to contend

00:03:56.820 | with a number of different challenges,

00:03:58.580 | such as when you move from a bright area outside

00:04:01.260 | to an area where there are shadows,

00:04:03.140 | you have to adjust a number of things in your visual system

00:04:05.340 | so that you can still see things clearly.

00:04:07.200 | One problem with a lot of eyeglasses and sunglasses

00:04:09.860 | is they don't take that biological feature into account

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00:07:42.200 | And now my conversation with Dr. David Sinclair.

00:07:45.520 | Thank you for coming.

00:07:46.360 | - Thanks for having me here.

00:07:47.440 | It's good to see you.

00:07:48.600 | - This is mate, by the way, that we're toasting at 11 AM.

00:07:52.440 | Unlike other podcasts, well, I don't drink alcohol,

00:07:56.760 | so I'm boring that way.

00:07:58.980 | But truly, thanks for being here.

00:08:02.080 | I have a ton of questions for you.

00:08:03.840 | We go way back in some sense,

00:08:06.600 | but that doesn't mean that I don't have many, many questions

00:08:10.640 | about aging longevity, lifespan, actionable protocols

00:08:15.640 | to increase how long we live, et cetera.

00:08:18.600 | And I just want to start off with a very simple question

00:08:21.960 | that I'm not even sure there's an answer to,

00:08:24.080 | but what is the difference between longevity,

00:08:27.880 | anti-aging and aging as a disease?

00:08:30.460 | Because I associate you with a statement,

00:08:33.500 | aging is a disease.

00:08:35.580 | - Right, well, so longevity is the more academic way

00:08:39.540 | we describe what we research.

00:08:41.340 | Anti-aging is kind of the same thing,

00:08:43.620 | but it's got a bad rap because it's been used

00:08:45.660 | by a whole bunch of people

00:08:46.500 | that don't know what they're talking about.

00:08:48.300 | So I really don't like that term anti-aging,

00:08:50.680 | but aging as a disease and longevity

00:08:52.540 | are perfectly valid ways to talk about this subject.

00:08:56.620 | So let's talk about aging as a disease.

00:08:58.880 | When I started my research,

00:09:00.800 | disease here at Harvard Medical School,

00:09:03.980 | it was considered if there's something

00:09:06.100 | that's wrong with you and it's a rare thing,

00:09:10.120 | has to be less than 50% of the population,

00:09:12.760 | that's definitely a disease.

00:09:14.200 | And then people work their whole lives

00:09:16.020 | to try and cure that condition.

00:09:18.340 | And so I looked up what's the definition of aging

00:09:20.200 | and it says, well, it's a deterioration in health

00:09:22.600 | and sickness and you can die from it, typically you do.

00:09:25.360 | Something that sounds pretty much like a disease,

00:09:28.720 | but the caveat is that if more than half the population

00:09:32.320 | gets this condition, aging,

00:09:34.860 | it's put in a different bucket,

00:09:36.420 | which is first of all, that's outrageous

00:09:37.980 | 'cause it's just a totally arbitrary cutoff.

00:09:40.780 | But think about this,

00:09:41.620 | that we're ignoring the major cause of all these diseases.

00:09:45.400 | Aging is 80 to 90% the cause of heart disease, Alzheimer's.

00:09:49.180 | If we didn't get old and our bodies stayed youthful,

00:09:52.060 | we would not get those diseases.

00:09:53.380 | And actually what we're showing in my labels,

00:09:54.980 | if you turn the clock back in tissues, those diseases go away.

00:09:59.140 | So aging is the problem.

00:10:00.620 | And instead through most of the last 200 years,

00:10:04.120 | we've been sticking band-aids on diseases

00:10:06.120 | that have already occurred because of aging,

00:10:08.560 | and then it's too late.

00:10:10.300 | So there are a couple of things.

00:10:11.180 | One is we want to slow aging down

00:10:12.520 | so we don't get those diseases.

00:10:14.260 | And when they do occur, don't just stick a band-aid on,

00:10:16.860 | reverse the age of the body

00:10:18.020 | and then the diseases will go away.

00:10:20.320 | - That clarifies a lot for me, thank you.

00:10:23.380 | Can we point to one specific general phenomenon in the body

00:10:28.220 | that underlies aging?

00:10:30.020 | - Yeah, well, that's contentious

00:10:31.860 | because scientists like to come up with new hypotheses.

00:10:34.740 | It's how they build their careers.

00:10:37.220 | But fortunately, during the 2000s,

00:10:39.820 | we settled on eight or nine major causes of aging.

00:10:43.460 | We called them hallmarks

00:10:44.460 | 'cause causes was a little bit too strong.

00:10:47.200 | But these eight or nine causes,

00:10:49.420 | at least for the first time,

00:10:50.420 | allowed us to come around and talk together.

00:10:53.460 | And we put them on a pizza

00:10:55.700 | so everyone got an equal weighting, equal slices.

00:10:59.060 | And before that, by the way,

00:11:00.500 | we were trying to kill each other in the field.

00:11:02.620 | It was horrible.

00:11:03.740 | - Interesting that you guys work on aging

00:11:05.340 | and you're trying to kill each other.

00:11:06.180 | - Yeah, isn't it?

00:11:07.020 | Well, kill each other's careers.

00:11:08.880 | I mean, I like to think I was fairly generous,

00:11:10.620 | but I was one of the kids

00:11:11.940 | and the old guard really didn't like the new guard.

00:11:14.040 | We just came along in the 1990s and '90s

00:11:16.540 | and said free radicals don't do much.

00:11:19.240 | There were actually genes called longevity genes,

00:11:21.520 | and that caused a whole ruckus.

00:11:22.800 | And there was this competition for what never happened,

00:11:27.680 | which was a Nobel Prize for this.

00:11:29.680 | And it just led to a lot of competition.

00:11:31.480 | I would go to meetings

00:11:32.600 | and people would shout at each other and just backstab.

00:11:35.960 | It was horrible.

00:11:37.400 | But then fortunately in the 2000s,

00:11:38.600 | we rallied around this new map of aging

00:11:41.820 | with these causes or hallmarks.

00:11:44.480 | But I think that there's one slice of the pizza

00:11:46.820 | that is way larger than the others.

00:11:48.860 | And we can get to that,

00:11:49.860 | but that's the information in the cell

00:11:52.120 | that we call the epigenome.

00:11:54.520 | - Well, tell us a little bit more about the epigenome.

00:11:57.240 | Frame it for us, if you will,

00:11:59.520 | and then we'll get into ways

00:12:01.600 | that one can adjust the epigenome in positive ways.

00:12:05.480 | - Yeah, so in science, what I like to do,

00:12:07.680 | I'm a reductionist, is to boil it down.

00:12:10.120 | And I actually ended up boiling aging down to an equation,

00:12:14.100 | which is the loss of information due to entropy.

00:12:17.760 | It's a hard thing to overcome

00:12:18.860 | the second law of thermodynamics, that's fair.

00:12:21.380 | But this equation really represents the fact

00:12:24.320 | that I think aging is a loss of information

00:12:27.440 | in the same way that when you Xerox something,

00:12:31.620 | a thousand times you'll lose that information

00:12:33.500 | or you try to copy a cassette tape,

00:12:35.360 | or even if you send information across the internet,

00:12:37.300 | some of it will get lost.

00:12:39.340 | That's what I think is aging.

00:12:41.040 | And there are two types of information in the body.

00:12:43.440 | There is the genetic information, which is digital,

00:12:46.420 | ATCG, the chemical letters of DNA,

00:12:49.200 | but there's this other part of the information in the body

00:12:51.680 | that's just as important, it's essential in fact,

00:12:54.800 | and that's the systems that control

00:12:57.780 | which genes are switched on and off,

00:12:59.680 | in what cell, at what time,

00:13:01.480 | in response to what we eat, et cetera.

00:13:03.820 | And it turns out that 80% of our future longevity and health

00:13:07.320 | is controlled by this second part,

00:13:08.840 | the epigenetic information, the control systems.

00:13:11.820 | I liken the DNA to the music that's on a DVD

00:13:15.700 | or a compact disc, for the younger people,

00:13:17.160 | we used to use these things.

00:13:18.200 | - I recall. - Yeah.

00:13:19.700 | And then the epigenome is the reader that says,

00:13:21.480 | "Okay, in this cell, we need to play that set of songs.

00:13:25.660 | And in this other cell,

00:13:26.500 | we have to play a different set of songs."

00:13:28.280 | But over time, aging is the equivalent of scratching the CD

00:13:31.660 | and the DVD so that you're not playing the right songs

00:13:34.480 | and cells, when they don't hear the right songs,

00:13:37.600 | they get messed up and they don't function well.

00:13:40.160 | And that is what I'm saying is the main driver of aging.

00:13:43.320 | And these other hallmarks are largely manifestations

00:13:46.260 | of that process.

00:13:47.540 | - Can we go a little deeper into what these scratches are?

00:13:52.140 | Is it the way that the DNA are packed into a cell?

00:13:57.020 | Is it the way that they're spaced?

00:14:00.860 | What are the scratches that you're referring to?

00:14:04.700 | - So DNA is six foot long.

00:14:06.200 | So if you join your chromosomes together,

00:14:07.820 | you get about six foot per cell.

00:14:09.880 | So there's enough to go to the moon and back eight times

00:14:11.840 | in your body and it has to be wrapped up to exist inside us.

00:14:16.140 | But it's not just wrapped up willy-nilly.

00:14:18.260 | It's not just a bundle of string.

00:14:20.340 | It's wrapped up very carefully in ways that dictates

00:14:23.200 | which genes are switched on and off.

00:14:25.360 | And when we're developing in the embryo,

00:14:27.720 | the cell marks the DNA with chemicals that says,

00:14:30.720 | "Okay, this gene is for a nerve cell.

00:14:32.780 | You, you cell, will stay a nerve cell

00:14:35.380 | for the next hundred years, if you're lucky.

00:14:37.620 | Don't turn into a skin cell, that would be bad."

00:14:40.760 | And those chemicals, there are many different types

00:14:43.480 | of chemicals, but one's called methylation.

00:14:45.520 | Those little methyls will mark which songs get played

00:14:48.880 | for the rest of your life.

00:14:50.360 | And there are other marks that change daily.

00:14:52.760 | But in total, what we're saying is that the body

00:14:55.280 | controls the genome through the ability to mark the DNA

00:14:59.760 | and then compact some parts of it, silence those genes,

00:15:04.480 | don't read those genes, and open others, keep others open,

00:15:08.400 | that should stay open.

00:15:09.800 | And that pattern of genes that are silent and open,

00:15:13.620 | silent, open, is what dictates the cell's type,

00:15:17.000 | the cell's function.

00:15:18.320 | And then the scratches are the disruption of that.

00:15:21.160 | So genes that were once silent,

00:15:24.160 | and you could say it's a gene that is involved in skin,

00:15:28.520 | it's starting to come on in the brain,

00:15:29.960 | shouldn't be there, but we see this happen,

00:15:32.060 | and vice versa, the gene might get shut off over time

00:15:34.420 | during aging, cells over time lose these structures,

00:15:38.440 | lose their identity, they forget what they're supposed to do,

00:15:41.700 | and we get diseases.

00:15:43.280 | We call that aging, and we can measure that.

00:15:46.100 | In fact, we can measure it in such a way that we can predict

00:15:48.560 | when somebody is going to die,

00:15:49.980 | based on the changes in those chemicals.

00:15:53.400 | - Are these changes the same sorts of changes

00:15:55.720 | that underlie the outward body surface manifestations

00:16:00.600 | of aging that most of us are familiar with?

00:16:02.320 | Graying of the hair, wrinkling of the skin,

00:16:04.400 | drooping of the face,

00:16:07.780 | walking around New York lately, it's amazing to me.

00:16:11.940 | There are certain people that seem to walk

00:16:14.100 | looking down at the sidewalk

00:16:15.500 | because their spine is essentially in a C shape, right?

00:16:19.740 | A hallmark, if you will,

00:16:21.260 | of aging that most of us are familiar with.

00:16:23.760 | Are these same sorts of DNA scratches associated with that?

00:16:26.860 | Or are we talking about people that potentially

00:16:29.080 | are going to look older, but simply live longer?

00:16:32.160 | - Well, it's actually, you are as old as you look,

00:16:34.940 | if you want to generalize.

00:16:36.720 | So let's start with centenarian families.

00:16:39.260 | These are families that tend to live over 100.

00:16:42.020 | When they're 70, they still look 50 or less.

00:16:45.020 | So it is a good indicator.

00:16:47.540 | It's not perfect because you can,

00:16:48.980 | like me, grow up in Australia

00:16:50.740 | and accelerate the aging of your skin,

00:16:54.020 | but in general, how you look.

00:16:55.540 | No one's ever dyed from gray hair,

00:16:57.460 | but overall you can get a sense

00:16:59.360 | just from the ability of skin to hold itself up,

00:17:02.540 | how thin it is, the number of wrinkles.

00:17:04.640 | That is actually, a great paper just came out

00:17:07.440 | that said that an AI system looking at the face

00:17:10.060 | could very accurately predict someone's age.

00:17:12.220 | - Very interesting.

00:17:13.700 | So I started off in developmental neurobiology.

00:17:16.900 | So one of the things that I learned early on

00:17:19.500 | that I still believe wholeheartedly

00:17:22.620 | is that development doesn't stop at age 12 or 15

00:17:27.620 | or even 25, that your entire life

00:17:30.700 | is one long developmental arc.

00:17:34.300 | So in thinking about different portions

00:17:37.220 | of that developmental arc,

00:17:38.760 | the early portion of infancy and especially puberty

00:17:43.260 | seem like especially rapid stages of aging.

00:17:47.060 | And I know we normally look at babies and children

00:17:49.740 | and kids in puberty and we think,

00:17:50.880 | oh, they're so vital, they're so young.

00:17:53.860 | And yet the way you describe these changes in the epigenome

00:17:58.140 | and the way you have framed aging as a disease

00:18:01.080 | leads me to ask, are periods of immense vitality

00:18:06.080 | the same periods when we're aging faster?

00:18:11.340 | - Yes, yes, and this is something I've never talked about,

00:18:15.060 | at least not publicly, so this is a really good question.

00:18:18.100 | So those chemicals we can measure,

00:18:20.300 | it's also known as the Horvath clock,

00:18:21.700 | it's the biological clock,

00:18:22.900 | it's separate from your chronological age.

00:18:25.300 | So actually what I didn't mention is that

00:18:27.140 | when the AI looked at the faces of those people,

00:18:29.580 | they could predict their biological age, their internal age.

00:18:33.480 | So your skin represents the age of your organs as well.

00:18:36.820 | And the people that look after themselves,

00:18:38.560 | we can talk about how to do that later,

00:18:40.500 | but there are some people that are 10, 20 years younger

00:18:42.880 | than other people biologically.

00:18:46.100 | And it turns out if you measure that clock from birth

00:18:48.480 | or even before birth, if you look at animals,

00:18:50.880 | there's a massive increase in age

00:18:53.380 | based on that clock early in life.

00:18:55.960 | So you're right, so that's a really important point

00:18:58.480 | that you have accelerated aging

00:19:00.460 | during the first few years of life,

00:19:02.100 | and then it goes linear towards the rest of your life.

00:19:05.520 | But there's another interesting thing you brought up,

00:19:07.000 | which is that we're finding that the genes

00:19:08.740 | that get messed up, that get scratched,

00:19:11.040 | that are leading to aging

00:19:13.060 | are those early developmental genes.

00:19:15.520 | They come on late in life and just mess up the system,

00:19:19.000 | and they seem to be particularly susceptible

00:19:20.840 | to those scratches.

00:19:22.480 | So what's causing the scratches?

00:19:24.240 | Well, we know of a couple of things in my lab,

00:19:25.920 | we figured out one is broken chromosomes, DNA damage,

00:19:30.160 | particularly cuts to the DNA breaks.

00:19:32.300 | So if you have an X-ray or a cosmic ray,

00:19:35.360 | or even if you go out in the sun

00:19:36.720 | and you'll get your broken chromosomes,

00:19:38.840 | that accelerates the unwinding

00:19:41.480 | of those beautiful DNA loops that I mentioned.

00:19:44.380 | We can actually do this to a mouse.

00:19:47.860 | We can accelerate that process,

00:19:50.160 | and we get an old mouse, 50% older,

00:19:52.520 | and it has this bent spine kyphosis.

00:19:54.680 | It has gray hair, its organs are old.

00:19:56.840 | So we now can control aging in the forwards direction.

00:19:59.960 | The other thing that accelerates aging

00:20:01.540 | is massive cell damage or stress.

00:20:05.160 | So we pinched nerves,

00:20:07.280 | and we saw that their aging process

00:20:09.100 | was accelerated as well.

00:20:10.600 | - Incredible.

00:20:11.440 | Yeah, this is more of an anecdotal phenomenon.

00:20:15.080 | It is an anecdotal phenomenon,

00:20:16.760 | but this experience of in junior high school,

00:20:20.240 | you know, going home for a summer

00:20:21.720 | and you come back, high school in the US,

00:20:24.560 | usually starts eighth or ninth grade

00:20:26.080 | or grade eight or grade nine for your Canadians.

00:20:28.480 | And then some of the kids,

00:20:32.580 | like they grew beards over the summer,

00:20:34.600 | or they completely matured quickly over the summer.

00:20:37.800 | Do you think there's any reason to believe

00:20:39.540 | that rates of entry into and through puberty

00:20:42.900 | can predict overall rates of aging?

00:20:47.280 | In other words, if a kid is a slow burner, right?

00:20:52.800 | They basically acquire the traits of puberty

00:20:57.040 | slowly over many years.

00:20:59.020 | Can we make some course prediction

00:21:01.800 | that they are going to live a long time

00:21:03.740 | versus a kid that goes home for the summer

00:21:05.740 | and comes back a completely different organism

00:21:08.380 | or appearing to be a completely different organism?

00:21:10.800 | Like they basically age very quickly in the summer.

00:21:12.700 | Does that mean they're aging very quickly overall?

00:21:14.900 | - Well, yeah, I don't want to scare anybody.

00:21:16.760 | - Sure.

00:21:17.820 | - That there are studies that show

00:21:20.840 | that the slower you take to develop,

00:21:23.440 | it also is predictive of having a longer, healthier life.

00:21:26.400 | And it may have something to do with growth hormone.

00:21:30.100 | We know that growth hormone is pro-aging.

00:21:32.660 | Anyone who's taking growth hormone, pay attention.

00:21:37.280 | We know that- - Just look at someone

00:21:38.240 | who's taking growth hormone.

00:21:39.840 | They often will acquire these characteristics of vitality,

00:21:42.960 | like improved smoothness of skin,

00:21:44.760 | but their whole body shape changes often.

00:21:47.080 | - Yeah, I mean, you'll feel better

00:21:49.160 | for a short amount of time.

00:21:50.240 | You'll build up muscle.

00:21:51.080 | You feel great.

00:21:52.120 | But it's like burning your candle at both ends.

00:21:54.680 | Ultimately, if you want to live longer,

00:21:56.640 | you want less of that.

00:21:57.720 | And the animals that have been generated

00:22:00.600 | and mutants that have low growth hormone,

00:22:03.160 | sometimes these are dwarfs.

00:22:04.600 | They live the longest by far.

00:22:07.660 | A guy in my lab, Michael Bongkowski,

00:22:10.040 | he had the longest-lived mouse.

00:22:11.840 | A mouse typically lives about two and a bit years.

00:22:14.360 | He had a mouse that lived five years,

00:22:16.420 | and he gave it caloric restrictions for fasting

00:22:18.980 | combined with one of these dwarf mutations,

00:22:20.820 | low growth hormone.

00:22:22.180 | I think he called it Yoda.

00:22:23.920 | But you look at who lives the longest.

00:22:27.580 | It's the really small people.

00:22:29.500 | This is a bit anecdotal,

00:22:31.460 | but it sounds like it might be true,

00:22:34.380 | is that the people who played the Munchkins

00:22:36.140 | in "The Wizard of Oz,"

00:22:37.280 | many of them went on to live into their 90s and beyond.

00:22:39.920 | - Really? - Yeah.

00:22:41.760 | - Amazing.

00:22:42.600 | - Oh, there are some Laurent dwarfs as well.

00:22:44.980 | There are dwarf mutations in South America,

00:22:49.160 | and they seem to be protected

00:22:50.380 | against many of the diseases of aging.

00:22:52.200 | You barely ever see heart disease or cancer

00:22:54.080 | in these families.

00:22:55.360 | - So I, having owned a very large dog breed,

00:22:58.580 | a Bulldog Mastiff,

00:22:59.600 | who lived a long life for a bulldog, 11 years,

00:23:03.120 | but there are many dogs that will live 12, 16 years

00:23:07.520 | that are smaller dogs.

00:23:08.880 | Can we say that there's a direct relationship

00:23:10.840 | between body size and longevity,

00:23:13.160 | or duration of life?

00:23:16.220 | - Well, there is,

00:23:17.560 | but that doesn't mean that you're a slave

00:23:19.220 | to your early epigenome,

00:23:21.620 | nor to your genome.

00:23:23.220 | The good news is that the epigenome can change.

00:23:26.220 | Those loops and structures can be modified

00:23:29.140 | by how you live your life.

00:23:30.840 | And so if you're born tall, and I wasn't,

00:23:33.560 | and I wished at the time I did grow,

00:23:36.480 | but no matter what size you are,

00:23:38.840 | you can have a bigger impact on your life

00:23:40.980 | than anything your genes give you.

00:23:42.900 | 80% is epigenetic, not genetic.

00:23:45.920 | - So let's talk about some of the things that people can do.

00:23:48.220 | And I've kind of batched these into categories

00:23:51.400 | rather than just diving right into actionable protocols.

00:23:56.400 | So the first one relates to food, blood sugar, insulin.

00:24:01.580 | This is something I hear a lot about,

00:24:04.580 | that fasting is good for us,

00:24:06.340 | but rarely do I hear why it's good for us.

00:24:11.000 | One of the reasons I'm excited to talk to you today

00:24:12.880 | is because I want to drill into the details of this,

00:24:15.640 | because I think understanding the mechanism

00:24:17.580 | will allow people to make better choices

00:24:19.860 | and not simply to just decide

00:24:22.240 | whether or not they're going to fast or not fast,

00:24:24.060 | or how long they're going to fast,

00:24:25.600 | I think should be dictated

00:24:26.500 | by some understanding of the mechanism.

00:24:28.480 | So why is it that having elevated blood sugar,

00:24:32.920 | glucose, and insulin ages us more quickly,

00:24:36.600 | and/or why is it that having periods of time each day

00:24:40.800 | or perhaps longer can extend our lifespan?

00:24:45.180 | - Well, let's start with what I think was a big mistake,

00:24:48.340 | was the idea that people should never be hungry.

00:24:52.140 | We live in a world now

00:24:53.100 | where there's at least three meals a day,

00:24:55.440 | and then we've got companies selling bars

00:24:57.780 | and snacks in between.

00:24:59.860 | So the feeling of hunger,

00:25:01.220 | some people never experience hunger in their whole lives.

00:25:03.880 | It's really, really bad for them.

00:25:05.900 | It was based, I believe, on the 20th century view

00:25:10.700 | that you don't want to stress out the pancreas,

00:25:13.020 | and you try to keep insulin levels pretty steady

00:25:16.540 | and not have this fluctuation.

00:25:19.380 | What we actually found, my colleagues and I,

00:25:23.420 | across this field of longevity,

00:25:25.780 | is that when you look at, first of all, animals,

00:25:28.200 | whether it's a dog or a mouse or a monkey,

00:25:31.420 | the ones that live the longest, by far, 30% longer,

00:25:35.740 | and stay healthy, are the ones that don't eat all the time.

00:25:40.100 | It actually was first discovered

00:25:41.340 | back in the early 20th century, but people ignored it.

00:25:44.460 | And then it was rediscovered in the 1930s.

00:25:46.940 | Clive McKay did caloric restriction.

00:25:49.160 | He put cellulose in the food of rats

00:25:51.940 | so they couldn't get as many calories even though they ate,

00:25:54.580 | and those rats lived 30% longer.

00:25:57.100 | But then it went away, and then it came back in the 2000s

00:26:00.660 | in a big way when a couple of things happened.

00:26:02.660 | One is that my lab and others showed

00:26:05.520 | that there are longevity genes in the body

00:26:08.820 | that come on and protect us from aging and disease.

00:26:11.960 | The group of genes that I work on are called sirtuins.

00:26:13.940 | There's seven of them.

00:26:15.420 | And we showed in 2005 in a science paper

00:26:18.620 | that if you have low levels of insulin

00:26:22.340 | and another molecule called insulin-like growth factor,

00:26:25.780 | those low levels turn on the longevity genes.

00:26:28.780 | One of them that's really important is called SIRT1.

00:26:32.120 | But by having high levels of insulin all day,

00:26:35.340 | being fed means your longevity genes are not switched on.

00:26:39.220 | So you're falling apart.

00:26:40.300 | Your epigenome, your information

00:26:42.500 | that keeps your cells functioning over time

00:26:44.140 | just degrades quickly.

00:26:45.180 | Your clock is ticking faster by always being fed.

00:26:48.940 | The other thing that I think might be happening

00:26:53.260 | by always having food around

00:26:54.860 | is that it's not allowing the cell to have periods of rest

00:27:00.300 | and reestablish the epigenome.

00:27:03.300 | And so it also is accelerating in that direction.

00:27:06.680 | There's plenty of other reasons as well

00:27:09.080 | that are not as profound,

00:27:10.060 | such as having low levels of glucose in your body

00:27:14.260 | will trigger your major muscles in your brain

00:27:17.020 | to become more sensitive to insulin

00:27:19.660 | and suck the glucose out of your bloodstream,

00:27:21.640 | which is very good.

00:27:22.740 | You don't want to have glucose flowing around too much.

00:27:25.540 | And that will ward off type 2 diabetes.

00:27:27.900 | - So hunger, of course, is associated with low blood glucose

00:27:32.260 | and low insulin.

00:27:34.100 | Do you think there's anything

00:27:35.180 | about the subjective experience of hunger itself

00:27:38.060 | that could be beneficial for longevity?

00:27:40.260 | - Yeah, I do.

00:27:42.140 | Though you get used to the feeling of not eating.

00:27:46.740 | So I'm kind of screwed that way.

00:27:49.180 | - It's like cold water.

00:27:50.100 | You eventually adapt.

00:27:51.460 | - You get used to it, unfortunately.

00:27:53.980 | But there are some studies that are being done

00:27:55.820 | at the National Institutes of Health

00:27:57.460 | that are able to simulate the effect of hunger,

00:28:00.780 | but still provide the calories.

00:28:02.420 | And it's looking like there's a small component

00:28:04.720 | that's due to hunger.

00:28:05.980 | But most of it actually is because you've got these periods

00:28:09.260 | of not being fed,

00:28:10.300 | and then the body turns on these defensive genes.

00:28:12.740 | There's a really interesting experiment

00:28:15.300 | that was published maybe a couple of years ago

00:28:17.220 | by Rafael de Carbo down at the NIH.

00:28:20.060 | What he did was he took over 10,000 mice

00:28:22.080 | and gave them different combinations

00:28:24.140 | of fat, carbohydrate, protein.

00:28:26.740 | And he was trying to figure out what was the best combination.

00:28:29.980 | And then he also cleverly had a group,

00:28:32.700 | well, two groups, one that was fed all the time

00:28:35.060 | or ate as much as they wanted.

00:28:37.260 | And the other group was only given food for an hour a day.

00:28:40.500 | And it turns out they ate roughly

00:28:41.660 | the same amount of calories.

00:28:43.060 | 'Cause of course in an hour, they're stuffing their faces.

00:28:46.700 | It turns out it didn't matter what diet he gave them.

00:28:49.780 | It was only the group that ate within that window

00:28:51.620 | that lived longer and dramatically longer.

00:28:53.940 | So my conclusion is,

00:28:56.020 | and mice are very similar to us metabolically.

00:28:58.020 | I think that tells us that it's not as important

00:29:00.460 | what you eat, it's when you eat during the day.

00:29:02.860 | - What is the protocol that people can extrapolate

00:29:06.220 | from that?

00:29:07.060 | Or maybe I should just ask you,

00:29:09.100 | what is your protocol for when to eat

00:29:12.340 | and when to avoid food?

00:29:14.100 | Do you fast, do you ever fast longer than 24 hours?

00:29:18.600 | What do you do?

00:29:19.500 | And what do you think is a good jumping off place

00:29:21.660 | if people want to explore this as a protocol?

00:29:23.940 | - Well, if there's one thing I could say,

00:29:26.060 | if I would say definitely try to skip a meal a day,

00:29:29.700 | that's the best thing.

00:29:30.740 | - Does it matter which meal?

00:29:32.060 | Or are they essentially equivalent?

00:29:33.140 | - Well, as long as it's at the end

00:29:35.020 | or the beginning of the day,

00:29:36.180 | because then you add that to the sleep period

00:29:38.660 | where you're hopefully not eating.

00:29:40.280 | - I think that that's an excellent point.

00:29:41.700 | I realize it's a simple one,

00:29:43.040 | but I think it's an excellent one.

00:29:44.040 | 'Cause I think one of the things that people struggle

00:29:46.160 | with the most is knowing when and how to initiate

00:29:49.620 | this so-called intermittent fasting.

00:29:51.820 | And the middle of the day obviously is not tacked

00:29:54.140 | to the sleep cycle in the same way.

00:29:55.520 | So it's much harder as well for many people.

00:29:59.020 | - Yeah. - Yeah.

00:29:59.920 | - Well, I'll tell you what I do.

00:30:01.600 | I skip breakfast.

00:30:02.760 | I have a tiny bit of yogurt or olive oil

00:30:04.940 | because the supplements I have need to be dissolved in it.

00:30:08.260 | And then I go throughout the whole day

00:30:09.700 | as I'm doing right now here with this glass of water here.

00:30:13.820 | I'm just keeping myself filled with liquids.

00:30:15.900 | And so I don't feel hungry.

00:30:17.360 | Beware that the first two to three weeks

00:30:21.020 | when you try that, you will feel hungry.

00:30:22.820 | And you also have a habit of wanting to chew on something.

00:30:26.180 | There's a lot of physical parts to it,

00:30:28.240 | but try to make it through the first three weeks

00:30:30.180 | and do without breakfast or do without dinner.

00:30:33.200 | And you'll get through it.

00:30:34.860 | And I did that for most of my life actually,

00:30:38.280 | mainly because I wasn't hungry in the morning.

00:30:40.680 | Some people are very hungry in the morning

00:30:42.400 | and they may wanna consider skipping dinner instead.

00:30:45.180 | But I will go throughout the whole day.

00:30:47.060 | I don't get the crashes of the high glucose

00:30:49.980 | and the low glucose.

00:30:51.780 | Anyone who goes, "Oh man, it's three o'clock.

00:30:53.700 | "I'm gonna need a sleep."

00:30:55.180 | If you do what I do, you will not experience that anymore.

00:30:58.500 | Because what my body does

00:30:59.720 | is it regulates blood sugar levels naturally.

00:31:02.880 | My liver is putting out glucose when it needs to,

00:31:05.080 | and it's very steady

00:31:06.540 | and gives me pure focus throughout the day.

00:31:08.260 | And I don't even have to think about lunch.

00:31:10.060 | I'm just powering through.

00:31:11.740 | At dinner, I love food as much as anybody.

00:31:14.580 | So I will eat a regular, pretty healthy meal.

00:31:18.980 | I'll try to eat mostly vegetables.

00:31:20.620 | I can eat some fish, some shrimp.

00:31:23.380 | I rarely will eat a steak.

00:31:25.980 | In fact, my microbiome is so adapted to my diet.

00:31:29.300 | Now, if I eat a steak, it will not get digested very well.

00:31:32.060 | I'll feel terrible.

00:31:33.820 | - If I don't eat a steak, I feel terrible.

00:31:35.740 | (laughs)

00:31:36.980 | Argentine lineage.

00:31:38.060 | Well, we can talk about that some other time.

00:31:39.780 | - Well, everybody's different.

00:31:40.980 | I mean, that's the other thing.

00:31:42.220 | What works for me may not be perfect for you.

00:31:43.880 | And we do have to measure things to know what's working.

00:31:46.680 | I rarely eat dessert.

00:31:48.820 | I gave up dessert and sugar when I turned 40.

00:31:53.140 | And occasionally, I'll steal a bit of dessert

00:31:55.580 | 'cause it doesn't hurt if you steal it, right?

00:31:57.860 | But other than that, I avoid sugar,

00:32:00.460 | which includes simple carbohydrates,

00:32:03.340 | bread I try to avoid.

00:32:05.020 | I've actually noticed, this is just a side note.

00:32:08.060 | I used to get buildup of plaque pretty easily.

00:32:10.260 | And every time I went to the dentist,

00:32:11.340 | they'd have to scrape it off.

00:32:12.260 | And I even bought tools to scrape it off

00:32:13.620 | 'cause it was driving me nuts.

00:32:15.780 | I don't get plaque anymore.

00:32:17.020 | And I think it's because of my diet.

00:32:18.940 | I don't have those sugars in my mouth

00:32:20.380 | that the bacteria feed on

00:32:21.380 | and then form the biofilm on the teeth.

00:32:24.100 | Much better breath, by the way.

00:32:25.660 | - That's a benefit.

00:32:28.420 | So do you ever fast longer than this?

00:32:31.540 | It sounds like if you go to bed,

00:32:35.220 | well, you tend to stay up late, I know,

00:32:36.820 | because I get texts from you at like two in the morning,

00:32:39.620 | my time, which means you're out very late

00:32:42.580 | and up early as well.

00:32:43.860 | But assuming that people go to sleep

00:32:46.000 | sometime around 11, 30, or 12, plus or minus an hour,

00:32:50.240 | and wake up sometime around 7 a.m.,

00:32:52.200 | plus or minus 90 minutes,

00:32:54.220 | you're eating more or less on a,

00:32:57.680 | it sounds like some like 20 hours of fasting,

00:33:00.940 | four hours of eating, or 16 hours of fasting,

00:33:03.220 | and eight hours of food intake, et cetera.

00:33:05.980 | But do you ever do longer fasts,

00:33:07.860 | like 48 hours or 72 hours or week-long fasts?

00:33:11.420 | - Occasionally I do.

00:33:12.540 | So my typical day,

00:33:14.340 | I would only eat within a two-hour window.

00:33:16.360 | Just usually I'm either eating out or-

00:33:18.860 | - So you're 22 too.

00:33:20.180 | - Yeah, yeah, but I love, well-

00:33:23.080 | - And if you exercise, do you feel like,

00:33:25.000 | then you just power through

00:33:25.960 | and maintain that fasted state?

00:33:27.820 | - Absolutely, I can exercise,

00:33:29.240 | and now my body's so used to it,

00:33:30.660 | I don't feel like I need food after exercising, I used to.

00:33:33.560 | But have I gone longer?

00:33:36.480 | Yes, but not very often.

00:33:38.000 | I find it quite difficult to go more than 24 hours.

00:33:42.200 | But when I do it, maybe it's once a month,

00:33:43.920 | I'll go for two days.

00:33:45.240 | After two, and actually even better,

00:33:48.120 | if you go for three days without eating,

00:33:50.020 | it kicks in even greater longevity benefits.

00:33:55.020 | So there's a system called the autophagy system,

00:33:57.820 | which digests old and misfolded proteins in the body.

00:34:01.660 | And there's a natural cleansing

00:34:02.940 | that happens when you're hungry.

00:34:04.880 | Macro-autophagy, its name is.

00:34:06.760 | But a good friend of mine, Anna Maria Cuervo,

00:34:09.260 | at Albert Einstein College of Medicine,

00:34:11.200 | discovered a deep cleanse called the chaperone-mediated

00:34:14.320 | autophagy, which kicks in day two, day three,

00:34:18.060 | which really gets rid of the deep proteins.

00:34:21.680 | And what excites me is she just put out a big paper

00:34:24.520 | that said if you trigger this process in an old mouse,

00:34:28.900 | it lives 35% longer.

00:34:31.160 | - Wow.

00:34:32.000 | - Yeah, so it's a big deal.

00:34:32.960 | If I could go longer, I would.

00:34:34.600 | But I just find that with my lifestyle,

00:34:36.440 | and I'm going always day 110%, I need to eat

00:34:41.240 | at least once a day, unfortunately.

00:34:42.920 | - One more practical question,

00:34:44.100 | then a mechanistic question related to this.

00:34:46.060 | The practical question is when you are fasting,

00:34:48.960 | regardless of how long, I know you're ingesting fluids

00:34:51.800 | like water and presumably some caffeine.

00:34:54.280 | I heard you had several or more espresso today,

00:34:58.180 | which is impressive.

00:35:00.620 | But are you also ingesting electrolytes?

00:35:04.800 | Like I know some people get lightheaded,

00:35:06.520 | they start to feel shaky when they fast,

00:35:08.820 | and that the addition of sodium to their water

00:35:11.480 | or potassium, magnesium is something that's becoming

00:35:14.880 | a little more in vogue now.

00:35:16.080 | Is that something that you do

00:35:17.120 | or that you see a need for people to do?

00:35:19.420 | - Well, it makes sense, but I haven't had a need to do it.

00:35:22.500 | So I don't, I just, I drink tea during the day

00:35:26.040 | and coffee when I'm first awake and I don't get the shakes.

00:35:29.480 | So, you know, I don't fix what's not broken.

00:35:33.140 | And I do add things to my protocol

00:35:35.200 | that I think will improve me and avoid those things,

00:35:38.300 | of course, that won't.

00:35:39.400 | But yeah, because I don't have a need for it,

00:35:42.320 | I don't try it.

00:35:43.300 | But it does make sense, especially if you've had a big night

00:35:45.980 | the night before, you probably want to supplement with that.

00:35:49.060 | But I think there's fair amount of good stuff

00:35:52.040 | in tea and coffee as it is.

00:35:54.420 | - Okay, so then the mechanistic question is,

00:35:57.300 | you've told us that there's ample evidence

00:36:00.880 | that keeping your blood sugar low for a period of time,

00:36:03.840 | each 24 hours, can help trigger some of these

00:36:07.100 | pro-longevity anti-aging mechanisms.

00:36:11.360 | And that extending them out two or three days

00:36:13.900 | can trigger yet additional mechanisms

00:36:16.880 | of gobbling up of dead cells and things of that sort.

00:36:21.880 | How is it that blood glucose triggers these mechanisms?

00:36:25.780 | 'Cause we've said, okay, remove glucose

00:36:27.340 | and things get better.

00:36:29.120 | You've talked before, maybe we could talk more now

00:36:32.180 | about some of the underlying cellular

00:36:33.740 | and genetic mechanisms, things like the sirtuins.

00:36:36.140 | But how are glucose and the sirtuins

00:36:38.020 | actually tethered to one another mechanistically?

00:36:40.980 | - Yeah, there's a really good question.

00:36:43.220 | That proves you're a scientist, or a world leading on.

00:36:47.340 | So what we now know is that these longevity pathways,

00:36:51.540 | we call them, these longevity genes, talk to each other.

00:36:54.260 | And we used to say, oh, my longevity gene's

00:36:55.900 | more important than yours, it was ridiculous.

00:36:58.160 | 'Cause they're all talking to each other,

00:36:59.080 | you pull one lever and the other one moves.

00:37:01.540 | And the way to think of it is that there are systems

00:37:03.260 | set up to detect what you're eating.

00:37:05.460 | So the sirtuins will mainly respond to sugar and insulin.

00:37:10.460 | And then there's this other system called mTOR,

00:37:13.900 | which is sensing how much protein or amino acids

00:37:17.020 | are coming into your body.

00:37:18.540 | And they talk to each other, we can pull one

00:37:20.240 | and affect the other and vice versa.

00:37:22.500 | But together, when you're fasting,

00:37:24.520 | you'll get the sirtuin activation,

00:37:27.360 | which is good for you.

00:37:28.780 | And you'll also, through lack of amino acids,

00:37:31.660 | particularly three of them, leucine, isoleucine, valine,

00:37:35.140 | the body will downregulate mTOR.

00:37:37.380 | And it's that up sirtuin, down mTOR,

00:37:40.100 | that is hugely beneficial and turns on

00:37:42.580 | all of the body's defenses, chewing up the old proteins,

00:37:46.500 | improving insulin sensitivity, giving us more energy,

00:37:49.180 | repairing cells, all of that.

00:37:51.540 | And so these two pathways, I think,

00:37:53.120 | are the most important for longevity.

00:37:55.200 | - So interesting, you mentioned leucine.

00:37:57.860 | Within the resistance training/bodybuilding/fitness

00:38:02.460 | community, leucine gets a lot of attention

00:38:04.440 | because there are longstanding debates

00:38:06.540 | about how much protein one needs per day

00:38:08.800 | and how much one can assimilate at each meal.

00:38:10.700 | It makes for many YouTube videos and not much else, frankly.

00:38:15.700 | However, it's clear that because of leucine's effects

00:38:18.980 | on the mTOR pathway, that there are many people,

00:38:22.540 | not just people in these particular fitness communities,

00:38:24.980 | that are actively trying to ingest more leucine

00:38:28.200 | on a regular basis in order to maximize their wellness

00:38:32.660 | and fitness, and in some cases, muscle growth,

00:38:34.900 | but also just wellness.

00:38:36.740 | But what I interpret your last statement to mean

00:38:39.720 | is that leucine, because it triggers cellular growth,

00:38:42.980 | is actually pro-aging in some sense, is that right?

00:38:47.980 | - Well, it could be, that's what the evidence suggests.

00:38:50.420 | And again, it goes back to the debate,

00:38:52.260 | should you supplement with growth hormone or testosterone,

00:38:55.320 | all of these activities will give you immediate benefits.

00:39:00.140 | You'll bulk up more, you'll feel better immediately.

00:39:04.380 | But based on the research,

00:39:06.180 | it's at the expense of long-term health.

00:39:08.580 | So my view of longevity, the way I treat my body,

00:39:12.380 | is I don't burn both candles.

00:39:15.180 | I have one end of the candle lit.

00:39:16.940 | I'm very careful, I don't blow on it.

00:39:19.860 | But I also do enough exercise that I'm building up my muscle,

00:39:23.260 | but I'm not huge.

00:39:24.460 | Anyone who's seen me knows

00:39:26.460 | that I'm not a professional bodybuilder.

00:39:29.300 | But I tried to actually, here's the key,

00:39:31.700 | and I haven't said this publicly that I can remember,

00:39:34.400 | I pulse things so that I get periods of fasting,

00:39:37.660 | and then I eat, then I take a supplement,

00:39:40.480 | then I fast, then I exercise,

00:39:44.040 | and I'm taking the supplements and eating

00:39:46.940 | in the right timing to allow me to build up muscle sometimes.

00:39:50.940 | Because you can't just expect to take something constantly

00:39:55.340 | and do something constantly for it to work.

00:39:57.580 | And that's why it's taken me about 15 years

00:39:59.660 | to develop my protocol.

00:40:00.940 | And there's a lot of subtlety to it.

00:40:02.900 | - Yeah, it sounds like a very rational protocol.

00:40:05.000 | Does the name Ori Hofmeckler mean anything to you?

00:40:07.800 | - No. - Okay.

00:40:09.260 | Just briefly, I discovered Ori Hofmeckler

00:40:12.340 | about 15 years ago.

00:40:14.500 | He was in Israeli special forces.

00:40:16.840 | He's now got to be close to 70.

00:40:19.100 | Forgive me, Ori, if that number is inflated.

00:40:22.200 | He wrote a book called "The Warrior Diet,"

00:40:26.100 | which got very little attention at the time.

00:40:28.320 | But what he said was when he was in Israeli special forces,

00:40:31.840 | they rarely ate more than once per day,

00:40:34.300 | and sometimes once every second or third day.

00:40:36.700 | And this is a guy who maintains

00:40:38.460 | an incredible physical stature.

00:40:41.400 | You know, he's very lean, very strong, and very vital at,

00:40:45.840 | you know, I wouldn't say an advanced age,

00:40:48.040 | but he's getting up there,

00:40:49.060 | and he just seems to be getting better and better.

00:40:51.500 | Ori Hofmeckler was the person

00:40:53.300 | who essentially founded, if you will,

00:40:55.780 | although our ancestors founded, to be completely fair,

00:40:59.360 | the so-called intermittent fasting diet.

00:41:03.420 | He called it "The Warrior Diet,"

00:41:04.740 | and this book didn't get much attention.

00:41:06.120 | But one of the things that you just said

00:41:08.700 | really reminded me of Ori.

00:41:10.400 | I sat down with him.

00:41:11.240 | I actually went to his home and sat down with him,

00:41:12.860 | and he said, "Fasting is wonderful,

00:41:15.260 | but these pulses where you nourish the body

00:41:18.140 | or even slightly overnourish the body,

00:41:20.880 | provided they aren't too frequent,

00:41:23.180 | have a tremendous effect on vitality."

00:41:25.940 | And so I want to use that as kind of a segue

00:41:28.120 | to address this issue of vitality versus longevity,

00:41:33.120 | because here you're telling me,

00:41:35.440 | and certainly the evidence supports that, you know,

00:41:38.620 | growth hormone will make you feel better and younger,

00:41:40.580 | taking testosterone or estrogen, we should probably say.

00:41:43.100 | There are women who take hormone therapies later in life,

00:41:47.060 | who take estrogen, they experience a strong increase

00:41:49.860 | in vitality if it's done correctly.

00:41:52.180 | But there is an effect of aging the body more rapidly.

00:41:56.480 | It's sort of a second puberty, if you will.

00:41:59.380 | But this idea of restriction and then pulsing,

00:42:02.640 | not necessarily feast and famine,

00:42:04.700 | but certainly famine and feast in lowercase letters,

00:42:08.700 | there really seems to be something about that.

00:42:10.960 | So at a cellular level,

00:42:13.920 | like we kind of go back to mTOR and the sirtuins,

00:42:16.900 | how do you think that the cells might be reacting

00:42:20.480 | to this kind of lowercase feast

00:42:23.140 | and uppercase famine type protocol?

00:42:28.080 | - All right.

00:42:28.920 | Well, the pulsing, I think,

00:42:32.600 | is what you want to do is to get the cells

00:42:35.000 | to be perceiving adversity.

00:42:39.280 | 'Cause our modern life, we're sitting around,

00:42:41.160 | we're eating too much, we're not exercising,

00:42:45.660 | our cells respond.

00:42:47.040 | They go, "Hey, everything's cool, no problem."

00:42:49.440 | And they become relaxed and they turn on their defenses

00:42:52.240 | and we age rapidly.

00:42:53.200 | We can see it in the clock.

00:42:54.640 | People who exercise and eat less

00:42:56.740 | have a slower ticking clock.

00:42:58.260 | It's a fact.

00:42:59.100 | But my protocol is different than most people's

00:43:03.440 | because I am pulsing it.

00:43:05.500 | Now, first of all, let's get to why did I even think

00:43:08.240 | that might be possible?

00:43:09.180 | 'Cause I didn't read "The Warrior Diet."

00:43:11.880 | What I found in my research was that

00:43:15.680 | if we gave resveratrol, this red wine molecule

00:43:18.220 | that became well-known in the 2000s,

00:43:20.840 | if we gave it to mice their whole lifespan,

00:43:25.120 | they were protected against a high-fat diet,

00:43:27.360 | which we call the Western diet.

00:43:29.000 | They had lean organs.

00:43:30.840 | They lived slightly longer, but not a lot.

00:43:33.840 | And if we gave them a high-fat diet without resveratrol,

00:43:37.880 | they actually lived a lot shorter.

00:43:40.520 | So resveratrol protected them against the high-fat diet.

00:43:43.420 | We gave it to them on a normal diet.

00:43:44.820 | They just ate it when they wanted

00:43:46.500 | and there wasn't much effect.

00:43:48.520 | This is what's not known,

00:43:49.740 | though it's in the supplemental data of the paper

00:43:51.780 | that nobody ever reads.

00:43:53.140 | The mice that were given resveratrol every second day

00:43:57.060 | on a normal diet lived dramatically longer

00:44:00.200 | than any other group.

00:44:01.380 | So people out there, you know, my critics say,

00:44:05.020 | "Oh, resveratrol didn't extend the lifespan

00:44:06.820 | "of mice on a normal diet.

00:44:08.640 | "Therefore, it's not aging.

00:44:10.500 | "It's just protecting against a high-fat diet."

00:44:12.720 | Well, look at the supplemental data, please.

00:44:15.200 | If you give it to the mice every other day,

00:44:17.880 | we had mice living over three years.

00:44:19.940 | - Wow, that's a long time.

00:44:21.620 | I have got many, many mice in my ownership

00:44:25.660 | at my lab at Stanford,

00:44:27.020 | and that's a very long life for a mouse.

00:44:29.520 | - It was by far.

00:44:30.580 | And so it was a long lifespan extension.

00:44:33.940 | And what that told me is that probably

00:44:37.020 | you don't wanna be taking a supplement every day.

00:44:40.340 | You can take it either every other day

00:44:42.160 | or give your body a rest.

00:44:43.740 | And I do the same with my meals.

00:44:45.500 | I rest during the day,

00:44:46.740 | and then I give a nutritious dinner to my body

00:44:49.920 | and then give it a rest.

00:44:50.900 | Same with exercise.

00:44:51.980 | And then I try to time it,

00:44:53.420 | 'cause there are times when I'm taking the drug metformin,

00:44:56.500 | which mimics low energy.

00:44:58.420 | For those of you who don't know,

00:45:00.100 | metformin is a drug given to type 2 diabetics

00:45:02.340 | to bring down their blood sugar levels.

00:45:04.420 | But it's been found that looking at tens of thousands

00:45:06.580 | of veterans and others,

00:45:08.460 | that those two type 2 diabetics live longer

00:45:10.600 | than people that don't even get type 2 diabetes.

00:45:12.420 | So it's a longevity drug.

00:45:14.940 | Right now, you have to get it from your doctor in the US.

00:45:17.660 | In most other countries,

00:45:18.860 | you can just get it over the counter.

00:45:20.840 | And you're protected, it looks like,

00:45:23.780 | based on epidemiological data,

00:45:26.740 | cancer, heart disease, frailty.

00:45:31.060 | What else? Dementia.

00:45:32.500 | So I take metformin.

00:45:34.620 | - In addition, you take metformin and your fasting each day.

00:45:37.980 | So when do you take it relative to the fasting?

00:45:39.980 | - Yeah, I always take metformin in the morning,

00:45:44.060 | along with the resveratrol,

00:45:46.460 | because, for a number of reasons,

00:45:48.420 | but mainly because my body responds better,

00:45:52.780 | and I've been measuring my body for 12, 13 years.

00:45:55.440 | But here's the thing, if I'm going to exercise that day,

00:45:59.640 | I will skip the metformin.

00:46:02.060 | And a lot of people who do pay attention

00:46:04.460 | to this kind of thing

00:46:06.220 | think that they should stop taking metformin

00:46:08.020 | 'cause they're never going to get muscle,

00:46:09.520 | or it's going to affect their ability to build up muscle.

00:46:12.360 | But that's not true.

00:46:14.380 | What metformin does to you,

00:46:16.680 | it actually just reduces your ability to have stamina,

00:46:20.580 | because it's inhibiting your body's ability to make energy.

00:46:23.480 | And so what happens is, when you're on metformin,

00:46:26.740 | you do fewer reps.

00:46:28.760 | But guess what?

00:46:29.600 | These muscles that you do build up on metformin

00:46:32.460 | have the same strength and have much lower inflammation

00:46:35.100 | and other markers of aging.

00:46:37.620 | You just won't have that extra 5% size of muscles.

00:46:41.900 | So if you want large muscles, don't take metformin,

00:46:44.800 | and you'll be fine during your exercise.

00:46:48.020 | But for me, I'm not trying to get giant.

00:46:50.740 | I want strong muscles,

00:46:51.660 | and I want to live longer and healthier.

00:46:53.900 | So I just try to time it

00:46:56.820 | so that I get the most reps out of my exercise regime.

00:47:01.360 | But sometimes in scientific literature,

00:47:04.860 | it's worth bringing this up.

00:47:06.720 | If there's a 5% difference in a graph,

00:47:09.200 | then either the press release or some reporter will say,

00:47:13.440 | "Oh my goodness, big difference.

00:47:14.920 | "5% can't take metformin during exercise."

00:47:17.840 | That's the headline.

00:47:19.020 | And then you go in and it's barely significant,

00:47:21.540 | and the graph is distorted

00:47:22.680 | because they've changed the axes to make it look bigger.

00:47:25.960 | And now it's become a myth

00:47:28.160 | that metformin greatly inhibits your ability to exercise,

00:47:31.260 | which is not true.

00:47:32.800 | But in an abundance of caution,

00:47:34.200 | I skip my metformin on days I'm going to exercise.

00:47:37.460 | And not only that, I'm one of the 20% of people

00:47:39.580 | that has a stomach sensitivity to it.

00:47:42.600 | So if I'm not feeling great that day,

00:47:44.320 | I don't take it either.

00:47:45.540 | - You mentioned metformin is available only by prescription

00:47:48.160 | from a doctor, at least in the US.

00:47:50.640 | Berberine is a substance that comes from tree bark,

00:47:53.360 | who I also learned about many years ago from Ori.

00:47:56.260 | He said, "If ever I'm going to overeat

00:47:59.240 | "like a Thanksgiving meal or something, I take berberine."

00:48:02.640 | Those were his words, and I tried it.

00:48:04.520 | And what's remarkable about berberine

00:48:06.240 | is that you can eat enormous quantities of food

00:48:09.560 | and not feel as if you've eaten enormous quantities of food.

00:48:12.380 | I'm not necessarily recommending people do this,

00:48:14.740 | but what I noticed was if I took berberine,

00:48:18.760 | which my understanding is it works very similarly

00:48:21.200 | to metformin, works on the AMPK pathway,

00:48:23.720 | the mTOR pathway, et cetera,

00:48:25.160 | that if I didn't ingest food in particular carbohydrates,

00:48:29.900 | I would feel a little dizzy and kind of get a headache,

00:48:32.060 | like almost hypoglycemic.

00:48:34.280 | What are your thoughts on berberine

00:48:36.560 | as an alternative to metformin?

00:48:38.840 | And are there any cautionary notes?

00:48:41.060 | I mean, obviously people should talk to their doctor

00:48:42.780 | before adding or subtracting anything from their life,

00:48:45.140 | including breath work or anything that comes up.

00:48:49.360 | But with all that set aside,

00:48:52.040 | what are your thoughts about berberine

00:48:53.680 | and timing of low blood sugar and these sorts of things?

00:48:57.760 | - Right.

00:48:58.600 | Well, before I had access to metformin,

00:49:00.440 | I was taking berberine.

00:49:01.800 | It's often known as the poor man's metformin.

00:49:04.180 | - He just called me poor.

00:49:06.840 | - Women can take it too.

00:49:08.560 | So the thing with berberine, and we've studied it in my lab,

00:49:11.440 | it is effective at boosting energetics in the body,

00:49:15.080 | just like AMPK and metformin does.

00:49:19.060 | And we've actually given it to rats and mice

00:49:21.720 | and seen that they are very healthy,

00:49:23.080 | especially on a high fat diet.

00:49:24.580 | So I think it's likely to be good.

00:49:27.680 | There are some human studies that exist,

00:49:29.680 | clinical trials showing that it increases

00:49:31.420 | insulin sensitivity.

00:49:32.360 | You have to take high doses.

00:49:33.480 | - Which is a good thing, right?

00:49:34.760 | - Yeah.

00:49:35.600 | - I think when people hear insulin sensitivity,

00:49:36.740 | sometimes people think, oh, well, that's bad, right?

00:49:39.160 | No, but you want your cells to be insulin sensitive.

00:49:41.200 | You don't want a lot of blood sugar floating around

00:49:43.480 | that can't be sequestered into cells.

00:49:45.480 | - Exactly.

00:49:46.320 | - This is anti type two diabetes.

00:49:49.200 | And so that this berberine does have wonderful effects

00:49:52.920 | on the metabolism of animals and in some clinical trials

00:49:56.480 | on dozens of people it's been tested.

00:49:58.440 | Now there's one cautionary tale, which just came up,

00:50:01.880 | Matt Kaeberlein's lab published that berberine

00:50:04.480 | reduced the lifespan of worms.

00:50:06.100 | But I'm not sure worms trump human clinical trials

00:50:10.200 | at this point.

00:50:11.240 | So I would say-

00:50:12.080 | - Not in my opinion, but no disrespect

00:50:13.920 | to my C. Elegans colleagues,

00:50:15.520 | or rather my colleagues that work on C. Elegans.

00:50:17.320 | - Yeah.

00:50:18.160 | Well, what I like to do is to give all the information

00:50:20.200 | people can decide what they want.

00:50:21.960 | But I would say if based on the worm data,

00:50:24.280 | I wouldn't panic just yet.

00:50:26.000 | I think berberine has been shown to be really safe in humans.

00:50:29.440 | - You mentioned resveratrol.

00:50:31.000 | I think now would be a great time to talk a little bit

00:50:33.240 | about protocols for resveratrol,

00:50:35.040 | grape seed extract, et cetera.

00:50:37.400 | Let's start with the obvious one that I know you get a lot,

00:50:40.220 | but for the record, can't I just drink red wine

00:50:45.040 | and get enough resveratrol, David?

00:50:47.960 | - You can try.

00:50:48.880 | You need to drink about 200 glasses a day.

00:50:51.600 | So I-

00:50:52.440 | - I'm sure it's been tried.

00:50:54.040 | - There are some.

00:50:55.280 | And I drink a glass of red wine a day if I get the chance.

00:51:00.040 | But any more than that, it's a lot of calories

00:51:02.240 | and your liver will get fatty and it's all bad.

00:51:04.120 | So realistically, you can only get the thousand milligrams

00:51:08.180 | that I take a day from a supplement that's pure.

00:51:13.180 | Now, there are a lot of people selling resveratrol.

00:51:14.920 | If it's not light gray or white in color, throw it away.

00:51:19.080 | The brown stuff has gone bad or is contaminated.

00:51:23.000 | And the contaminated stuff, beware, it'll cause diarrhea.

00:51:26.320 | But regular resveratrol should not do that.

00:51:28.680 | - So a thousand milligrams per day is what you do?

00:51:31.600 | - Yeah, and I have for about 15 years now.

00:51:34.840 | - And you ingest that with some fatty substance

00:51:38.400 | like olive oil or yogurt, is that right?

00:51:40.760 | - Yeah, you have to.

00:51:41.600 | And other supplements, quercetin, curcumin,

00:51:45.240 | these are crunchy things.

00:51:46.280 | They're not gonna get through your gut.

00:51:48.020 | And I'm not just making this up.

00:51:49.520 | I always base my statements on human studies.

00:51:53.040 | So we've done a lot of studies on resveratrol

00:51:55.400 | as have others since.

00:51:56.780 | And we know that from, we found out early,

00:51:59.360 | I was one of the first people to take a high dose

00:52:01.000 | for resveratrol.

00:52:02.360 | And when we included it with food,

00:52:04.680 | the levels in my blood went up fivefold.

00:52:07.480 | And so you wanna have something in there.

00:52:09.140 | If you just drink it with water,

00:52:10.120 | it's not gonna get through.

00:52:11.680 | And unfortunately, some people have done clinical trials

00:52:13.960 | without even thinking that they might need

00:52:16.020 | to dissolve it in something.

00:52:17.840 | - So are you taking this all at once in the morning

00:52:20.260 | and chasing it with some olive oil?

00:52:21.840 | Or are you dissolving it in yogurt?

00:52:24.620 | What's the specific protocol?

00:52:26.560 | - Yeah, I've been improving, perfecting what I do.

00:52:31.560 | For about 10 years, I would take some Greek yogurt,

00:52:34.980 | couple of spoonfuls, put the resveratrol on there,

00:52:37.800 | mix it around, make sure it's dissolved,

00:52:39.680 | and put that in my mouth and swallow that.

00:52:41.740 | These days, what I like to do,

00:52:42.960 | because I've realized that olive oil,

00:52:45.700 | and particularly oleic acid,

00:52:47.840 | one of the monounsaturated fatty acids,

00:52:50.420 | is also an activator of the sirtuin defenses.

00:52:54.060 | So I'm trying to ingest more oleic acid.

00:52:57.140 | So I switched to olive oil.

00:52:58.800 | What I do is I put a couple of teaspoons of olive oil

00:53:01.000 | in a glass, mix around the resveratrol

00:53:04.080 | and maybe some quercetin, a similar molecule,

00:53:07.120 | make sure it's dissolved.

00:53:08.900 | I put a little bit of vinegar.

00:53:10.480 | And if I have a basil leaf, I'll put that in.

00:53:14.240 | And it's like drinking some salad dressing, and it's great.

00:53:17.280 | - Delicious.

00:53:18.120 | That raises a question that I want to ask

00:53:22.800 | before we get to NMN and NR and vitamin B3,

00:53:27.800 | which is, by doing that,

00:53:31.040 | do you think that it breaks your fast?

00:53:33.280 | And I want to just frame this question of breaking the fast

00:53:36.420 | in a more general scientific theme.

00:53:38.680 | And I'd love your thoughts on this.

00:53:41.040 | One of the questions I get asked all the time

00:53:42.920 | is does ingesting blank break the fast?

00:53:46.160 | Does eating this or drinking this, coffee,

00:53:49.320 | if I walk in the room and someone else is eating a cracker,

00:53:51.580 | does it break my fast?

00:53:53.380 | People get pretty extreme with this.

00:53:55.000 | My sense, and please tell me if I'm wrong,

00:53:57.940 | but my sense is that it depends on the context

00:54:00.580 | of what you did the night before,

00:54:02.180 | whether or not you're diabetic, lots of things.

00:54:04.820 | So for instance, if I eat an enormous meal at midnight,

00:54:07.940 | go to sleep, wake up at 6 a.m.,

00:54:11.260 | I could imagine that black coffee

00:54:14.240 | or coffee with a little bit of cream

00:54:15.680 | might quote unquote break my fast,

00:54:17.640 | but the body doesn't have a breaking the fast switch.

00:54:20.120 | The body only speaks in the language of glucose,

00:54:22.520 | AMPK, mTOR, et cetera.

00:54:24.800 | So do you worry that ingesting these calories

00:54:28.560 | is going to quote unquote break your fast?

00:54:30.260 | And more generally, how do you think about the issue

00:54:33.120 | of whether or not you're fasting enough

00:54:34.860 | to get these positive effects?

00:54:36.600 | Because not everybody can manage on just water or just tea,

00:54:41.600 | or we should say not everybody is willing to manage

00:54:44.620 | on just water or just tea for a certain part of the day.

00:54:47.440 | - Well, my first answer is not scientific.

00:54:49.320 | It's philosophical.

00:54:50.760 | If you don't enjoy life, what's the point?

00:54:53.300 | And so I'd like a cup of coffee in the morning,

00:54:56.260 | little bit of milk, spoonful of yogurt's not gonna kill me.

00:54:59.780 | Olive oil doesn't have protein or carbs in it, not many.

00:55:04.260 | And so I'm probably not affecting those longevity pathways

00:55:07.160 | negatively, but without that, first of all,

00:55:11.580 | I wouldn't enjoy my life as much.

00:55:12.820 | Second, well, the olive oil is not as great as the yogurt,

00:55:15.240 | but I'm trying to optimize and there's no perfect solution

00:55:20.240 | to what we're doing.

00:55:21.660 | And we're still learning.

00:55:22.720 | We don't know what's optimal for me,

00:55:24.820 | let alone everybody else.

00:55:26.520 | But I'm with you.

00:55:27.460 | I don't believe that taking a couple of spoonfuls

00:55:30.100 | of something, unless it's high fructose corn syrup

00:55:33.180 | is gonna hurt you because I've now got the rest of the day

00:55:36.100 | till about eight, 9 p.m. of not eating anything.

00:55:39.440 | And I forgive myself for that.

00:55:42.620 | And there's a really good point here.

00:55:44.540 | You and I were discussing this earlier.

00:55:46.500 | The point about doing this is that you try to do your best.

00:55:52.640 | If you go from regular living to don't eat the whole day,

00:55:57.220 | you're gonna fail, like quitting smoking cold turkey.

00:56:00.300 | It's easy to chew gum and stick the patch on

00:56:02.740 | 'cause your body has to get used to all sorts of habits.

00:56:05.120 | And it's social, it's physical,

00:56:06.820 | putting stuff in your mouth, chewing,

00:56:08.640 | not just the low blood sugar levels.

00:56:10.660 | And your brain will fight it.

00:56:12.100 | Your limbic system is gonna go, hey, do it, do it, do it.

00:56:15.420 | And you're gonna have to fight it.

00:56:17.620 | But once you get through it, you'll be better.

00:56:19.900 | But you do it in stages.

00:56:22.060 | Do breakfast first, then do small lunch,

00:56:25.220 | and then eventually cut lunch out.

00:56:26.940 | Don't go cold turkey 'cause everyone knows it's a fact

00:56:30.380 | that if you try to do a strict diet right out of the gates,

00:56:33.940 | you'll almost always fail.

00:56:35.560 | - No, I think that captures the essence

00:56:39.380 | of fasting rationally and a rational approach

00:56:42.940 | to supplementation very well.

00:56:44.800 | Along the lines of supplementation,

00:56:47.820 | what about NMN, NRNB3 niacin?

00:56:52.540 | I want to know what you do.

00:56:57.380 | I also want to know what I should do.

00:56:59.640 | And I think most people want to know what they should do.

00:57:02.640 | I mean, these are molecules that impact the sirtuin pathway,

00:57:05.800 | impact the pathways that control aging

00:57:08.860 | or rates of aging in the epigenome.

00:57:10.620 | How do they do that?

00:57:12.880 | And how does one incorporate that

00:57:14.560 | into a supplementation protocol

00:57:16.940 | should they choose to do that?

00:57:18.160 | - All right.

00:57:19.240 | Well, disclaimer is that I don't recommend anything,

00:57:21.540 | but I talk about what I do.

00:57:22.940 | So a bit of scientific background.

00:57:25.160 | These sirtuin genes that we discovered first in yeast cells

00:57:27.760 | when I was at MIT and then in animals

00:57:31.020 | as I moved to Harvard in the 2000s.

00:57:33.320 | And one of my first postdocs,

00:57:35.360 | actually literally my first postdoc, Chaim Cohen,

00:57:37.740 | published a great paper just a couple of months ago

00:57:41.260 | and found that turning on the sirtuin 6 gene,

00:57:44.940 | remember the 7, number 6 gene is very potent.

00:57:47.700 | It extended the lifespan dramatically of mice

00:57:50.040 | that he engineered, both males and females, which is great.

00:57:53.180 | So what you want to do is,

00:57:55.320 | so naturally boost the activity of these sirtuins.

00:57:58.560 | They are genes, but they also make proteins.

00:58:00.560 | That's what genes typically make or encode.

00:58:03.440 | And then those proteins take care of the body

00:58:04.960 | in many different ways, as we've discussed.

00:58:07.400 | So how do you turn on these genes

00:58:09.120 | and make the proteins they make even more active?

00:58:11.560 | You want to rev up that system.

00:58:12.600 | So exercise will do it, fasting will do it.

00:58:16.560 | What about supplementation?

00:58:17.780 | Well, the first activator of the sirtuins that we discovered

00:58:21.440 | that acts on the enzyme to make it do a better job

00:58:23.840 | of cleaning up the body and protecting was resveratrol.

00:58:27.520 | We looked at thousands of different molecules,

00:58:30.320 | eventually tens of thousands.

00:58:32.040 | And the one that was the best was resveratrol in the dish.

00:58:35.840 | And then we gave it to little organisms, worms,

00:58:38.360 | and then flies and mice, eventually humans.

00:58:41.880 | And we saw that it activated that enzyme.

00:58:44.040 | So resveratrol is one way to activate it.

00:58:46.560 | You can think of it as the accelerator pedal on a car.

00:58:49.360 | It revs it up, but there's something else

00:58:52.400 | that the sirtuins need to work, and that's NAD.

00:58:56.100 | NAD is a really small molecule,

00:58:57.880 | little chemical in the body that we need for life.

00:59:00.600 | It's used by the body for chemical reactions,

00:59:03.280 | 400 different reactions in the body,

00:59:04.840 | and without it, you're dead within seconds.

00:59:07.320 | You need NAD.

00:59:09.220 | The problem that we've seen is that NAD levels decline

00:59:13.060 | as you become obese, as you get older,

00:59:16.960 | if you don't ever get hungry.

00:59:19.360 | And the body not only doesn't make enough of it,

00:59:22.700 | it's chewing it up as well.

00:59:23.920 | There's an enzyme called CD38 that Eric Verdin over at UCSF

00:59:28.920 | showed chews up, oh, he's now at the Buck Institute

00:59:32.240 | in California, chews up NAD as you get older.

00:59:35.480 | So it's a double whammy.

00:59:36.320 | You don't make as much, you chew it up,

00:59:38.520 | which is really bad because what we've shown in my lab

00:59:40.520 | and so have others is that NAD levels are really important

00:59:43.240 | for keeping those sirtuin defenses at a youthful level.

00:59:47.220 | And you can give a lot of resveratrol,

00:59:48.760 | but if you don't have the fuel,

00:59:50.360 | you're basically accelerating a car

00:59:52.520 | that doesn't have enough gas.

00:59:54.160 | So you wanna do both, and that's what I do.

00:59:55.760 | I take a precursor to NAD called NMN,

01:00:00.160 | and the body uses that to make the NAD molecule in one step.

01:00:05.160 | And so I know from measuring dozens of human beings

01:00:09.340 | that if you take NMN for the time period that I do,

01:00:13.480 | I've been taking it for years,

01:00:14.400 | but if you take it for about two weeks,

01:00:16.320 | you'll double, on average, double your NAD levels

01:00:19.500 | in the blood, okay?

01:00:20.840 | That's not public information.

01:00:22.140 | That's from clinical trials that are not yet published

01:00:24.800 | over the last two years.

01:00:26.660 | There are other ways to increase NAD levels

01:00:29.160 | in someone like me who's getting older, I'm 52 now.

01:00:31.980 | You can take NR, which is used to make NMN,

01:00:36.760 | which is used to make NAD.

01:00:38.520 | And both NMN and NR are sold by companies in the US.

01:00:45.360 | NR lacks the phosphate.

01:00:49.440 | Phosphate's a small chemical the body needs.

01:00:52.040 | You've probably heard of the atom phosphorus.

01:00:54.240 | Let's go back one step.

01:00:58.000 | How do you make NR?

01:00:59.280 | NR gets made from vitamin B3 often.

01:01:02.680 | You can also find it in milk and other foods.

01:01:05.760 | But sometimes people ask me,

01:01:06.760 | "Why don't you just take vitamin B3,

01:01:08.440 | "and won't that just force the body to make NAD?"

01:01:12.080 | And the answer is no, it doesn't work very well.

01:01:14.840 | We know this just by doing the experiment.

01:01:17.880 | But the reason I think is is that NAD is,

01:01:21.520 | I said it's a small molecule,

01:01:22.680 | but relative to vitamin B3, it's big.

01:01:25.560 | It's got those phosphates on there.

01:01:27.560 | It's got a sugar.

01:01:28.840 | It's got the vitamin B attached.

01:01:33.440 | So you've got all these components that come together

01:01:35.680 | to make this very complicated little molecule called NAD.

01:01:40.160 | And when you give NMN, it contains all three components

01:01:43.560 | that the body needs to make an AD.

01:01:45.600 | If you give NR, or just vitamin B3,

01:01:48.320 | which is an even smaller molecule,

01:01:50.080 | the body has to find these other components

01:01:51.840 | from somewhere else.

01:01:53.140 | So where do you get phosphate?

01:01:55.140 | Well, body needs it for DNA, needs it for bones.

01:01:58.520 | So high doses of something

01:02:00.880 | that requires additional phosphate

01:02:03.520 | makes me a little concerned.

01:02:05.460 | And we have compared NMN and NR head to head

01:02:07.840 | in mouse studies.

01:02:09.660 | For instance, NMN we've shown

01:02:11.880 | in a cell paper a few years ago, makes mice run further.

01:02:14.760 | Old mice can run 50% further

01:02:16.280 | 'cause they have better blood flow, better energy.

01:02:18.220 | NR at the same dose did not do that.

01:02:20.020 | In fact, it had no effect.

01:02:21.300 | - I see.

01:02:22.140 | Dosage-wise, if I were elect to take NMN in supplement form

01:02:27.480 | to increase my NAD levels and presumably slow my aging,

01:02:32.480 | how much NMN should I take?

01:02:35.240 | What's the protocol that you do?

01:02:39.120 | And are the various forms that are out there,

01:02:42.100 | are some better or some worse?

01:02:43.720 | - Well, I'm always happy to tell you what I do

01:02:47.560 | and what my father does, my 82-year-old father.

01:02:50.060 | We take a gram of NMN every day.

01:02:52.980 | - So it's a gram of resveratrol and a gram of NMN.

01:02:56.040 | - Right.

01:02:56.880 | - Okay, 1,000 milligrams.

01:02:58.040 | - Now, another important point,

01:03:02.000 | which is I'm not the same as everybody else.

01:03:04.880 | I have a different microbiome, age, sex, right?

01:03:08.380 | And so I've been measuring myself.

01:03:10.420 | And so I know if something's,

01:03:12.500 | or I think I know if something's making me better or worse

01:03:14.720 | based on measuring 45 different things.

01:03:17.900 | So I just want people to be aware

01:03:20.580 | that what I do may not perfectly work at all for others.

01:03:25.060 | But I have studied, as I said,

01:03:26.840 | dozens of people who take NMN at a gram, sometimes two grams.

01:03:31.840 | And I know by looking at all those people

01:03:34.860 | that without any exceptions,

01:03:36.900 | that if you do what I do, your NAD levels go up

01:03:39.980 | by about twofold or more.

01:03:42.020 | And so I do that every day, the 1,000 milligrams.

01:03:44.480 | Now, people sell it.

01:03:45.840 | Now, I never get into brands and all that.

01:03:48.220 | First of all, I don't have the time to measure products.

01:03:52.100 | I don't know.

01:03:53.280 | Though I should say, I do want to say,

01:03:55.000 | I'm working on a solution for people to know what works

01:03:59.300 | and what's real and what isn't, but I'm not there yet.

01:04:02.320 | And in the meantime, I would say,

01:04:04.340 | if you do want to buy this,

01:04:06.540 | let's say you want to buy NMN,

01:04:08.140 | look for a company that is well-established,

01:04:10.760 | that has high levels of quality control.

01:04:13.900 | Look for three letters, GMP,

01:04:16.260 | which is good manufacturing practices.

01:04:19.140 | And so that means they make it

01:04:20.260 | under a certain level of quality control.

01:04:22.280 | You're not going to find iron filings in there,

01:04:25.500 | and it probably has the stuff in it that they say it does.

01:04:29.060 | So that's all I can say right now.

01:04:32.580 | I'm working on something that's going to be much more helpful.

01:04:34.980 | But overall, make sure it's white, crystalline, NMN,

01:04:39.580 | and that to me, it tastes like burnt popcorn.

01:04:42.460 | - You crack open the capsules,

01:04:43.780 | and you'll take a little sample

01:04:44.920 | to make sure it tastes like burnt popcorn.

01:04:46.780 | - Well, when I'm making my capsules, I'll taste it,

01:04:50.460 | and I do a lot of quality control on the stuff that I take.

01:04:53.560 | - Do you take that gram all at once with the resveratrol,

01:04:56.060 | or do you take it spread throughout the day?

01:04:58.580 | - It's all in the morning for those things.

01:05:01.540 | So if I take metformin, it's NMN,

01:05:04.820 | and there is resveratrol all together.

01:05:06.620 | And there's a good reason for that.

01:05:08.380 | It's all scientific, I try to be.

01:05:10.400 | The levels of NAD go up in the morning

01:05:13.780 | in our bodies naturally.

01:05:14.740 | Our bodies actually have a cycle of NAD.

01:05:16.400 | It's not steady.

01:05:17.240 | - It's circadian.

01:05:18.080 | - It's circadian.

01:05:18.900 | In fact, NAD controls your clock.

01:05:22.220 | This was shown by Shin, MI, and colleagues

01:05:24.220 | in a nice science paper about a decade ago,

01:05:27.060 | that if you disrupt the NAD cycle,

01:05:28.860 | which is controlled by the sirtuin gene that we worked on,

01:05:33.020 | that is what's telling your body, oh, it's time to eat,

01:05:35.860 | it's time to go to sleep.

01:05:37.340 | And if you take the NMN late at night, for example,

01:05:41.260 | you can disrupt your circadian rhythms.

01:05:43.320 | - Interesting.

01:05:44.160 | - Conversely, when I travel

01:05:45.860 | and I want to reset my clock to the time zone,

01:05:48.620 | I will take a boost of NMN in the morning and I feel great.

01:05:53.620 | - Does this protocol for you,

01:05:56.520 | does it produce any immediate effects

01:06:00.140 | of increased energy, et cetera?

01:06:01.940 | You mentioned that one would, if it's right for them,

01:06:05.840 | would have to take it for at least two weeks

01:06:08.180 | to start to see the NAD levels increase.

01:06:10.140 | At that point, when NAD levels increase,

01:06:13.580 | could one possibly expect an increase

01:06:16.020 | in overall energy focus, et cetera?

01:06:20.480 | I realize we're not making promises here,

01:06:21.980 | but I'm just wondering whether or not the only measure

01:06:24.020 | of whether or not this protocol is working

01:06:25.860 | is whether or not you die at age blank or blank plus 20.

01:06:30.820 | And of course, once you're dead,

01:06:33.900 | you can't really know if you would have lived longer

01:06:36.580 | if you'd done something differently and vice versa.

01:06:38.580 | - Sure.

01:06:39.420 | Well, there was a study, again by Shin Amai,

01:06:41.220 | my good friend at Washington University in St. Louis,

01:06:43.920 | that showed that it improves,

01:06:46.660 | remember, this insulin sensitivity, which is a good thing.

01:06:50.460 | But you can't know your insulin sensitivity

01:06:52.160 | unless you're measuring a glucose,

01:06:53.860 | have a glucose monitor on your arm.

01:06:55.140 | - Do you have one on right now?

01:06:56.340 | - No.

01:06:57.780 | No, I used to.

01:06:58.740 | I learned a lot.

01:06:59.560 | Last time I saw you had this thing.

01:07:01.060 | It looks like a small leech, not a large leech,

01:07:04.220 | and it was measuring your blood glucose.

01:07:06.220 | - They're very informative

01:07:07.340 | because you learn what your body reacts to

01:07:09.520 | and grapes were really bad.

01:07:11.420 | Rhonda Patrick agrees with that.

01:07:14.120 | But the issue was what?

01:07:18.220 | Where were we, Andrew?

01:07:19.660 | - The issue was whether or not

01:07:20.580 | you can expect any immediate effects

01:07:22.900 | on energy, vitality, focus, just even subjective.

01:07:26.500 | - So what do you feel is the question?

01:07:28.080 | - And anecdotally,

01:07:29.660 | 'cause I've been taking this for a long time,

01:07:31.020 | if I don't take it, I start to feel 50 years old.

01:07:33.140 | It's horrible.

01:07:33.980 | I can't think straight.

01:07:35.800 | It may be placebo, but who knows?

01:07:38.900 | But what we're doing now are very careful clinical trials.

01:07:41.500 | We've done the safety for two years,

01:07:43.340 | and we're now treating elderly patients

01:07:45.740 | at Harvard Medical School with some wonderful colleagues.

01:07:49.100 | And those people are actually going to be,

01:07:51.380 | and currently in MRIs,

01:07:53.780 | so you can measure the energetics and the NAD levels

01:07:57.660 | in their legs as they exercise in real time.

01:08:00.840 | And that will tell us if what we see in the mice,

01:08:03.440 | this increased endurance, actually works.

01:08:05.820 | In the meantime, it's fun to talk about anecdotes.

01:08:07.860 | I have a number of athlete friends,

01:08:10.500 | some of which have increased their,

01:08:12.700 | lowered their time in marathons, for example.

01:08:15.820 | There's a good friend of ours in our circle

01:08:18.860 | that is winning marathons at age 50 now,

01:08:21.820 | and he attributes that to the protocol that he's on.

01:08:24.580 | - Interesting.

01:08:25.420 | I haven't started taking NMN,

01:08:26.860 | but I'm planning to do that when my next birthday arrives,

01:08:30.100 | which is in a couple months.

01:08:31.400 | But I do experiments on my sister and have for years,

01:08:34.280 | I have a sister who's three years older than I am

01:08:37.300 | who is very enthusiastic about these protocols.

01:08:40.160 | And I'll tell you that after reading your book,

01:08:43.080 | I started purchasing for her

01:08:45.000 | and giving her an NMN supplement.

01:08:47.200 | And she claims, and I believe her,

01:08:50.140 | she has a quite sensitive system

01:08:51.640 | and she's very tuned into it.

01:08:52.940 | She feels far and away better when she takes it

01:08:56.400 | as opposed to when she doesn't.

01:08:57.660 | And I've done the control experiment of removing her supply

01:09:01.200 | and then giving it back to her and this kind of thing.

01:09:03.360 | So that's my other laboratory.

01:09:06.000 | This is what younger brothers do to older sisters.

01:09:10.100 | I have a question about something that if it has no relevance

01:09:12.600 | we can just treat it as a speed bump and then move right on.

01:09:16.100 | And the artificial sweeteners, these things that,

01:09:18.820 | or I should say non-glucose increasing sweeteners.

01:09:23.020 | So you've got stevia, which is a plant basically,

01:09:26.060 | and then you've got sucralose and aspartame

01:09:29.140 | and all these things.

01:09:30.620 | There is some evidence that I know we're both aware of,

01:09:33.300 | they've been published in quite reputable journals

01:09:35.380 | showing that they can disrupt the gut microbiome

01:09:38.660 | in certain cases, in particular saccharin,

01:09:40.580 | the one that basically nobody uses anymore.

01:09:42.840 | And it's questionable as to whether or not stevia

01:09:45.500 | has the same negative effects, et cetera.

01:09:47.020 | That's not what this is about.

01:09:48.160 | But in terms of the sensation of,

01:09:51.860 | or the perception of sweet taste,

01:09:55.060 | is that itself a possible detriment to these pro-longevity,

01:09:59.880 | forgive me for using the term, the pathways?

01:10:04.300 | If I were to drink a Diet Coke during a fast,

01:10:07.200 | am I somehow disrupting this?

01:10:08.620 | And I'm asking this question

01:10:09.500 | because I get asked this question a lot.

01:10:11.660 | - Well, there may be small effects.

01:10:13.800 | I don't think they're worth worrying about.

01:10:16.500 | Joe Rogan laughed at me 'cause I was drinking a Diet Coke

01:10:19.140 | during the first interview I did with him.

01:10:21.500 | I will drink Diet Coke.

01:10:23.340 | I've read the scientific literature

01:10:25.000 | and again, it's this 5% thing

01:10:26.800 | that I think is blown out of proportion.

01:10:29.300 | If I was to put a number on it,

01:10:31.180 | I would say if eating a high sugary meal

01:10:36.180 | or drinking a sugar-filled soda,

01:10:39.980 | what is that, 30 grams of sugar,

01:10:42.260 | let's say that's a 10 out of 10 bad for you.

01:10:45.940 | A Diet Coke might be a one.

01:10:47.880 | And if I'm, you know, which am I gonna do?

01:10:50.940 | I could have a 10 or a one or go without in my life.

01:10:54.140 | I'll do the one on occasion.

01:10:56.160 | I try to avoid them

01:10:58.220 | because I don't like the ones as much.

01:11:00.760 | But you can't say that sucralose

01:11:02.360 | is equivalent to drinking a sugary soda.

01:11:05.280 | There's just no comparison.

01:11:07.360 | And I think, what is it, stevia.

01:11:09.640 | I do use stevia whenever I can

01:11:11.280 | because it's a naturally sourced product

01:11:15.060 | and I haven't seen any good evidence yet

01:11:16.920 | that it's bad for you.

01:11:18.680 | But I think a lot of this is overblown

01:11:20.940 | and a lot of it's the media trying to give equal weight

01:11:24.300 | to stories.

01:11:25.340 | As you know, as a scientist,

01:11:27.180 | it can be frustrating when something's a 10

01:11:29.680 | and something's a one and they're equated.

01:11:31.980 | - How do I say this respectfully?

01:11:34.580 | I think if science journalists were required

01:11:37.660 | to post their credentials alongside their name,

01:11:42.500 | people would take the articles

01:11:44.500 | with an additional grain of salt, right?

01:11:46.740 | I mean, in other words,

01:11:47.580 | I think that the science media is mainly generated

01:11:50.940 | around two specific goals.

01:11:52.360 | One is to make people very, very afraid

01:11:55.260 | or get people very, very excited.

01:11:56.860 | And oftentimes the get people excited part

01:11:59.240 | is sponsored content.

01:12:00.400 | And I think that's overlooked.

01:12:01.860 | In any case, thank you for that.

01:12:04.160 | I want to talk about iron and iron load.

01:12:07.620 | We were talking earlier about ferritin

01:12:09.900 | and of course women, men straight.

01:12:13.280 | And so their iron needs are greater

01:12:16.460 | than people, men that don't menstruate

01:12:19.060 | or women that don't menstruate.

01:12:20.660 | I don't think we can get right down

01:12:22.980 | into how much iron somebody needs

01:12:24.860 | because it will vary person to person.

01:12:26.420 | But I was surprised to learn that iron

01:12:29.620 | is actually going to accelerate the aging process

01:12:33.660 | in various contexts.

01:12:35.160 | - Well, this is a new finding out of Spain.

01:12:39.860 | Manuel Serrano's lab has found that excess iron

01:12:43.980 | will increase the number of senescent cells in the body.

01:12:47.780 | And senescent cells are these zombie cells

01:12:49.840 | that accumulate as you get older and they sit there

01:12:52.260 | and they cause inflammation mainly

01:12:54.380 | and also can cause cancer.

01:12:56.500 | And it's found that if you get rid of these cells

01:12:58.620 | or never accumulate them, you stay younger.

01:13:02.100 | In animals and there's some really interesting studies

01:13:05.380 | out of Mayo Clinic in humans as well.

01:13:07.220 | So iron is a pro-senescent metal.

01:13:13.660 | And so what I think is that if you're taking excess iron

01:13:17.100 | as a supplement, you're probably accelerating

01:13:19.580 | your aging process.

01:13:21.060 | The other thing that I found really interesting

01:13:22.820 | is I've looked at hundreds of thousands

01:13:24.420 | of people's metabolism and their blood biomarkers.

01:13:29.220 | I was one of the first people inside Tracker

01:13:32.240 | as a board member and I'm still a scientific lead guy.

01:13:37.240 | So I can look anonymously at hundreds of thousands

01:13:39.860 | of people's blood work.

01:13:41.320 | And we also know how fit they are, how old they are.

01:13:44.420 | Some of them are marathon runners,

01:13:47.000 | some of them are CrossFit.

01:13:49.820 | And there's a signature of health

01:13:52.040 | that actually is different than your average person.

01:13:54.940 | Now, I'm not gonna say bad things about MDs

01:13:58.040 | 'cause a lot of my best friends are MDs

01:14:00.340 | and I work with them at Harvard Medical School.

01:14:03.340 | The issue though is that with MD training,

01:14:06.840 | it's there's a scale of what's normal.

01:14:09.900 | And if you're out of that normal range,

01:14:11.980 | something must be wrong.

01:14:12.980 | That's the paradigm that they work under.

01:14:15.240 | But first of all, everybody's different

01:14:17.280 | and you wanna know their baseline and track people

01:14:18.920 | over years to know what's normal for them.

01:14:21.700 | And what I find, for example,

01:14:23.060 | is people who are really healthy and live the way I do

01:14:26.600 | and have a diet that's fairly vegetarian, but not strict,

01:14:31.600 | still have slightly low hemoglobin levels,

01:14:35.220 | slightly low iron, slightly low ferritin,

01:14:38.080 | but we have super amounts of energy.

01:14:39.600 | We're not anemic and we're getting along with great in life.

01:14:43.700 | But a doctor who just looks at that might say,

01:14:46.260 | oh, we need to give you more iron, right?

01:14:48.580 | So what I'm getting at is an example

01:14:50.420 | of we need to personalize medicine

01:14:53.340 | and look at people over the long run

01:14:55.580 | to know what works for them and what's healthy for them,

01:15:00.120 | and not just work towards the average human,

01:15:02.040 | but work towards what's optimal for human.

01:15:04.700 | - I love that answer.

01:15:06.340 | You mentioned tracking and tracking over time,

01:15:08.460 | and this is a really interesting area

01:15:10.840 | that I know you have been focused on for a long time.

01:15:13.960 | I've been getting blood work done about every six months,

01:15:17.060 | frankly, since I was in college, I just got, I like data,

01:15:19.880 | and I got interested in supplementation and exercise

01:15:22.980 | 'cause it made me feel better,

01:15:24.260 | but I also wanna know what was going on under the hood.

01:15:27.020 | So you get numbers back.

01:15:28.780 | You get this hormone, that hormone,

01:15:30.340 | this blood glucose measure, et cetera.

01:15:33.820 | How do you make sense of the data?

01:15:35.820 | I mean, what Inside Tracker is doing aside,

01:15:38.260 | how do you personally make sense of the data

01:15:40.320 | in ways that might differ from the way

01:15:42.660 | that a standard MD might look at one of these charts?

01:15:45.140 | Because the standard practice is to say,

01:15:46.900 | is it red, yellow, or green, right?

01:15:49.320 | Is it basically too high or too low?

01:15:52.220 | Is it somewhere close to the margins or are you okay?

01:15:56.200 | Are you in these ranges?

01:15:57.900 | Are there any things that you pay attention to

01:16:00.280 | that you think are particularly interesting

01:16:02.820 | for people to just take note of?

01:16:04.280 | I mean, we're not asking you

01:16:05.220 | to go against anybody's physician.

01:16:06.920 | - Cool.

01:16:07.760 | - But what sorts of things should people

01:16:11.620 | start to educate themselves about

01:16:13.080 | in terms of what these molecules are on their charts

01:16:15.520 | if they choose to get them and what do you look at?

01:16:17.720 | - Yeah.

01:16:19.000 | Well, there's a lot there.

01:16:20.660 | The first is that you should be tracking things

01:16:23.840 | because one measurement isn't enough.

01:16:25.400 | These things vary and over time.

01:16:27.000 | And if you can have a decade or more of data,

01:16:29.440 | it's super informative as you know well know,

01:16:33.760 | as you know.

01:16:36.020 | So the physician, interestingly, my physician,

01:16:38.940 | let's take him as an example.

01:16:40.420 | So he sees me, he says, how are you feeling?

01:16:46.020 | I'm feeling great.

01:16:47.160 | Okay, see you next year.

01:16:48.300 | That's craziness.

01:16:49.260 | Anyway, so I say, okay, stop.

01:16:51.000 | Let's talk a little bit about-

01:16:52.840 | - Let me educate you.

01:16:53.880 | That's what David tells his physician.

01:16:55.680 | I imagine that the like 12-year-old David Sinclair

01:16:58.180 | says to his physician, listen,

01:16:59.680 | let's have a different discussion.

01:17:01.080 | Is that how it works?

01:17:01.920 | - It is.

01:17:02.740 | - Okay, he finds me pretty annoying as does my dentist.

01:17:06.120 | But so I said, stop, hang on.

01:17:08.040 | I've got this data.

01:17:09.760 | I've got the inside tracker data.

01:17:11.100 | So I pull that up on the screen

01:17:13.060 | and I'm showing him the changes in my cholesterol,

01:17:16.960 | in my CRP, which is inflammatory marker, as you know.

01:17:20.960 | And we're going through it

01:17:21.800 | and you can see things change over time

01:17:23.360 | and I've corrected them as they go slightly out

01:17:25.840 | of the optimal range for me,

01:17:27.760 | which is different than what he would do, of course.

01:17:30.000 | But what was funny is that he says, this is great.

01:17:33.140 | I love this data, but I'm not allowed to get this

01:17:36.280 | because of course the insurance companies won't pay for it.

01:17:39.900 | So again, you can pay out of pocket.

01:17:41.900 | It's not super expensive.

01:17:43.140 | I would say if you save a bit of money on a coffee,

01:17:48.140 | you can afford this kind of stuff.

01:17:50.300 | But the main point is that doctors do like this data.

01:17:53.580 | It's just that they're unable to spend the money

01:17:55.840 | on every one of their patients to get it.

01:17:58.060 | - Is there a code word that someone can use

01:18:00.340 | with their physician that will trigger

01:18:01.940 | a comprehensive blood test?

01:18:03.520 | I keep trying to figure out what's the code

01:18:06.000 | that one needs to ask or tell their doctor,

01:18:08.420 | like I'm feeling blank so that they get a full blood panel.

01:18:12.060 | Well, do you have to be hemorrhaging

01:18:13.660 | from the gut or something?

01:18:16.060 | - Well, I usually use the WTH method,

01:18:18.620 | which is what the hell?

01:18:19.880 | And then he says, okay, we'll do it.

01:18:22.400 | - 'Cause I think a lot of people out there are thinking,

01:18:24.100 | look, I'd love to have blood work repeatedly over time,

01:18:26.780 | but that's hard to get for financial reasons,

01:18:29.360 | but also a lot of people just don't know

01:18:30.540 | how to approach the conversation.

01:18:32.660 | And this is one of the things

01:18:33.500 | that I hope that we can educate people on,

01:18:36.000 | that they deserve to know what's going on inside their body

01:18:39.380 | and that it makes a doctor's visit worthwhile

01:18:42.440 | and that you don't have to feign illness in order to do it.

01:18:46.060 | - Right, yeah, and a lot of people do.

01:18:47.860 | So I would say if you can afford these tests,

01:18:49.940 | there are an increasing number of companies

01:18:52.020 | that offer these tests.

01:18:53.980 | Insight Tracker is one of them.

01:18:55.900 | And you just do it a couple of times a year at a minimum,

01:18:59.700 | and then you can share that with your doctor.

01:19:01.800 | If you can't afford that, then I would say to your doctor,

01:19:05.060 | here are the main ones that Andrew and David do.

01:19:09.440 | - Yeah, they must.

01:19:10.420 | - And there's an email that is something like,

01:19:13.220 | or a phone number rather, it's 555-5555.

01:19:16.620 | I think if they have any complaints,

01:19:17.900 | they can just call that number.

01:19:19.940 | David will pick up on East Coast business hours,

01:19:22.840 | and I'll pick up outside of those hours.

01:19:24.940 | But there were some main ones, I would say.

01:19:26.840 | Your blood sugar levels, you want to do your HbA1c,

01:19:29.260 | which is your average glucose levels over the month.

01:19:32.260 | There's CRP, which I mentioned for inflammation.

01:19:35.100 | - Let's talk about C-reactive protein for a second,

01:19:37.020 | 'cause I think it's been shown to be an early marker

01:19:40.740 | of macular degeneration, of heart disease,

01:19:43.500 | of a variety of different things.

01:19:45.360 | CRP is something that we don't hear enough about, I think.

01:19:48.940 | Maybe, what do you know about CRP that I don't?

01:19:51.680 | I'm guessing a lot, but wow.

01:19:53.340 | - Well, it was originally picked up as something

01:19:55.460 | that was associated with heart disease

01:19:57.020 | in the Framingham study, I believe.

01:19:59.420 | It is the best marker for cardiovascular inflammation,

01:20:03.540 | and also we use it as a predictor of longevity.

01:20:07.260 | And its levels go up with mortality.

01:20:12.180 | And so this is an association, but there's enough data

01:20:14.660 | that I would say if you have high levels of CRP,

01:20:17.600 | you need to get your levels down quickly.

01:20:20.420 | And the levels usually go up with age.

01:20:23.140 | And with levels of inflammation.

01:20:24.580 | So the ways to get it down would be to switch the diet,

01:20:28.040 | eat less, try to eat more vegetables,

01:20:30.280 | you'll find it will come down.

01:20:31.580 | There are also drugs that can do it.

01:20:33.720 | Anti-inflammatories can do it as well.

01:20:37.260 | But CRP is, it's actually HCRP.

01:20:40.020 | There's a high-sensitive or HSCRP.

01:20:41.900 | Your doctor will know.

01:20:43.300 | Get one of those readings,

01:20:44.260 | 'cause if you've got normal blood sugar levels,

01:20:47.220 | your doctor, or fasting blood sugar levels,

01:20:50.300 | your doctor might say you're fine.

01:20:52.020 | But a lot of people have normal blood sugar,

01:20:54.020 | but have high CRP, which is just as bad for you long-term,

01:20:58.500 | and can predict a future heart attack.

01:21:01.080 | - On the lines of heart attack,

01:21:02.360 | I want your thoughts on cholesterol,

01:21:05.100 | and serum cholesterol, and dietary cholesterol.

01:21:07.660 | I cannot for the life of me

01:21:09.920 | get my arms around this literature.

01:21:12.080 | And even if I ignore all the essentially nonsense

01:21:16.080 | that's out there in various social media groups

01:21:19.240 | saying cholesterol is the worst thing in the world,

01:21:22.700 | or cholesterol is not, or dietary cholesterol

01:21:26.060 | has nothing to do with serum cholesterol

01:21:28.540 | and nothing to do with longevity,

01:21:29.800 | I can't seem to sort through the very basic data

01:21:34.800 | that essentially ask,

01:21:37.340 | is having high levels of LDL going to kill me earlier?

01:21:43.060 | Should I be striving to always reduce LDL and increase HDL?

01:21:47.180 | Is that a reasonable goal?

01:21:48.640 | And if so, is dietary cholesterol

01:21:52.020 | the primary determinant of that?

01:21:53.500 | And just as a final point about this,

01:21:56.640 | I am aware of quite good data that shows that anorexics,

01:21:59.780 | people that essentially eat no food unless you force them to,

01:22:02.860 | can often have very high LDL.

01:22:06.900 | So their dietary cholesterol is essentially zero,

01:22:10.340 | and so they're manufacturing a lot of their own.

01:22:12.260 | So realize this isn't your primary area of expertise,

01:22:15.860 | but you're a smart guy.

01:22:17.420 | You think about this kind of stuff a lot.

01:22:19.720 | What do you think is going on with the cholesterol literature

01:22:22.100 | and will we ever get to the bottom of this

01:22:24.620 | as a scientific and medical community?

01:22:26.420 | Because to me, it is rather perplexing.

01:22:29.180 | - It is, but you can get through the politics.

01:22:34.600 | I know a fair bit about cholesterol

01:22:35.940 | 'cause it's in my family history,

01:22:39.060 | and I was headed for an early death.

01:22:41.580 | My grandmother had a stroke at 30.

01:22:43.400 | That's how bad I am in terms of my genetics.

01:22:46.820 | So I went on a statin,

01:22:48.020 | and I know there's a lot of people

01:22:49.260 | who say that statins long-term are bad.

01:22:51.380 | It might, it's associated with Alzheimer's disease.

01:22:54.300 | I've been taking a statin since I was 29,

01:23:00.420 | and that's 'cause I forced my same doctor

01:23:02.740 | to give me the statin.

01:23:04.320 | The conversation was something like this.

01:23:06.100 | You're too young to be on a statin.

01:23:08.340 | I said, what, you want me to have a heart attack

01:23:10.180 | before you give me something?

01:23:11.400 | Give it to me now.

01:23:12.240 | So 29, I've been on a statin,

01:23:13.940 | and my cholesterol was way up beyond 300,

01:23:16.780 | which is a massive, massive,

01:23:18.100 | basically my blood was creamy to look at.

01:23:20.580 | So I've now got my cholesterol down to low, low levels

01:23:24.620 | to what would it be?

01:23:25.980 | You could check on my inside tracker,

01:23:28.140 | but so my ratio of HDL to LDL,

01:23:30.500 | which you want to be less than five, is now two,

01:23:33.100 | and the LDL is below 100, so it's all good.

01:23:36.300 | And I've measured my cardiovascular health with an MRI.

01:23:39.300 | I've got a movie of my heart beating.

01:23:41.340 | I've still got a heart of a 20-year-old.

01:23:43.400 | So that's working.

01:23:45.380 | I'm willing to forego the risk

01:23:46.780 | that the statin is causing problems later

01:23:48.660 | because of my family history, but other people,

01:23:51.740 | I would say be aware that statins aren't perfect drugs.

01:23:56.740 | There are some interesting new ones.

01:23:58.380 | There's one called the PSK-9 inhibitor,

01:24:00.780 | which is I think fortnightly, every two weeks, injection.

01:24:04.360 | That blocks the release of LDL from the liver.

01:24:08.040 | And then that seems to be great for lowering cholesterol,

01:24:13.220 | but also has other benefits that might be pro-longevity.

01:24:17.340 | And there were some people that I was just talking to

01:24:20.340 | are on the cutting edge of this,

01:24:21.860 | and their doctors are trying them on this drug

01:24:23.900 | instead of the statin.

01:24:25.760 | So you could talk to your doctor about that.

01:24:28.260 | - Do you avoid dietary cholesterol for that reason also?

01:24:32.740 | Red meat, butter.

01:24:34.040 | I mean, I happen to love butter.

01:24:35.300 | I love red meat.

01:24:36.980 | I realize there's some people who don't.

01:24:39.720 | My cholesterol is a little bit high,

01:24:40.920 | but I'm working to bring that down a bit,

01:24:43.460 | although not by altering my food intake yet.

01:24:46.660 | But what do you think is the relationship

01:24:49.340 | between dietary cholesterol and serum cholesterol?

01:24:51.740 | And what's going on with the liver?

01:24:53.480 | Why are anorexics, why is their serum cholesterol so high

01:24:57.500 | when they're eating nothing?

01:24:58.440 | - Yeah, well, there've been a number of papers

01:25:00.160 | over the years that have been ignored.

01:25:02.040 | And our friend Peter Atiyah brought to my attention recently

01:25:06.260 | a new study that I think definitively said

01:25:09.140 | that dietary cholesterol has almost zero impact

01:25:12.460 | on blood cholesterol levels.

01:25:13.800 | - Good.

01:25:14.640 | - Yeah, so I'm annoyed,

01:25:17.200 | 'cause I've been avoiding eggs and butter

01:25:19.240 | for most of my life, and I didn't have to.

01:25:22.140 | - So I have eggs plenty of time, or at least in your case.

01:25:26.260 | - Yeah, yeah, so that's the thing.

01:25:28.640 | You can eat these foods that were once banned,

01:25:31.680 | because it's very difficult to take cholesterol up

01:25:34.620 | into the body from the gut,

01:25:36.140 | and most of it's being synthesized in the body.

01:25:39.280 | - Wow, I'm just pausing there for a second,

01:25:41.160 | because I think that it's what we've been told,

01:25:45.920 | six meals a day, eat a lot of grains and fruits

01:25:49.840 | and this kind of thing, avoid cholesterol.

01:25:54.840 | I mean, basically everything we learned in the '80s and '90s

01:25:58.880 | and early 2000s is getting flipped on its head now.

01:26:01.940 | But, and I think this is a very strong caveat

01:26:07.840 | that's important to mention.

01:26:09.380 | Amino acids, in particular the amino acids

01:26:14.000 | that come from animal products, right?

01:26:17.200 | Seem to have some pro-aging effect on them, right?

01:26:21.240 | At least the way that I've heard you describe your diet.

01:26:24.720 | And I'm somebody who enjoys meat, I like it.

01:26:27.840 | But, so I'm by no means a vegan at all.

01:26:31.160 | But I've heard you say you eat mostly plants,

01:26:36.000 | but a little bit of fish or chicken

01:26:38.160 | or something of that sort, or eggs or...

01:26:40.640 | But is that specifically to avoid

01:26:43.520 | excessive amino acid intake?

01:26:45.160 | Or is it something specific about plants

01:26:46.960 | that excites you with respect to...

01:26:50.080 | I mean, vegetables are delicious too.

01:26:52.100 | But what is it?

01:26:52.940 | Is it something great about plants?

01:26:54.060 | Or is it something bad about...

01:26:55.500 | When I think of meat,

01:26:56.440 | I guess the biologist in me thinks amino acids, right?

01:26:59.400 | I don't think top sirloin, I think amino acid.

01:27:01.760 | No, I think top sirloin as I'm eating it,

01:27:03.300 | but really what they are are amino acids,

01:27:05.760 | including leucine.

01:27:07.220 | - Yeah.

01:27:08.400 | Well, there are two good things about plants

01:27:10.680 | and neither of them is taste for me.

01:27:13.800 | I would eat steak all the time if I could.

01:27:15.680 | I did when I was a kid, I'm an Australian.

01:27:18.480 | But plants have two benefits.

01:27:19.740 | One is that they're highly nutritious

01:27:22.800 | and they'll give you a lot of the vitamins

01:27:26.520 | and nutrients that I need.

01:27:28.060 | I don't take a multivitamin.

01:27:29.300 | I don't want to have the excess iron in my body.

01:27:32.200 | So there's that high density nutrition.

01:27:34.160 | So those dark leaves, if it's a spinach salad, great.

01:27:37.660 | Second is that there is what's called

01:27:41.360 | xenohormatic molecules in plants.

01:27:44.360 | That term xenohormesis is a term

01:27:46.960 | that I came up with my friend Conrad Howitz,

01:27:51.160 | which means stressed plants make molecules

01:27:54.680 | that benefit your health.

01:27:56.220 | I'll break it down.

01:27:57.120 | Xeno means between species and hormesis

01:27:59.820 | is the term whatever doesn't kill you

01:28:01.160 | makes you stronger and live longer.

01:28:03.900 | And the idea is that when plants are stressed out,

01:28:07.600 | think of a grapevine that's dried out

01:28:09.600 | and they're starting to harvest the grapes,

01:28:11.180 | which is typically how it's done.

01:28:13.160 | They are full with resveratrol

01:28:14.520 | because resveratrol is a plant defense molecule

01:28:17.920 | that I think is made to activate

01:28:19.800 | those sirtuin genes in a plant.

01:28:21.480 | So plants have sirtuins just like we do.

01:28:24.200 | But by purifying or at least concentrating

01:28:27.000 | in a light proof bottle and keeping it out of the air,

01:28:30.920 | we stabilize the xenohormatic molecule

01:28:33.600 | or it's a cocktail, not just one, there's others in wine.

01:28:36.900 | We then ingest those and get the benefits

01:28:39.680 | of activating our own defenses

01:28:41.200 | because our food was getting stressed out.

01:28:43.540 | And by stressed, I don't mean psychologically stressed,

01:28:45.580 | I mean biologically stressed.

01:28:47.460 | And so I try to eat plants

01:28:49.520 | that have gone through a bit of stress.

01:28:51.800 | They might be brightly colored,

01:28:53.120 | they've had too much sun or got nibbled on by a caterpillar.

01:28:56.160 | So you go to places where it's organic or it's fresh, local,

01:29:00.360 | and those are the plants that aren't perfect

01:29:01.860 | and they probably have high concentrations

01:29:03.200 | of these molecules.

01:29:04.040 | And in addition, I also buy the supplements

01:29:06.640 | to make sure I'm getting enough of those as well.

01:29:08.640 | - Which supplements mimic that?

01:29:09.920 | - Well, so resveratrol will,

01:29:11.080 | there's another one called chrysitin or chrysitin,

01:29:13.480 | some people call it,

01:29:14.600 | which you find in trace amounts in apples and onions.

01:29:18.480 | And we also showed back in 2003

01:29:20.720 | that it activates sirtuins as well.

01:29:23.240 | But others have 20 years later found

01:29:25.720 | that it kills senescent cells

01:29:28.520 | or helps kill senescent cells.

01:29:30.680 | So it's a double whammy with that molecule.

01:29:33.520 | - And are you actively picking out the peaches

01:29:35.560 | that look like they were nibbled on by a caterpillar?

01:29:38.700 | - No, but I don't worry if they've been banged up a bit.

01:29:43.320 | - What's the story with antioxidants?

01:29:45.260 | Are they of any value whatsoever?

01:29:46.940 | Because the way that you described them at the beginning

01:29:50.300 | and what I've heard recently

01:29:51.880 | is that they are not all the rage for anti-aging.

01:29:56.160 | What are they doing that's useful?

01:29:58.820 | Should we be seeking out antioxidants anyway

01:30:02.200 | for other cellular health purposes?

01:30:04.600 | - Well, yeah, antioxidants are not going to hurt you

01:30:06.700 | unless you take mega doses.

01:30:08.360 | We do need some oxidants for our immune system.

01:30:12.100 | And there's even what's called mitohormesis,

01:30:14.200 | which is your mitochondria power packs

01:30:16.240 | need to have a little bit of these free radicals

01:30:18.540 | to be able to function.

01:30:19.860 | So you don't want to overdose on these antioxidants,

01:30:23.520 | vitamin C, vitamin E, don't overdo it.

01:30:26.800 | - You don't take a multivitamin, correct?

01:30:28.520 | - Right.

01:30:29.800 | - I think I'm going to stop after this conversation

01:30:31.860 | 'cause I've always just taken one

01:30:33.100 | for the kind of insurance purpose,

01:30:34.640 | which is a stupid purpose, not actual insurance,

01:30:38.480 | but just thinking, oh, you know,

01:30:40.520 | I'll top off on my ACBD.

01:30:42.880 | - Right, and I'll pee out what I don't need.

01:30:45.160 | - Right, but that never bothered me.

01:30:46.640 | The whole expensive pee thing never got,

01:30:48.440 | that argument never got me

01:30:50.620 | because a good vitamin is not that expensive.

01:30:53.760 | I just figured better safe than sorry,

01:30:56.400 | but it may be that it's detrimental.

01:30:58.840 | - Well, it can in the case of iron,

01:31:00.760 | as we discussed in the antioxidants.

01:31:02.700 | So when I came into the aging field in the early 1990s,

01:31:07.640 | it was all about antioxidants.

01:31:09.120 | And we thought that enzymes by the name of catalase

01:31:12.540 | and superoxide dismutase

01:31:13.880 | were going to be the key to longevity.

01:31:16.500 | It turns out that it's largely been a failure

01:31:18.940 | that giving animals and humans antioxidants

01:31:23.800 | haven't had the longevity benefits that we dreamed of.

01:31:27.500 | And the main reason is that there's a lot more going on

01:31:31.440 | than just free radical damage.

01:31:33.080 | The epigenome gets disrupted.

01:31:35.720 | We've got these proteins misfolding.

01:31:37.480 | So the problem really has been that we didn't realize

01:31:42.080 | that you need to turn on the body's natural defenses

01:31:45.560 | against that plus a whole host of other things

01:31:47.880 | to get the true benefits.

01:31:50.120 | But I'm not going to say it's a problem

01:31:51.360 | taking an antioxidant drink.

01:31:53.920 | Pomegranate juice for one is full of good stuff,

01:31:56.000 | including xenohormatic molecules.

01:31:58.540 | But resveratrol is a good case in point,

01:32:00.880 | which is when I worked on resveratrol

01:32:03.360 | as a longevity molecule,

01:32:05.080 | first we showed it in yeast and worms and flies and mice.

01:32:07.920 | Before that, it was thought that resveratrol

01:32:11.640 | was good for your heart in red wine

01:32:13.760 | when you drink red wine because it's an antioxidant.

01:32:16.740 | So then we showed that it extended the lifespan

01:32:18.880 | of yeast cells through this genetic pathway, the sirtuins.

01:32:23.880 | And we then tested whether resveratrol,

01:32:28.440 | if we changed one atom to make it not an antioxidant,

01:32:31.880 | guess what, it still worked fine.

01:32:33.640 | So it wasn't its antioxidant activity

01:32:35.500 | that was extending lifespan.

01:32:36.560 | It was its ability to turn on the yeast's defenses

01:32:38.980 | against aging.

01:32:40.140 | Conversely, when we gave the yeast antioxidants,

01:32:42.760 | they looked shorter.

01:32:44.520 | So yeah, that was the beginning of my transformation

01:32:46.880 | into thinking, turn on the body's defenses,

01:32:49.040 | don't give it the antioxidants.

01:32:50.800 | - This is an opportunity for me to say

01:32:53.200 | something that I've been wanting to say for a long time,

01:32:55.660 | which is that what's so wonderful about science

01:32:58.640 | is that because the goal is mechanism,

01:33:01.520 | you can really start to understand, as you just described,

01:33:04.320 | what actually mediates a process is very different

01:33:08.440 | than what modulates a process.

01:33:10.020 | I mean, if a fire alarm goes off in the building right now,

01:33:12.160 | it's going to modulate our attention.

01:33:13.980 | That doesn't mean that it controls our attention.

01:33:16.440 | It's not mechanistically relevant.

01:33:18.320 | And so I think this thing about antioxidants

01:33:20.160 | is one of these cases, it sounds like,

01:33:22.440 | where it's in the right ballpark,

01:33:24.840 | but until one really unveils the mechanism as you have,

01:33:27.720 | you can be, one can or a field can be badly wrong

01:33:32.720 | for a very long period of time.

01:33:34.480 | It sounds like the sirtuins and really getting down

01:33:38.040 | to the guts of the machinery of what causes cells to age

01:33:41.400 | is really what it's about.

01:33:43.400 | Zooming way out, what are the behavioral tools

01:33:48.000 | that one can start to think about

01:33:49.720 | in terms of ways to modulate these,

01:33:52.420 | basically the way that DNA is being expressed

01:33:55.120 | and functioning?

01:33:56.460 | I've heard you talk before about hormesis of other sorts,

01:34:00.680 | cold exposure.

01:34:01.960 | We talked about fasting.

01:34:03.460 | We talked about exercise in broad terms,

01:34:05.560 | but what about any evidence, if it exists,

01:34:10.760 | as to whether or not aerobic training versus weight training,

01:34:14.320 | these sorts of things?

01:34:16.060 | In other words, what are the sorts of things

01:34:17.600 | that people can do to improve the sirtuin pathway?

01:34:21.320 | And I realize that they're caveats.

01:34:23.260 | We can't go directly from a behavior to sirtuins,

01:34:25.440 | but in the general theme, what can people do?

01:34:28.400 | What do you do?

01:34:29.340 | - Right.

01:34:30.180 | Well, we know that aerobic exercise in mice and rats

01:34:33.640 | raises their NAD levels and their levels of,

01:34:37.000 | one of the genes goes up to actually number one

01:34:39.880 | and number three.

01:34:41.200 | What we don't know yet is what type of exercise

01:34:44.960 | is optimal to get them to change.

01:34:47.600 | We will learn, we're doing work.

01:34:49.220 | Now it's revealed that we're doing work

01:34:50.840 | with the military in the US

01:34:52.580 | to try and understand that kind of thing.

01:34:55.040 | And I'll always tell you and the public,

01:34:57.200 | when I don't know something, I'm not gonna extrapolate.

01:35:00.380 | But what do I do?

01:35:02.120 | I base my exercise on the scientific literature,

01:35:05.120 | which has shown that maintaining muscle mass

01:35:08.800 | is very important for a number of reasons.

01:35:10.880 | The two main ones are,

01:35:12.760 | you wanna maintain your hormone levels.

01:35:14.280 | I'm an older male losing my testosterone

01:35:17.080 | and muscle mass over time.

01:35:18.900 | And by exercising, I will maintain that and have.

01:35:23.220 | In fact, I probably haven't had a body like this

01:35:26.080 | since I was 20.

01:35:26.920 | So that's one of the benefits of having this lifestyle.

01:35:30.320 | - Sorry to interrupt you.

01:35:31.160 | You know, we did an episode on hormones

01:35:33.560 | and there are data in humans that show

01:35:35.500 | that there are some males in their 80s and 90s

01:35:39.940 | where their testosterone is equivalent

01:35:41.860 | to the average of 25 and 30 year olds.

01:35:44.580 | I can get you that information.

01:35:45.860 | It is really impressive studies.

01:35:48.300 | Unfortunately, they didn't include a lot of information

01:35:51.180 | about the lifestyle factors, et cetera.

01:35:52.820 | But this idea that testosterone goes down with age,

01:35:55.660 | it might be the trend,

01:35:59.660 | but it's not necessarily a prerequisite.

01:36:03.860 | - Right, I believe in naturally increasing

01:36:06.580 | and maintaining these hormone levels.

01:36:08.060 | And I've been measuring them for a long time.

01:36:10.700 | And I could see for me,

01:36:11.780 | my testosterone levels were steadily,

01:36:14.100 | levels were going down.

01:36:15.140 | - And then you got tenure and they went back up again.

01:36:18.100 | - No, I actually became complacent and it was the worst.

01:36:23.100 | Actually, my age changed in the wrong direction after that

01:36:26.660 | 'cause I was relaxed and not worried about the future.

01:36:30.120 | But then I got serious and I actually,

01:36:33.140 | according to the inside track algorithm,

01:36:35.180 | got my age down from 58 to 31 in a matter of months.

01:36:40.180 | That was a big drop.

01:36:41.820 | And I've been getting steadily younger

01:36:43.420 | over the last 10 years,

01:36:44.660 | according to that measurement, the blood tests.

01:36:46.500 | - What about estrogen?

01:36:47.420 | Because women are different in the sense that they do,

01:36:50.760 | the number of eggs and the ovaries change over time, right?

01:36:56.020 | Do you think that they can maintain estrogen levels

01:36:58.900 | over longer periods of time

01:37:01.620 | using some of these same protocols?

01:37:03.300 | - Well, yeah, I get into trouble from a certain university

01:37:06.600 | when I talk about this too much.

01:37:08.920 | - About estrogen?

01:37:10.220 | - Just about fertility and long story.

01:37:14.540 | I don't want to get too much into the anecdotes,

01:37:18.740 | but I'll tell you the science,

01:37:19.740 | which is that if you take a mouse

01:37:24.520 | and put it on fasting or caloric restriction

01:37:27.700 | for up until the point where it should be infertile,

01:37:31.780 | so that's about it at a year of age,

01:37:33.460 | a mouse gets infertile, a female mouse.

01:37:35.180 | - Due to fasting or simply to aging?

01:37:38.140 | - Due to aging, due to aging.

01:37:39.920 | The fasting, it's not an extreme fast,

01:37:42.800 | it's just less calories.

01:37:44.720 | Then you put them back on a regular food

01:37:47.320 | and they become fertile again

01:37:49.220 | for many, many months afterwards.

01:37:51.500 | So the effect on slowing down aging

01:37:55.100 | is also on the reproductive system.

01:37:57.020 | - Interesting.

01:37:58.060 | - And so I wouldn't say to any woman,

01:38:00.240 | I wouldn't think that they should become super skinny

01:38:02.660 | to try and preserve fertility.

01:38:04.160 | That's not what I'm saying.

01:38:05.500 | But these pathways that we work on,

01:38:07.220 | these sirtuins are known to delay infertility

01:38:10.420 | in female animals.

01:38:12.140 | Case in point, I'm one of the lead authors on a paper

01:38:15.140 | where we used NMN.

01:38:16.660 | Remember, this is the gas, the fuel,

01:38:18.740 | the petrol for the sirtuins.

01:38:20.420 | We gave old mice, one group of mice was 16 months old.

01:38:27.260 | Remember, they came in fertile at 12.

01:38:30.300 | Gave them NMN, and I think it was only six weeks later,

01:38:34.820 | they had offspring.

01:38:37.420 | They became fertile again,

01:38:38.740 | which goes against biology, a textbook biology,

01:38:42.020 | which is that female mammals run out of eggs.

01:38:45.380 | Turns out that's not true.

01:38:47.420 | You can rejuvenate the female reproductive system

01:38:50.500 | and even get them to come out of mouseopause,

01:38:53.300 | as we call it.

01:38:54.660 | So that's a whole new paradigm in biology as well.

01:38:57.540 | - That's super interesting.

01:38:58.780 | Sorry to interrupt you,

01:38:59.620 | but I'm reminded of a set of studies

01:39:02.300 | that were done by your former colleagues,

01:39:04.540 | 'cause they're no longer there,

01:39:05.380 | David Hubel and Torrance and Wiesel,

01:39:06.820 | my scientific great-grandparents,

01:39:08.200 | won the Nobel Prize for discovering

01:39:10.160 | what are called critical periods,

01:39:11.980 | this phase of early development

01:39:13.380 | when the brain is extremely plastic.

01:39:16.080 | And a big part of their work was to show

01:39:18.300 | that after a certain point, the critical period shuts down.

01:39:20.880 | Essentially, the brain can't change,

01:39:22.420 | or not nearly as much.

01:39:24.700 | And then people came along later

01:39:25.860 | and showed that you could open up

01:39:27.100 | these critical periods again, but very briefly,

01:39:29.580 | and it takes a very specific stimulus, essentially,

01:39:34.180 | high degrees of focus, et cetera.

01:39:36.400 | However, there's a well-known phenomenon in this literature

01:39:40.340 | where if you take an animal, and to some degree,

01:39:44.380 | this has been shown in humans as well,

01:39:46.900 | and you let them pass through the critical period,

01:39:49.860 | but then you essentially sensory deprive them.

01:39:52.760 | You take away experience, you close both eyes.

01:39:56.220 | You essentially reopen the critical period.

01:39:58.980 | So it seems like, and I couldn't help but mention this,

01:40:01.220 | that there's this parallel between what we're talking about

01:40:03.560 | here with fertility and neuroplasticity where,

01:40:05.980 | yes, there's a timer where certain things are available

01:40:09.180 | to the organism early in life,

01:40:10.980 | and then they tend to taper off.

01:40:12.520 | It's not an open and shut, but they taper off.

01:40:14.680 | But then a deprivation can actually reactivate

01:40:18.140 | the availability of that process.

01:40:21.220 | Forgive me, I just couldn't help but mention it,

01:40:22.820 | but to me, both of those things are associated with youth,

01:40:26.460 | fertility and neuroplasticity.

01:40:28.260 | And so I think that it'd be so interesting,

01:40:30.620 | I'd love to collaborate with you on this,

01:40:32.080 | to explore how neuroplasticity might actually be regulated

01:40:35.020 | by these things like the sirtuins.

01:40:37.480 | - Right, and the sirtuins do control memory

01:40:40.780 | in neurons as well.

01:40:41.940 | So what I think is really interesting

01:40:44.220 | is that what we're learning from work

01:40:46.760 | that you and your colleagues have done

01:40:48.180 | and in my life as well,

01:40:49.760 | is that the body has remarkable powers of healing

01:40:52.840 | and recovering from illness and injury.

01:40:56.820 | And what we once thought was a one-way street

01:40:58.880 | and you just can't repair,

01:41:01.120 | you can't get over these diseases, you can reset the system.

01:41:04.580 | And the body can really get rejuvenated in ways

01:41:06.920 | that in the future we'll wonder,

01:41:08.400 | why didn't we work on this earlier?

01:41:10.440 | The future of humanity is more like us

01:41:13.560 | walking around like Deadpool.

01:41:15.080 | We'll probably be cleaner and we won't smell as badly,

01:41:18.080 | but Deadpool, if you don't know,

01:41:21.080 | can get injured and just recover.

01:41:22.520 | It's very hard to injure this guy

01:41:24.800 | and we're gonna be the same.

01:41:26.720 | There are many species, you cut off the limb,

01:41:28.840 | the limb grows back.

01:41:29.680 | - Salamanders, yeah.

01:41:31.280 | - We are now learning how to tap into that system.

01:41:33.960 | And in part, what we're doing

01:41:35.360 | is reversing the age of those cells

01:41:38.160 | and telling them how to read the genes correctly again,

01:41:41.160 | reversing the age of that epigenome.

01:41:43.840 | And when you do that, the cells, the brain, for instance,

01:41:46.920 | the skin, we did the optic nerve.

01:41:50.120 | - Now let's talk about those results for a second.

01:41:51.800 | Then I want to make sure that we return

01:41:53.040 | to some of these behavioral protocols.

01:41:54.720 | You had this amazing paper at the end of last year,

01:41:56.800 | cover article, full article in Nature,

01:42:00.100 | showing that essentially a small menu

01:42:03.240 | of transcription factors,

01:42:05.440 | which control gene expression, et cetera,

01:42:07.820 | could essentially reverse the age of neurons in the eye

01:42:11.800 | and rescue those cells against damage,

01:42:14.940 | essentially allow blind mice to see again

01:42:18.760 | and offset degeneration of these retinal cells.

01:42:21.560 | Incredible paper and such a boon to the field.

01:42:26.560 | Where does that stand now in terms of human clinical trials?

01:42:30.100 | I mean, what are you envisioning

01:42:32.660 | in terms of the trajectory of those data

01:42:35.240 | from mice into humans someday?

01:42:38.640 | - Right. Well, to get to the point immediately,

01:42:43.480 | we're going to be testing the treatment on monkeys,

01:42:48.480 | just for safety reasons.

01:42:50.800 | And then the first patient should be done sometime in 2022,

01:42:55.160 | early 2023, and we're going to try to recover blindness.

01:42:58.560 | - This involves making an injection

01:43:00.320 | of a virus into the eye, right?

01:43:02.680 | Right now, there's no way that I am aware of

01:43:05.280 | to manipulate these transcription factors

01:43:06.980 | through a pill or some other.

01:43:08.720 | - That's what we're working on in my lab

01:43:10.480 | at Harvard right now.

01:43:11.760 | So it will be- - Pill-based modulation

01:43:13.480 | of transcription factors. - It will be a proper pill

01:43:15.000 | and the whole body gets rejuvenated by 20 years.

01:43:16.960 | That's what we're aiming for.

01:43:18.440 | Now we do it with gene therapy in the eye and other places.

01:43:23.100 | So in the eye, yes, it's single injection.

01:43:25.760 | The genes go into the retina and we can turn it on

01:43:29.160 | with a drug called doxycycline.

01:43:31.240 | And we do that in the mice for four to eight weeks.

01:43:34.680 | Then the eye gets younger.

01:43:36.160 | We can measure that 'cause we can measure the clock.

01:43:38.620 | And then the vision comes back in those mice.

01:43:41.780 | And I don't see any reason why it shouldn't work in people

01:43:44.860 | because it's the same structures and mechanisms

01:43:47.500 | that are on in the human as well.

01:43:49.860 | Now these- - And it's one injection.

01:43:51.520 | As you mentioned, injections into the eye,

01:43:53.580 | obviously nobody should do this

01:43:55.060 | outside of an ophthalmology clinic.

01:43:57.040 | And they're definitely by an ophthalmologist.

01:44:00.080 | But the injections into the eye are painless

01:44:03.660 | if done correctly by the right person.

01:44:05.460 | It sounds dreadful, but it's actually,

01:44:07.380 | I've seen it done hundreds of times.

01:44:09.260 | I've done it thousands of times and it's not to myself,

01:44:13.200 | but to other creatures.

01:44:14.720 | And there's a way of doing this

01:44:15.840 | that's completely painless to the person.

01:44:17.540 | - Oh, there are a few.

01:44:18.380 | It's a tiny, tiny needle too.

01:44:20.260 | But the great thing about this

01:44:21.300 | is that it's a one-time treatment.

01:44:22.820 | Those genes go into the back of the eye

01:44:24.260 | and stay there forever.

01:44:27.460 | And you can just turn them on whenever you want.

01:44:29.840 | So what we've found is you can turn them on in the mice,

01:44:32.380 | they get their vision back, and then you turn it off again.

01:44:35.420 | And so far, many months out, the benefit has remained.

01:44:39.540 | But if it does decline, we'll just turn it back on

01:44:42.220 | and reset the system, rinse and repeat.

01:44:45.140 | So one day, what's exciting

01:44:46.340 | is that we could potentially do this across the entire body

01:44:49.340 | and just take this antibiotic every five years

01:44:53.480 | and go back time and time again.

01:44:55.520 | - In thinking about the body

01:44:57.580 | and what's going on under the hood,

01:44:58.860 | I'm amazed still that there isn't a simple,

01:45:02.820 | affordable technology that would allow me

01:45:04.640 | to just look into my body

01:45:05.760 | and see whether or not there are any tumors growing anywhere.

01:45:08.260 | I mean, it's not that hard to look into the body.

01:45:10.780 | I mean, that the technology exists.

01:45:12.160 | Why hasn't anybody created an at-home

01:45:14.580 | or pseudo at-home solution,

01:45:16.680 | like a clinic where you can go and pay 50 bucks or 100 bucks

01:45:19.740 | and see if you have any tumors growing in your body?

01:45:21.340 | - Yeah, it's still expensive.

01:45:22.940 | You can get your doctor to try to get you in.

01:45:26.360 | There's some companies that offer blood tests

01:45:28.380 | that look at circulating DNA that'll measure it.

01:45:31.580 | We're getting there.

01:45:32.420 | We're still probably five to 10 years away

01:45:34.020 | from being really cheap.

01:45:35.580 | You can do things like a colon cancer test at home.

01:45:40.460 | I think it's a hundred and something dollars.

01:45:42.660 | You ship off your shit, excuse my language,

01:45:46.160 | and they measure it.

01:45:47.620 | And they tell you if you've got colon cancer

01:45:50.400 | with high probability.

01:45:51.980 | I did that during the pandemic

01:45:54.000 | because I didn't want to get a colonoscopy.

01:45:56.240 | - Is it more accurate or as accurate as a colonoscopy?

01:45:58.860 | - I believe it's close to being as accurate.

01:46:01.000 | The downside is that during a colonoscopy,

01:46:03.240 | they can pinch off the polyps that are looking dangerous,

01:46:06.580 | whereas this obviously isn't that.

01:46:08.740 | But it's certainly easier to do.

01:46:10.440 | And my father, who's Australian,

01:46:12.940 | tells me that it's free for Australians.

01:46:14.820 | They get this test routinely.

01:46:17.160 | - Interesting.

01:46:19.020 | I want to return to the topic that I took us away from,

01:46:22.660 | so I apologize, which is behavioral protocols.

01:46:25.780 | Do you regularly do the cold shower thing,

01:46:28.320 | ice baths, cold water swims?

01:46:29.960 | Are you into that whole biz?

01:46:32.220 | - (laughs)

01:46:34.320 | Well, you do know that I've done it at least once

01:46:37.040 | 'cause we did it together.

01:46:38.000 | - That's right.

01:46:38.840 | Not the same bath, just to be very clear.

01:46:40.760 | Same sauna, different ice bath.

01:46:42.760 | The idea of Sinclair and Huberman

01:46:44.520 | taking an ice bath together is,

01:46:46.340 | it might warm some people's hearts,

01:46:48.040 | but just to be very clear,

01:46:50.480 | same ice bath, different times.

01:46:53.740 | - Yeah.

01:46:54.580 | Thank you for clarifying.

01:46:56.160 | I don't do them regularly.

01:46:58.600 | I do try to sleep cool.

01:47:01.340 | I sleep better anyway.

01:47:04.040 | I try to dress without a lot of warm clothes.

01:47:07.280 | I'm here in a t-shirt and it's middle of summer,

01:47:09.480 | but in winter, I'll try to wear a t-shirt too.

01:47:12.080 | - So you're challenging your system to thermoregulate.

01:47:14.920 | - Right, right.

01:47:16.000 | I've got this hypothesis with Ray Cronus.

01:47:18.920 | We published what's called the metabolic winter hypothesis,

01:47:21.500 | which is, tens of thousands of years ago,

01:47:24.760 | we were either hungry or cold or both,

01:47:27.080 | and we rarely experienced that now.

01:47:29.080 | And so we try to give ourselves the metabolic winter.

01:47:32.640 | And part of the problem, I think,

01:47:33.760 | with the obesity epidemic is that we're never cold.

01:47:37.000 | And cold, when you're cold, you have to burn energy.

01:47:38.960 | It may be only slightly.

01:47:40.600 | But over the whole night, if you're a little bit cool,

01:47:42.880 | you'll actually expend more energy.

01:47:44.300 | So I try to do that.

01:47:45.760 | But I'm not a big fan of cold showers.

01:47:48.360 | The sauna, I don't have access to my gym as much as I did.

01:47:52.040 | But I do want to get back into it.

01:47:53.280 | I used to do it regularly with my son,

01:47:55.800 | and I posted on Instagram once

01:47:57.520 | that he could stay in there for 15 minutes,

01:47:59.120 | and I could only stay in for about three.

01:48:01.800 | Anyway, long story short,

01:48:02.940 | I try to compensate with changes in my diet and exercise

01:48:06.000 | until I get back into it.

01:48:07.440 | - You reminded me of something that I meant to ask earlier,

01:48:10.360 | that obesity reduces NAD levels and accelerates aging.

01:48:14.240 | How?

01:48:16.200 | I mean, okay, so again, this is the scientist in us.

01:48:21.200 | So someone's carrying a lot of excess adipose tissues,

01:48:24.340 | subcutaneous and visceral fat.

01:48:27.060 | But why should that reduce NAD in any ways

01:48:31.860 | that are independent of effects on glucose and insulin?

01:48:34.760 | Is there something direct about white adipose tissue?

01:48:38.200 | And the reason I ask this

01:48:40.320 | is not simply to dig into mechanism alone,

01:48:43.160 | but I think there are really interesting data now

01:48:45.100 | that fat actually gets neural innervation.

01:48:47.440 | I mean, it's not just stored fuel.

01:48:51.760 | It's stored fuel that's acting as an endocrine organ,

01:48:54.940 | essentially.

01:48:55.780 | So yeah, why would being fat make people age faster?

01:49:00.520 | - Yeah, that's a question that is so obvious,

01:49:04.640 | but so few people ask it.

01:49:06.220 | That's what makes you a good scientist.

01:49:08.540 | And so that we don't know,

01:49:09.780 | but I'll give you my best answer,

01:49:11.380 | which is that obesity comes along with a lot of problems

01:49:15.740 | that include a lot of senescent cells in fat.

01:49:20.060 | If you stain old fat for senescent cells, it lights up.

01:49:24.320 | And when you kill off those cells,

01:49:26.520 | at least in mice and maybe in humans it looks like,

01:49:29.820 | the fat is less toxic to the body

01:49:32.100 | 'cause those senescent cells in the fat

01:49:33.700 | are secreting these inflammatory molecules

01:49:35.980 | that will accelerate aging as we now know.

01:49:38.860 | You talk about the sirtuins and NAD.

01:49:41.900 | So if we just look philosophically at why this would be,

01:49:47.720 | the sirtuins only like to come on

01:49:49.940 | or get activated when the body is under adversity.

01:49:54.940 | And if a cell is surrounded by fat or contains a lot of fat,

01:49:59.740 | it's gonna think times are good, doesn't need to switch on.

01:50:02.180 | So that's the evolutionary argument.

01:50:05.100 | Mechanistically, we don't know,

01:50:07.300 | but it could have something to do

01:50:08.520 | with the response to glucose,

01:50:10.380 | which then responds to the sirtuin gene.

01:50:13.340 | But that hasn't been worked out very well.

01:50:15.180 | - And is there any evidence

01:50:16.340 | that leptin, this hormone from fat,

01:50:17.940 | can actually interact with the sirtuin pathway?

01:50:21.300 | - I don't recall seeing that.

01:50:23.620 | - Maybe I could do a sabbatical in your lab

01:50:25.240 | and that'd be a fun one.

01:50:26.900 | - Definitely.

01:50:27.740 | - Because leptin during development

01:50:29.200 | is what triggers the permission

01:50:31.160 | for the hypothalamus to enter puberty, right?

01:50:33.820 | - Yeah.

01:50:34.660 | - This is why kids that eat a lot when they're young

01:50:36.620 | and get overweight will also start to go

01:50:38.900 | and undergo puberty more quickly,

01:50:40.340 | although they have reproductive issues later.

01:50:43.280 | - Well, yeah, we should study the hypothalamus together

01:50:46.140 | because the hypothalamus can control the aging of the body.

01:50:50.220 | - The most interesting part of the brain.

01:50:52.300 | - For sure.

01:50:53.140 | - Yeah, absolutely.

01:50:53.960 | - If you turn on the sirtuin gene,

01:50:55.540 | the sirtuin gene that we work on in the hypothalamus,

01:50:57.940 | it actually will extend lifespan.

01:50:59.820 | Also, it's been shown by Dongxin Cai

01:51:02.340 | at Albert Einstein College of Medicine

01:51:04.060 | that if you inhibit inflammation

01:51:06.100 | in the hypothalamus in a mouse,

01:51:08.180 | it will increase or maintain the expression

01:51:11.900 | of what's called GnRH,

01:51:13.380 | which is the hormone that he found actually controls

01:51:16.580 | longevity in the mouse in part.

01:51:18.540 | And so keeping inflammation down in the hypothalamus

01:51:21.260 | is sufficient to extend the lifespan of animals.

01:51:23.860 | And I reviewed that paper for Nature about seven years ago.

01:51:27.760 | And that was the first demonstration

01:51:29.260 | that the hypothalamus is one of the leading regulators

01:51:32.360 | of the body's age.

01:51:33.460 | - I find this fascinating.

01:51:34.440 | GnRH, for those of you that don't know,

01:51:37.100 | actually comes from neurons in the hypothalamus

01:51:39.220 | that then literally reach down into the pituitary

01:51:42.260 | and trigger the release of all the things

01:51:43.660 | that control fertility,

01:51:45.260 | luteinizing hormone, follicle stimulating hormone, et cetera.

01:51:48.660 | It's such a powerful set of neurons,

01:51:50.180 | and it's never really been clear

01:51:51.940 | what at a behavioral level triggers the release of GnRH.

01:51:55.740 | There's all the stories about pheromones

01:51:57.540 | and timers and puberty, et cetera,

01:51:59.320 | but environmental conditions and dietary conditions

01:52:02.420 | and behaviors that can control GnRH release,

01:52:05.020 | I think is an incredible area for exploration.

01:52:10.140 | I'd love to do that sabbatical, by the way.

01:52:12.460 | I have a couple seemingly random questions,

01:52:16.200 | but I can't help but ask,

01:52:17.380 | because one thing I like to do is forage the internet

01:52:20.140 | for practices that at least more than a few people are doing

01:52:23.640 | and then wonder whether or not there's any basis for it.

01:52:26.400 | You mentioned methylation as a detrimental process,

01:52:31.540 | the way it disrupts the epigenome,

01:52:33.820 | the CD reader, so to speak.

01:52:36.540 | There are people out there who are ingesting methylene blue.

01:52:40.320 | And when I was a kid,

01:52:41.540 | I used methylene blue to clean my fish tank.

01:52:44.580 | And I love fish tanks.

01:52:45.840 | I know you're into aquaria also.

01:52:47.700 | A different podcast episode, talk about aquaria,

01:52:50.940 | but why in the world would people ingest methylene blue?

01:52:55.940 | Meaning, is their logic correct?

01:52:58.320 | And/or is that a dangerous practice?

01:53:01.180 | I'm not sure I'd want to ingest methylene blue.

01:53:04.160 | Sounds like a bad thing to do.

01:53:06.460 | - It stains your body.

01:53:07.640 | You've seen these people turn blue.

01:53:09.720 | - Yeah, there was someone in my lab as a postdoc

01:53:13.400 | was using it to study a completely different process

01:53:16.380 | related to the blood-brain barrier

01:53:17.560 | and used to inject into animals and they would turn blue.

01:53:20.460 | But then again, people ingest colloid silver.

01:53:22.960 | You know, they'll put in there.

01:53:23.800 | There's this, please, people don't do this.

01:53:25.840 | Or if you do, just don't tell me 'cause I won't like it.

01:53:30.100 | People put it in their eyes.

01:53:32.220 | And some people actually stain their skin.

01:53:34.520 | They actually become kind of this silver, purple,

01:53:37.300 | brown color if they do it excessively.

01:53:39.620 | I mean, there's a lot of crazy stuff out there.

01:53:42.040 | But what do you think they're thinking

01:53:44.380 | with this methylene blue thing?

01:53:45.580 | Or should we just get them to a good psychiatrist?

01:53:48.020 | - I don't know for sure.

01:53:51.740 | I think methylene blue was found to extend the lifespan

01:53:53.880 | of some lower organism and that's where it came from.

01:53:56.760 | My recollection with the-

01:53:58.200 | - This is on lower organisms.

01:53:59.780 | - Yes, smaller organisms.

01:54:02.420 | I think doesn't, do you remember, Andrew,

01:54:04.380 | does it interrupt or interfere with mitochondrial activity?

01:54:07.680 | And that's why we're doing it.

01:54:09.740 | Yeah, we need to look this up and post it.

01:54:13.020 | We'll get to the bottom of this.

01:54:14.440 | But those methyls, let's talk about those.

01:54:17.420 | Those methyls have to be placed

01:54:18.780 | on the right part of the genome.

01:54:21.260 | They get attached to the right genes and the wrong genes.

01:54:23.340 | And if you have a lot of methylation,

01:54:26.060 | it's going to mess up the epigenome.

01:54:28.660 | Smoking will do that, lack of exercise, all that good stuff.

01:54:32.300 | So what you actually want to do is you want to measure it

01:54:34.820 | and make sure what you're doing with your body is working.

01:54:38.240 | How do you know that if you do this

01:54:40.000 | or that is actually helping?

01:54:41.960 | And so you can test your age.

01:54:43.640 | I could take a swab from your mouth

01:54:45.820 | and tell you how old you are biologically.

01:54:48.180 | And then we could work on trying to bring that down.

01:54:50.380 | And actually there are anecdotes now

01:54:53.420 | that people are reversing their age by a decade or more

01:54:57.140 | just by doing some of the things that we've talked about

01:55:00.340 | and some other cutting edge stuff

01:55:02.240 | that I'm going to write about.

01:55:04.600 | But yeah, but you have to measure stuff.

01:55:07.340 | That's, I didn't want to forget to bring that up.

01:55:10.620 | I'm measuring stuff all the time.

01:55:11.980 | I have blood tests like you.

01:55:14.100 | I've got this monitor that's stuck to my chest right now

01:55:16.500 | that's measuring myself a thousand times a second.

01:55:18.980 | And I measure my biological age.

01:55:20.660 | - What's it measuring a thousand times a second?

01:55:22.860 | A huge host of things?

01:55:24.060 | - Yeah, yeah, yeah.

01:55:24.900 | So this little device is stuck here

01:55:26.680 | and it's for two weeks that you just recharge it

01:55:29.500 | or send it back and get a new one.

01:55:30.800 | It's got a body temperature movement,

01:55:33.360 | heart rate variability.

01:55:34.620 | It's an FDA approved device.

01:55:36.340 | It's not a toy.

01:55:37.180 | It's not one of these recreational things.

01:55:40.540 | It also listens to my voice.

01:55:42.480 | Eventually it'll tell me if I need a psychiatrist

01:55:44.780 | or if I'm depressed.

01:55:46.420 | It will tell me how I sleep, obviously.

01:55:49.680 | But when you put all that data together

01:55:51.060 | and it's individualized and anonymized,

01:55:54.380 | it can now tell my doctor in real time

01:55:56.920 | if I've got a cold that needs an antibiotic

01:55:59.360 | or it's just a virus,

01:56:01.120 | if I am suffering from COVID-19

01:56:06.120 | or even if I'm gonna have a heart attack next week.

01:56:09.800 | And so these little devices

01:56:11.000 | are going to be with us all the time

01:56:13.320 | instead of going to your doctor once a year,

01:56:14.880 | which is ludicrous.

01:56:16.040 | - I have to ask you about x-rays.

01:56:19.880 | 'Cause every time I go through the scanner at the airport,

01:56:22.280 | I think Sinclair would never do this.

01:56:24.820 | And the argument I heard you give about this before

01:56:27.860 | was a really excellent one,

01:56:29.080 | which is that it's a low level amount of radiation

01:56:33.820 | going through at the airport,

01:56:35.160 | but the argument is always,

01:56:37.000 | well, it's just as much as on the plane.

01:56:38.700 | And your argument, your counter argument, I should say was,

01:56:42.180 | well, then why would I want to do both, right?

01:56:45.080 | So when you go to the airport,

01:56:47.160 | assuming you're not running late

01:56:48.560 | and you have to go through the standard line,

01:56:50.580 | what do you say to them?

01:56:52.240 | And do you say, "I'm David Sinclair,"

01:56:54.160 | and then they shuttle you to your own line?

01:56:56.840 | What do you say?

01:56:57.680 | You do say, "I don't like this thing."

01:56:59.400 | Do you have to give them a reason?

01:57:01.580 | - No, you don't.

01:57:02.420 | You can say, "I don't want this,"

01:57:04.440 | and they'll get annoyed

01:57:05.360 | 'cause it's hard for them to pat you down.

01:57:08.260 | But you get a pat down and you're done.

01:57:09.760 | As long as you're not in a hurry, it's fine.

01:57:12.480 | If you want to pay for the TSA Pre in America

01:57:14.840 | or the way to get around those scanners, you can do that.

01:57:17.320 | So I travel a lot, so it's worth it anyway.

01:57:20.080 | But I just go through the metal detector.

01:57:21.640 | I don't get scanned.

01:57:22.880 | - And the metal detector doesn't have the same problem.

01:57:26.440 | And what about x-rays at the dentist?

01:57:28.400 | - Yeah.

01:57:29.240 | Well, one x-ray is not going to kill you.

01:57:31.200 | Two is not going to kill you.

01:57:32.360 | But I'd rather- - Three will kill you.

01:57:33.680 | No, I'm just kidding.

01:57:35.280 | - I try to limit it because it's cumulative.

01:57:38.040 | And I went for six years without having a dental x-ray.

01:57:42.280 | And then my last visit, I just gave up.

01:57:45.080 | I was tired of arguing with my dentist.

01:57:47.400 | So they gave me one, but they've got lead coats on

01:57:50.100 | and they put lead all over your body.

01:57:52.360 | That's telling you something right there.

01:57:54.400 | And funnily enough, my teeth hadn't changed.

01:57:58.440 | Now, you could balance that by saying,

01:58:00.260 | well, one x-ray, two x-rays, three x-rays

01:58:02.440 | is worth it if I have cavities.

01:58:04.640 | And that's true.

01:58:05.480 | You want to know what's in there.

01:58:07.260 | But doing it regularly, for me, I don't think was worth it

01:58:11.600 | because my teeth were in perfect health

01:58:13.140 | and have always been, don't have any cavities,

01:58:16.220 | didn't have braces, they're fine.

01:58:17.700 | So stop scanning me.

01:58:18.840 | I mean, I know you have to pay for the machine,

01:58:20.600 | but do I have a choice?

01:58:22.420 | Yes, so stop pressuring me.

01:58:24.800 | - You know, who shared your sentiments about x-rays

01:58:26.940 | and the dentist in general,

01:58:28.600 | my apologies to the dentists out there,

01:58:30.720 | was the great physicist, Richard Feynman.

01:58:32.880 | This is a story about him that's not especially well known,

01:58:36.500 | but he had very serious health concerns about x-rays

01:58:41.500 | because he understood the physics

01:58:44.180 | and he understood enough biology

01:58:45.560 | that he was actually quite vocal about his dislike

01:58:49.740 | of dental technology and its dangers.

01:58:52.720 | And he talked about some of that.

01:58:54.520 | People can find that on the internet if they like.

01:58:58.600 | Speaking of people who are like Feynman,

01:59:02.680 | who've been engaged in public discourse about science,

01:59:06.140 | one of the things that I appreciate about you,

01:59:07.920 | in fact, the way that you and I initially came

01:59:10.760 | to know one another is through

01:59:12.480 | your public health education efforts.

01:59:15.840 | So obviously we're doing this podcast,

01:59:19.320 | you've done the Joe Rogan podcast,

01:59:20.880 | Lex Friedman's podcast, excuse me, Lex,

01:59:23.640 | I'm still adjusting that,

01:59:24.660 | Lex Friedman podcast and many other podcasts,

01:59:28.860 | you've written an amazing book.

01:59:30.360 | What are you thinking these days

01:59:33.140 | in terms of what the world needs

01:59:35.760 | in terms of education from scientists,

01:59:39.480 | education from MDs, education in general

01:59:43.160 | as it relates to these things?

01:59:44.320 | Because I think if nothing else,

01:59:47.240 | 2020 revealed to us that there's a gap,

01:59:50.640 | there's a gap in understanding

01:59:52.480 | and that the scientists too are guilty

01:59:54.360 | of not knowing what to do with all the information

01:59:57.960 | that's out there on PubMed or elsewhere.

01:59:59.960 | What are you thinking for yourself?

02:00:03.240 | And in general, I'd like to just know,

02:00:04.880 | what do you think the world needs there?

02:00:06.360 | Maybe we can recruit some more public educators.

02:00:09.680 | - Yeah, well, we've gone from a time

02:00:12.880 | when you and I were in college and young professors,

02:00:16.780 | where the only way to get our voice out to the public

02:00:20.000 | was either through a newspaper

02:00:22.100 | or a very short radio interview,

02:00:24.740 | which for me was extremely frustrating

02:00:27.800 | 'cause particularly the newspapers and my topic,

02:00:31.060 | every time was twisted into something

02:00:32.760 | that was not just embarrassing,

02:00:34.520 | but Harvard University used to bring me into the back office

02:00:37.380 | and slap my wrist. - Frankenstein.

02:00:39.040 | - How did you say such a thing?

02:00:40.560 | We're all gonna live 200, I didn't say that.

02:00:42.940 | So we're now also in a world

02:00:45.600 | where we're overwhelmed with information

02:00:47.640 | and most of it is wrong

02:00:49.800 | and anyone can pretend to be an expert.

02:00:52.180 | So we've gone from early days to now, the future,

02:00:56.760 | and we're experiencing it right now,

02:00:58.800 | thanks to guys like you, people like you,

02:01:01.320 | is that the experts, some experts,

02:01:03.600 | a small number who are brilliant and good communicators,

02:01:07.560 | are talking directly to the public.

02:01:09.400 | This has never been able to be possible

02:01:12.200 | until this time right now.

02:01:15.520 | So another five years from now, and certainly by 10 years,

02:01:19.540 | I would hope that there are trusted sources of information

02:01:23.200 | of people who can not just communicate the ideas directly,

02:01:28.200 | but are able to talk about things that are going on

02:01:31.760 | that aren't even published yet to say,

02:01:33.760 | here's what's really going on

02:01:35.700 | and this is what the future looks like,

02:01:38.000 | but this is somebody like yourself

02:01:39.600 | who spent their whole life studying a particular topic

02:01:42.960 | and knows what they're talking about.

02:01:45.360 | And this is also something

02:01:46.920 | that I think most people don't know,

02:01:49.520 | that we scientists, if we tell a lie, we burst into flames.

02:01:53.300 | We absolutely cannot tell something that's untrue

02:01:56.960 | and to the best of our knowledge, we say it as it is,

02:01:59.880 | because if we don't, we're beaten up

02:02:02.040 | or we kicked out of the university.

02:02:04.480 | So the people who survive to our age,

02:02:06.760 | and I'm a little older than you,

02:02:07.800 | so I've survived a bit longer.

02:02:09.420 | - But a lot younger inside.

02:02:11.120 | - No, but we have to measure you with my-

02:02:12.760 | - Yeah, we need to see, I probably need a little help,

02:02:14.960 | but hopefully not too much.

02:02:15.920 | - We'll measure that and we'll work on your eating.

02:02:19.480 | But this is really, really important is that finally,

02:02:23.000 | people like you are allowed by our universities

02:02:25.420 | to talk to the public.

02:02:26.960 | I used to do it with a real threat to my survival.

02:02:30.720 | People would look at me, oh, he's a salesman,

02:02:32.640 | he's promoting this and that.

02:02:33.760 | It was seen as a real negative.

02:02:35.460 | But finally, I think we're in a world

02:02:36.740 | where it's not negative anymore.

02:02:38.620 | And the pandemic showed that we needed voices of reason,

02:02:42.360 | voices of fact that you could trust.

02:02:45.480 | And you can see the popularity of your podcast

02:02:48.560 | shows that the public, they're desperate for facts

02:02:52.120 | that they can trust

02:02:52.960 | 'cause they don't know what to believe anymore.

02:02:55.760 | - Well, I am being completely honest when I say this,

02:02:59.520 | that I followed your lead.

02:03:01.280 | I saw you on the Joe Rogan podcast and my jaw dropped.

02:03:04.760 | I was like, this is amazing.

02:03:07.280 | Because he had had other good scientists on before,

02:03:10.040 | but you're a tenured professor, Harvard genetics,

02:03:13.080 | department of genetics.

02:03:14.720 | And for those of you who don't know,

02:03:16.480 | there's Harvard and of course, Harvard Medical School,

02:03:20.440 | and they're both excellent, of course,

02:03:23.640 | but these are the top, top tiers of academia.

02:03:26.400 | And I certainly understand what it takes

02:03:27.920 | to get there and survive there and to thrive there.

02:03:30.720 | It's like a game of pinball.

02:03:32.360 | You never win, you just get to,

02:03:34.520 | if you're doing really well, you get to keep playing.

02:03:36.640 | That's the truth in academia.

02:03:38.640 | And if you're not, you stop playing basically.

02:03:40.960 | But when I saw you explain what you were doing

02:03:45.080 | in a way that was accessible to people

02:03:47.040 | and also talking about possible protocols

02:03:49.680 | that they might explore for themselves

02:03:51.320 | to see if those were right for them,

02:03:53.840 | I was just dazzled and excited.

02:03:57.080 | And I made every effort to get in contact with you

02:03:59.400 | and the rest is history.

02:04:02.240 | But I think what's really exciting to me these days

02:04:05.640 | is because of 2020 and everything that's happened

02:04:08.320 | and it continues to happen, there's a thirst for knowledge.

02:04:12.240 | There's also this direct to the public route

02:04:15.380 | that you mentioned.

02:04:16.640 | And I think there's also an openness,

02:04:20.860 | I'd love your thoughts on this,

02:04:21.720 | but it seems to me that there's an openness

02:04:24.500 | from the general public about health practices,

02:04:28.800 | that there are actually things that people can do

02:04:30.720 | to control their stress level, to control their sleep,

02:04:34.480 | to control their cholesterol,

02:04:36.440 | if that's what they need to do, maybe they don't,

02:04:39.020 | and to even control their lifespan,

02:04:41.800 | which I think is remarkable.

02:04:43.780 | And I know I speak on behalf of so many people

02:04:47.060 | when I just, I want to say thank you.

02:04:48.640 | You've truly changed the course of my life.

02:04:51.300 | I would not be sitting here doing this

02:04:53.240 | were it not for your example.

02:04:55.300 | And I always say, Sinclair, many people have written books,

02:04:58.740 | many academics have written books as you have,

02:05:01.180 | but in terms of doing podcasts

02:05:02.700 | and really getting out there with your message

02:05:04.380 | in a way that I have to assume raised your cortisol level

02:05:07.100 | and heart rate just a little bit,

02:05:08.820 | but you did it nonetheless.

02:05:12.580 | You know, you were truly first man in,

02:05:14.660 | and that deserves a nod,

02:05:17.220 | and I have a great debt of gratitude to you for that.

02:05:19.840 | So thank you so much.

02:05:20.940 | - Thanks, Andrew, you've become a good friend,

02:05:23.300 | and I'm super proud of what you've done

02:05:25.260 | and I know what you will do.

02:05:27.260 | - So in addition to your book and your presence

02:05:30.380 | on social media, Instagram and Twitter,

02:05:32.740 | and appearances on podcasts,

02:05:34.640 | recently I've noticed that you've opened up

02:05:37.820 | a sort of an email/website that people can access, excuse me,

02:05:42.820 | to get some information about their own health

02:05:45.660 | and rates of aging.

02:05:46.780 | Tell us about that and what's being measured

02:05:49.420 | and what is this test that you've been working on

02:05:53.140 | secretly and now soon not so secretly?

02:05:56.500 | - Yeah, well, what I want is a credit score for the body

02:06:00.400 | to make it easy for people to follow their health.

02:06:03.660 | And there is a number,

02:06:05.020 | there's a biological age that you can measure.

02:06:06.900 | Unfortunately, the test is many hundreds of dollars

02:06:08.900 | right now, but in my lab,

02:06:10.940 | we've been able to bring that down a lot.

02:06:13.740 | And so I want to democratize this test

02:06:15.420 | so that everybody has access to a score for their health

02:06:18.080 | that can predict not just their future health

02:06:22.060 | and time of death, but to change it.

02:06:24.740 | And I'm building a system that will point people

02:06:27.660 | in the right direction and give them discounts

02:06:29.500 | for certain things that will improve

02:06:31.780 | not just their health now,

02:06:33.540 | but 10, 20, 30 years into the future.

02:06:35.660 | And we can measure that and very cheaply keep measuring it

02:06:38.660 | to know that you're on the right track.

02:06:40.420 | 'Cause if you don't measure something,

02:06:41.500 | you can't optimize it.

02:06:42.860 | And so this is the biological age test.

02:06:44.640 | We've developed it.

02:06:45.480 | It's a simple mouth swab.

02:06:47.660 | We're rolling it out.

02:06:48.980 | We're building the system right now.

02:06:51.020 | And there is a signup sheet

02:06:52.080 | 'cause a lot of people want to get in line.

02:06:54.340 | Go to drsinclair.com.

02:06:56.060 | You can get on that and you'll be one of the first people

02:06:58.780 | in the world to get this test and see what we're doing.

02:07:01.460 | - Fantastic.

02:07:03.220 | Will people be celebrating their biological age birthdays?

02:07:08.020 | In other words, if I'm minus, like if I could imagine,

02:07:10.660 | so I'm 45 right now, soon to be 46.

02:07:12.620 | But if I were to be so lucky as to get my biological age

02:07:15.860 | to 35 within 12 months, maybe can help me do that.

02:07:20.360 | Do I get to celebrate a negative birthday?

02:07:23.920 | - Absolutely.

02:07:24.760 | And my plan is that those people who take their age back

02:07:28.060 | a year or more, we think we can go back 20 years.

02:07:30.820 | Eventually, they'll get a birthday card from me

02:07:33.240 | and it's a negative birthday card.

02:07:35.780 | - I love it.

02:07:36.660 | And probably very little actual birthday cake

02:07:39.480 | being ingested, but who cares?

02:07:41.320 | 'Cause you're living that much longer.

02:07:42.820 | - Well, it's full of stevia.

02:07:43.660 | That'll be fine.

02:07:45.080 | - And thank you for talking to us today.

02:07:47.500 | I realized I took us down deep into the guts of mechanism

02:07:52.500 | and as well, talking about global protocols,

02:07:55.900 | everything from what one can do and take if they choose,

02:07:59.220 | that's right for them, to how to think about

02:08:02.260 | this whole process that we talk about

02:08:05.180 | when we talk about lifespan.

02:08:06.780 | As always, incredibly illuminating.

02:08:10.020 | Thank you, David.

02:08:11.100 | - Thanks, Andrew.

02:08:12.560 | - Thank you for joining me for my conversation

02:08:14.520 | with Dr. David Sinclair.

02:08:16.320 | If you're enjoying and/or learning from this podcast,

02:08:18.940 | please subscribe to our YouTube channel.

02:08:20.980 | In addition, please subscribe on Apple and/or Spotify.

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02:08:26.440 | and you can leave us suggestions

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02:08:31.020 | In addition, on Apple,

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02:08:33.620 | and you can leave us a comment.

02:08:35.520 | Please also check out the sponsors mentioned

02:08:37.320 | at the beginning of this episode.

02:08:38.460 | That's the best way to support this podcast.

02:08:41.100 | Also, I teach science and science-related tools on Instagram.

02:08:44.580 | It's Huberman Lab on Instagram.

02:08:46.180 | I also have a Twitter, which is also Huberman Lab.

02:08:48.740 | So be sure to check those out.

02:08:50.080 | A lot of the material covers things similar to the podcast,

02:08:52.940 | but oftentimes I'll cover unique material

02:08:54.840 | not featured at all on the podcast.

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02:09:06.420 | at any level that you like.

02:09:08.020 | Today and in many other previous episodes

02:09:10.260 | of the Huberman Lab podcast, we discuss supplements.

02:09:12.920 | While supplements aren't necessary or right for everybody,

02:09:16.140 | many people derive tremendous benefit from supplements.

02:09:18.900 | For that reason, we partnered with Thorne, T-H-O-R-N-E,

02:09:22.120 | because Thorne supplements are the absolute highest quality

02:09:25.040 | and the absolute highest precision,

02:09:27.140 | meaning what you see listed on the bottle

02:09:29.000 | is what's actually in the bottle,

02:09:30.320 | which is not the case for many supplement companies

02:09:32.880 | out there.

02:09:33.720 | Thorne is one of the partners of the Mayo Clinic

02:09:36.120 | and all the major sports teams.

02:09:37.400 | And so they really are very trusted, very highest quality.

02:09:40.700 | If you want to see the supplements that I personally take,

02:09:42.940 | you can go to thorne.com/u/huberman.

02:09:46.800 | And there you'll see the supplements that I take.

02:09:48.440 | You can get 20% off any of those supplements.

02:09:50.920 | And if you navigate deeper into the Thorne site

02:09:53.080 | through that portal, you'll also get 20% off

02:09:55.280 | any of the other supplements that Thorne makes.

02:09:57.160 | So again, it's thorne.com/u/huberman

02:10:02.160 | to get 20% off any of the supplements that Thorne makes.

02:10:05.600 | Also take note that the Lifespan podcast

02:10:07.840 | featuring Dr. David Sinclair as a host

02:10:10.080 | launches Wednesday, January 5th.

02:10:11.920 | You can find the first episode here

02:10:13.560 | on the Huberman Lab podcast channel.

02:10:15.400 | They also have their own independent channel.

02:10:17.760 | You can find the link to that channel in the show notes.

02:10:19.860 | So please go there, subscribe on YouTube,

02:10:21.640 | also on Apple and Spotify.

02:10:23.520 | I've seen these episodes, they are phenomenal,

02:10:25.760 | and you're going to learn a tremendous amount

02:10:27.920 | about aging and how to slow and reverse aging

02:10:30.560 | from the world expert himself, Dr. David Sinclair.

02:10:33.840 | And last, but certainly not least,

02:10:35.960 | thank you for your interest in science.

02:10:37.800 | [upbeat music]

02:10:40.380 | (upbeat music)

Dr. David Sinclair: The Biology of Slowing & Reversing Aging | Huberman Lab Podcast #52

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