- Welcome to the Huberman Lab podcast, where we discuss science
and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of
neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Dr. David Sinclair, professor of genetics at
Harvard Medical School and co-director of the
Paul F. Glenn Center for the Biology of Aging. Dr. Sinclair's work is
focused on why we age and how to slow or reverse
the effects of aging by focusing on the cellular
and mole
cular pathways that exist in all cells of
the body and that progress those cells over time from
young cells to old cells. By elucidating the biology of
cellular maturation and aging, Dr. Sinclair's group has
figured out intervention points by which any of us indeed, all of us, can slow or reverse the effects of aging. What is unique about his work is that it focuses on
behavioral interventions, nutritional interventions,
as well as supplementation and prescription drug
interventions that can hel
p us all age more slowly and reverse
the effects of aging in all tissues of the body. Dr. Sinclair holds a unique
and revolutionary view of the aging process, which is that aging is not the normal and natural consequence that we all will suffer. But rather that aging is a disease that can be slowed or halted. Dr. Sinclair continually publishes original research articles
in the most prestigious and competitive scientific journals. In addition to that, he's
published a popular book that was a New
York Times bestseller. The title of that book, is 'Lifespan: Why We Age And Why We Don't Have To.' He is also very active
in public facing efforts to educate people on the biology of aging and slowing the aging process. Dr. Sinclair, and I
share a mutual interest and excitement in public
education about science. And so I'm thrilled to share
with you that we've partnered. And Dr. David Sinclair
is going to be launching the lifespan podcast, which is all about the
biology of aging and tools to int
ervene in the aging process. That podcast will launch
Wednesday, January 5th. You can find it at the
link in the show notes to this episode today as well. You can subscribe to that
podcast on YouTube, Apple, or Spotify, or anywhere
that you get your podcasts. Again, the lifespan podcast
featuring Dr. David Sinclair, Claire begins Wednesday,
January 5th, 2022, be sure to check it out. You're going to learn a
tremendous amount of information, and you're going to learn
both the mechanistic science
behind aging, the
mechanistic science behind reversing the aging
process and practical tools that you can apply in your everyday life. In today's episode, Dr. Sinclair and I talk about the biology of aging and tools to intervene in that process. And so you might view today's episode as a primer for the lifespan podcast, because we delve deep
into the behavioral tools, nutritional aspects,
supplementation aspects of the biology of aging. We also talk about David's
important discoveries of the sir
tuins, particular components that influence what is
called the epigenome. And if you don't know
what the epigenome is, you will soon learn in today's episode. Coming away from today's episode, you will have in-depth knowledge
about the biology of aging at the cellular, molecular, and what we call the circuit level, meaning how the different
organs and tissues of the bodies age independently, and how they influence the aging of each other. Today's episode gets into discussion about many aspects o
f aging and tools to combat aging that have not been discussed
on any other podcasts or in the book lifespan. Before we begin, I'd like to
emphasize that this podcast is separate from my teaching
and research roles at Stanford. It is however part of my desire and effort to bring zero cost to consumer
information about science and science related tools
to the general public. In keeping with that theme,
I'd like to thank the sponsors of today's podcast. Our first sponsor is ROKA. ROKA makes eyegla
sses and sunglasses that are the absolute highest quality. I've spent a lifetime
working on the visual system. And I can tell you that the visual system has to contend with a number
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things in your visual system so that you can still see things clearly. One problem with a lot of
eyeglasses and sunglasses is they don't take that
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and enter the code Huberman at checkout. Today's episode is also
brought to us by InsideTracker. InsideTracker is a
personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long
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getting regular blood work done for the simple reason
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to get 25% off any of InsideTracker's plans. Just use the code Huberman at checkout. Again, that's insidetracker.com/huberman
to get 25% off any of InsideTracker's plans. Today's episode is also
brought to us by Magic Spoon. Magic Spoon is a zero sugar, grain-free, keto friendly cereal. Now I don't follow a
strictly ketogenic diet. What works best for me is to eat according to my desire to be alert
at certain times of day and to be sleepy at other times of day. So for me, that mean
s
fasting until about 11:00 AM or 12 noon most days. And then my lunch is typically
a low carb, ketoish lunch, maybe a small piece of grass-fed meat, some salad, something of that sort. And then in the afternoon,
I might have a snack that's also ketoish. And then at night is when
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polo cinnamon on there. I'm getting hungry just talking about it. Now, if you want to try Magic Spoon, you can go to magicspoon.com/huberman to grab a variety pack. Use the promo code Huberman at checkout, to get $5 off your order. Again, that's magicspoon.com/huberman and use the code Huberman to get $5 off. And now my conversation
with Dr. David Sinclair. Thank you for coming. - Thanks for having me here. It's good to see you. -
This is mate by the way, that
we're toasting at 11:00 AM. Unlike other podcasts, we,
well, I don't drink alcohol, so I'm boring that way. But truly, thanks for being here, I have a ton of questions for you. We go way back in some sense, but that doesn't mean that I don't have many, many questions about
aging, longevity, lifespan, actionable protocols to increase how long we live, et cetera. And I just want to start off
with a very simple question. I'm not even sure there's an answer to, but what
is the difference
between longevity, anti-aging and aging as a disease? Because I associate
you with the statement, aging is a disease. - Right? Well, so longevity is
the more academic way we describe what we research. Anti-aging is kind of the same thing, but it's got a bad rap
because it's been used by a whole bunch of people that don't know what they're talking about. So I really don't like
that term anti-aging, but aging is a disease and longevity are perfectly valid ways
to talk about this
subject. So let's talk about aging as a disease. When I started my research, disease here at Harvard Medical School, it was considered, if there's something
that's wrong with you. and it's a rare thing, it has to be less than
50% of the population, that's definitely a disease, and then people work their whole lives to try and cure that condition. And so I looked up, what's the definition of aging and it says, well, it's
a deterioration in health and sickness and you can die
from it, typically y
ou do. Something that sounds
pretty much like a disease, but the caveat is that if
more than half the population gets this condition, aging,
it's put in a different bucket. Which is first of all, that's outrageous, 'cause it's just a
totally arbitrary cutoff. But think about this, that we're ignoring the major
'cause of all these diseases. Aging is 80 to 90% the cause
of heart disease, Alzheimer's. If we didn't get old and
our bodies stayed youthful, we would not get those diseases. And actually
what we're
showing in my lab is, if you turn the clock back, in tissues, those diseases go away. So aging is the problem
and instead through, most of the last 200 years, we've been sticking band-aids on diseases that have already
occurred because of aging and then it's too late. So there are a couple of things. One is we want to slow aging down so we don't get those diseases
and when they do occur, don't just take a bandaid on, reverse the age of the body and then the diseases will go away. - T
hat clarifies a lot for me, thank you. Can we point to one specific
general phenomenon in the body that underlies aging? - Yeah, well, that's contentious because scientists like to
come up with new hypothesis. It's how they build their careers. But fortunately during the two thousands, we settled on eight or
nine major causes of aging. We call them hallmarks 'cause causes was a little bit too strong, but these eight or nine causes, at least for the first time
allowed us to come around and talk t
ogether. And we put them on a pizza so everyone got an equal
weighting, equal slices. But before that, by the way, we were trying to kill
each other in the field, that was horrible. - Interesting that you guys work on aging and you're trying to kill each other. - Yeah, isn't it? Well kill each other's careers. Well I like to think
I was fairly generous, but I was one of the kids and the old guard really
didn't like the new guard. We just came along in the 1990s and said, free radicals don't do m
uch. They're actually genes
called longevity genes. And that caused a whole ruckus. And there was this competition
for what never happened, which was a Nobel prize for this. And it just led to a lot of competition. I would go to meetings and
people would shout at each other and backstab, it was horrible. But then unfortunately
in the two thousands, we rallied around this new map of aging with these causes of hallmarks. But I think that there's
one slice of the pizza that is way larger than the o
thers. And we can get to that, but that's the information in the cell that we call the epigenome. - Well tell us a little bit
more about the epigenome, frame it for us if you will,
and then we'll get into ways that one can adjust the
epigenome in positive ways. - Yeah, so in science, what I like to do, a reductionist is to boil it down and I actually ended up boiling, aging down to an equation, which is the loss of
information due to entropy. It's a hard thing to overcome,
second law of thermody
namics. That's fair, but this
equation really represents the fact that I think aging
is a loss of information in the same way that
when you xerox something, a thousand times you'll
lose that information or you try to copy a cassette tape. Or even if you send information
across the internet, some of it will get lost. That's what I think is aging. And there were two types
of information in the body. There is the genetic
information, which is digital. ATCG the chemical letters of DNA, but there's t
his other part of
the information in the body. that's just as important,
it's essential, in fact, and that's the systems
that control which genes are switched on and off
in what cell at what time in response to what we eat, et cetera. And it turns out that 80% of
our future longevity and health is controlled by the second part, the epigenetic information,
the control systems. I liken the DNA to the
music that's on a DVD or a compact disc for the younger people. We used to use these things. - I r
ecall. - Yeah, and then the epigenome
is the reader that says, okay, in this cell we need
to play that set of songs and in this other cell, we have to play a different set of songs. But over time, aging is the
equivalent of scratching, the CD and the DVD so that you, you're not playing the
right songs and cells when they don't hear the right songs, they get messed up and
they don't function well. And that is what I'm saying
is the main driver of aging. And these other hallmarks
are largely manif
estations of that process. - Can we go a little deeper into what that these scratches are. Is it the way that the DNA
are packed into a cell? Is it the way that they're spaced? What are the scratches
that you're referring to? - So DNA is six foot long. So if you join your chromosomes together, you get a six foot post-sale. So there's enough to go to
the moon and back eight times in your body. And it has to be wrapped
up to exist inside us, but it's not just wrapped up willy-nilly. It's not just
a bundle of string, it's wrapped up very carefully in ways that dictates which genes
are switched on and off. And when we're developing in the embryo, the cell marks the DNA
with chemicals that says, okay, this gene is for a nerve cell. Your cell will stay a nerve cell for the next a hundred
years, if you're lucky. Don't turn into a skin
cell that would be bad. And those chemicals, there are many different
types of chemicals, but one's called methylation. Those little menthols will
mark which so
ngs get played for the rest of your life. And there are other that change daily. But in total, what we're
saying is that the body controls the genome through
the ability to mark the DNA and then compact some parts
of it, silence those genes, don't read those genes and
open others, keep others open that should stay open. And that pattern of genes
that are silent and open, silent, open, is what
dictates the cells type the cells function. And then the scratches are
the disruption of that. So genes
that were once
silent and you could say, it's a gene that is involved in skin. It's starting to come on in
the brain, shouldn't be there, but we see this happen and vice versa, the gene might get shut
off over time during aging. Cells over time, lose these structures, lose their identity, they forget what they're supposed to do and we get diseases. We call that aging and
we can measure that. In fact, we can measure it in such a way that we can predict when
somebody is going to die based on the c
hanges in those chemicals. - Are these changes, the
same sorts of changes that underlie the outward
body surface manifestations of aging, that most of
us are familiar with, graying of the hair,
wrinkling of the skin, drooping of the face. Walking around New York lately, it's amazing to me,
there are certain people that seem to walk looking
down at the sidewalk because their spine is
essentially in a C shape, right? A hallmark, if you will, of aging, that most of us are familiar with. Are the sam
e sorts of DNA
scratches associated with that? Or are we talking about people that are potentially
are going to look older, but simply live longer? - Well, it's actually, you
are as old as you look, if you want to generalize. So let's start with centenarian families. These are families that
tend to live over a hundred. When they're 70, they
still look 50 or less. So it is a good indicator. It's not perfect because you can like me
growing up in Australia and accelerate the aging of your skin. But
in general, how you look, and no one's ever died from gray hair, but overall you can get a sense just from the ability of
skin to hold itself up, how thin it is, the number of wrinkles. A great paper just came out that said that an AI System looking at the face could very accurately
predict someone's age. - Very interesting. So I started off in
developmental neurobiology. So one of the things
that I learned early on that I still believe wholeheartedly is that development doesn't
stop at age 12
or 15 or even 25 that your entire life is
one long developmental arc. So in thinking about different portions of that developmental arc,
the early portion of infancy, and especially puberty, seem
like especially rapid stages of aging. And I know we normally
look at babies and children and kids in puberty, and we
think, oh, they're so vital, they're so young. And yet the way you describe
these changes in the epigenome and the way you have
framed aging as a disease leads me to ask are periods
of i
mmense vitality, the same periods when we're aging faster. - Yes, yes. And this is something
I've never talked about, at least not publicly. So this is a really good question. So those chemicals we can measure, it's also known as the Horvath's clock. It's the biological clock, it's separate from your chronological age. So actually what I didn't mention is that when the AI looked
at the faces of those people, they could predict their
biological age, their internal age. So your skin represents the
age of your organs as well. And the people that look after themselves, we can talk about how to do that later. But there are some people
that are 10, 20 years younger than other people biologically and it turns out if you
measure that clock from birth or even before birth,
if you look at animals, there's a massive increase
in age, based on that clock, early in life. So you're right, so that's
a really important point, that you have accelerated aging during the first few years of life, and then
it goes linear
towards the rest of your life. But there's another interesting
thing that you brought up, which is that we're finding that the genes that get messed up, that get scratched that are leading to aging are those early developmental genes. They come on late in life
and just mess up the system and they seem to be
particularly susceptible to those scratches. So what's causing the scratches? Well, we know of a couple
of things in my lab, we figured out. One is broken chromosomes, DNA dama
ge, particularly cuts to the DNA breaks. So if you have an x-ray or a cosmic ray, or even if you go out in the sun and you'll get your broken chromosomes that accelerates the unwinding
of those beautiful DNA loops that I mentioned. We can actually do this to a mouse. We can accelerate that process
and we get an old mouse, 50% older, and it has
this bent spine kyphosis. it has gray hair, it's organs are old. So we now can control aging,
the forwards direction. The other thing that accelerates agi
ng is massive cell damage or stress. So we pinched nerves and we
saw that their aging process was accelerated as well. - Incredible, this is more
of an anecdotal phenomenon. It is an anecdotal phenomenon, but at this experience
of in junior high school, going home for a summer and you come back and then high school in the US usually starts eighth or ninth grade, or grade eight or grade
nine for you Canadians. And then some of the kids, like they grew beards over the summer, or they completely ma
tured
quickly over the summer. Do you think there's any reason to believe that rates of entry
into and through puberty can predict overall rates of aging? In other words, if a kid
is a slow burner, right? They basically acquire
the traits of puberty slowly over many years. Can we make some course prediction that they are going to live a long time versus a kid that goes home for the summer and comes back a completely
different organism or appearing to be a
completely different organism. Like they
basically age
very quickly in the summer. Does that mean they're
aging very quickly overall? - Well, yeah, I don't
want to scare anybody. - Sure. - That there are studies that show that the slower you take to
develop it also is predictive of having a longer, healthier life. And it may have something
to do with growth hormone. We know that growth hormone is pro-aging. Anyone who's taking growth
hormone, pay attention. - Just look at someone
who's taking growth hormone. - Yeah. - They often will
acquire these
characteristics of vitality, like improved a smoothness of skin, but their whole body shape changes often. - Yeah, I mean you'll feel better for a short amount of time. You'll build up muscle, you feel great, but it's like burning
your candle at both ends. Ultimately, if you want to live longer, you want less of that. And the animals that have been generated and mutants that have low growth hormone, or sometimes these are dwarfs,
they live the longest by far. A guy in my lab, Micha
el Bankowski, he had the longest lived mouse, a mouse typically lives
about two and a bit years. He had a mouse that lived five years and he gave it chloric
restriction, so fasting, combined with one of
these dwarf mutations, low growth hormone, I
think he called it Yoda. You look at who lives the longest, it's the really small people. This is a bit anecdotal, but it sounds like it might be true, is that the people who
played the munchkins in the Wizard of Oz, many
of them went on to live into t
heir nineties and beyond. - Really? - Yeah. - Huh, amazing. - And are there are some
Lauren dwarfs as well? There are dwarf mutations in South America and they seem to be protected against many of the diseases of aging. You barely ever see heart disease or cancer in these families. - So I having owned a
very large dog breed, a bulldog Mastiff who lived
a long life for a bulldog, 11 years, but there are
many dogs that will live 12, 16 years that are smaller dogs. Can we say that there's
a direct
relationship between body size and
longevity or duration of life? - Well, there is, but that
doesn't mean that you're a slave to your early epigenome
nor have to your genome. The good news is that
the epigenome can change. Those loops and structures can be modified by how you live your life. And so if you're born tall and I wasn't, and I wished at the time I did grow, but no matter what size you are, you can have a bigger impact on your life than anything your genes give you. 80% is epigenetic n
ot genetic. - So let's talk about some of
the things that people can do. And I've kind of batch
these into categories rather than just diving right
into actionable protocols. So the first one relates to
food, blood sugar, insulin. This is something I hear a lot about, that fasting is good for us, but rarely do I hear why it's good for us. One of the reasons I'm
excited to talk to you today is because I want to drill
into the details of this because I think
understanding the mechanism will allow
people to make better choices and not simply to just
decide whether or not they're going to fast or not fast, or how long they're going to fast, I think should be dictated
by someone understanding of the mechanism. So why is it that having
elevated blood sugar, glucose and insulin ages us more quickly and or why is it that having
periods of time each day or perhaps longer can extend our lifespan? - Well, let's start with what
I think was a big mistake was the idea that people
should never be hun
gry. We live in a world now where there's at least three meals a day, and then we've got companies
selling bars and snacks in between. So the feeling of hunger, some people never experienced
hunger in their whole lives. It's really, really bad for them. It was based, I believe
on the 20th century view that you don't want to
stress out the pancreas and you try to keep insulin
levels pretty steady and not have this fluctuation. What we actually found,
my colleagues and I, across this field of long
evity is that when you look
at first of all animals, whether it's a dog or a mouse or a monkey, the ones that live the
longest by far 30% longer and stay healthy are the ones
that don't eat all the time actually was first discovered back in the early 20th century,
but people ignored it. And then it was rediscovered in the 1930s, Claude McKay did Clark restriction. He put cellulose in the food of rats, so they couldn't get as many
calories even though they ate. And those rats lived 30% longer, bu
t then it went away
and then it came back in the 2000's in a big way, when a couple of things happened, one is that my lab and others showed that there were longevity
genes in the body that come on and protect
us from aging and disease. The group of genes that I
work on are called sirtuins there's seven of them. And we show it in 2005 in a science paper, that if you have low levels of insulin and another molecule called
insulin like growth factor, those low levels turn
on the longevity genes. On
e of them that's really
important is called SIRT1. But by having high levels
of insulin all day, being fed, means your longevity
genes are not switched on. So you're falling apart, your
epigenome, your information, that keeps your cells
functioning over time, just degrades quick. Your clock is ticking
faster by always being fed. Okay. The other thing that I
think might be happening by always having food around is that it's not allowing the
cell to have periods of rest and re-establish the epigen
ome. And so it also is accelerating
in that direction. There's plenty of other reasons as well, that are not as profound, such as having low levels
of glucose in your body will trigger your major
muscles in your brain to become more sensitive to insulin and suck the glucose
out of your bloodstream, which is very good. You don't want to have glucose
flowing around too much, and that will ward off type two diabetes. - So hunger of course is
associated with low blood glucose and low insulin. Do you
think there's anything about the subjective
experience of hunger itself that could be beneficial for longevity? - Yeah, I do, though you get used to
the feeling of not eating, so I'm kind of screwed that way. - It's like cold water,
you eventually adapt. - You get used to it, unfortunately, but there are some studies
that are being done at the National Institutes of Health that are able to simulate
the effect of hunger, but still provide the calories. And it's looking like
there's a small compo
nent that's due to hunger, but most of it, actually, is because
you've got these periods of not being fed and then the body turns on these defensive genes. There's a really interesting experiment that was published maybe
a couple of years ago by Rafael de Cabo down at the NIH. What he did was he took over 10,000 mice and gave them different combinations of fat, carbohydrate, protein. And he was trying to figure out what was the best combination. And then you also cleverly had a group. Well, two
groups, one
that was fed all the time or ate as much as they wanted and the other group was only
given food for an hour a day. And it turns out they ate roughly the same amount of calories, 'cause of course in an hour
they're stuffing their faces. It turns out it didn't matter
what diet he gave them, it was only the group that
ate within that window that lived longer and dramatically longer. So my conclusion is, and mice are very similar
to us, metabolically, I think that tells us that
it's not
as important, what you eat, it's when
you eat during the day. - What is the protocol that people can extrapolate from that? Or maybe I should just ask you, what is your protocol for when to eat and when to avoid food? Do you fast, do you ever
fast, longer than 24 hours? What do you do? And what do you think is
a good jumping off place if people want to explore
this as a protocol? - Well, if there's one thing I could say, I would say definitely
try to skip a meal a day, that's the best thing. - D
oes it matter which meal or they're essentially equivalent? - Well, as long as it's at the end or the beginning of the day, because then you add
that to the sleep period where you're hopefully not eating. - I think that that's an excellent point. I realized it's a simple one, but I think it's an excellent one 'cause I think one of
the things that people struggle with the most
is knowing when and how to initiate this so-called
intermittent and fasting. And the middle of the day
obviously is not t
acked to the sleep cycle in the same way. So it's much harder as
well for many people. - Yeah, well, I'll tell you what I do. I skip breakfast, I have a
tiny bit of yogurt or olive oil because the supplements I have
need to be dissolved in it. And then I go throughout the whole day, as I'm doing right now, here
with this glass of water here, I'm just keeping myself
filled with liquids. And so I don't feel hungry, be aware that the first
two to three weeks, when you try that you will feel hungry
and you also have a habit of wanting just to chew on something that there's a lot of
physical parts to it, but try to make it through
the first three weeks and do without breakfast
or do without dinner and you'll get through it. And I did that most for
most of my life, actually, mainly because I wasn't
hungry in the morning. Some people are very hungry in the morning and they may want to consider
skipping dinner instead, but I will go throughout the whole day. I don't get the crashes
of the high
glucose and the low glucose that anyone who goes, oh man, it's three O'clock,
I'm going to need a sleep. If you do what I do, you will not experience that anymore because what my body does is it regulates blood
sugar levels naturally. My liver is putting out
glucose when it needs to, and it's very steady
and gives me pure focus throughout the day. And I don't have to even
have to think about lunch, I'm just powering through. At dinner, I mean, I love
food as much as anybody. So I will eat a reg
ular,
pretty healthy meal. I'll try to eat mostly
vegetables, I can eat some fish, some shrimp, I rarely will eat a steak. In fact, my microbiome is
so adapted to my diet now, if I eat a steak, it will
not get digested very well. I'll feel terrible. - If I don't eat a steak, I feel terrible. [David laughs] - Argentine lineage, but
we can talk about that some other time. - Well, everybody's different,
that's the other thing. What works for me may
not be perfect for you and we do have to measure
t
hings to know what's working. I rarely eat dessert, I
gave up dessert and sugar when I turned 40 and occasionally I'll steal a bit of dessert 'cause it doesn't hurt
if you steal it, right.? But other than that I avoid sugar, which includes simple carbohydrates,
bread, I try to avoid, I've actually noticed,
this is just a side note. I used to get buildup
of plaque pretty easily and every time I went to the dentist, they'd have to scrape it off. And I even bought tools to scrape it off. 'cause it
was driving me nuts. I don't get pluck anymore and I think it's because of my diet. I don't have those sugars in my mouth that the bacteria feed on and then form the biofilm on the teeth. Much better breath, by the way. - That's a benefit. Should you ever fast longer than this. It sounds if you go to bed, well, you used to tend to stay up late. I know because I get texts from you at like two in the morning my time, which means you're out very
late and up early as well. But assuming that people g
o to sleep sometime around 1130 or
12, plus or minus an hour and wake up sometime around 7:00 AM plus or minus 90 minutes,
you're eating more or less on. It sounds something like
a 20 hours of fasting, four hours of eating
or 16 hours of fasting and eight hours of food intake, et cetera. But do you ever do longer fast, like 48 hours or 72
hours a week long, fast? - Occasionally I do. So my typical day I would only
eat within a two hour window. Just usually I'm either eating out or. - 'Cause you'
re 22 too. - Yeah, but I love well. - And if you exercise,
do you feel like you, then you just power through
and maintain that fasted state? - Absolutely, I can exercise and now I've already so used to it. I don't feel like I need food
after exercising, I used to. But have I gone longer? Yes, but not very often. I find it quite difficult
to go more than 24 hours. But when I do it, maybe it's once a month, I'll go for two days after
two and actually even better, if you go for three days without e
ating, it kicks in even greater
longevity benefits. So there's a system called
the autophagy system, which digests old and
misfolded proteins in the body. And there's a natural cleansing that happens when you're hungry. Macroautophagy its name is
but a good friend of mine, Ana Maria Cuervo at Albert
Einstein College of Medicine discovered a deep cleanse called the chaperone mediated autophagy, which kicks in day two, day three, which really gets rid
of the deep proteins. And what excites me is y
ou
just put out a big paper that said, if you trigger
this process in an old mouse, it lives 35% longer. - [Andrew] Wow. - Yeah, so it's a big deal. If I could go longer, I would. But I just find that with my lifestyle and I'm going always
day, 110% I need to eat at least once a day unfortunately. - One more practical question
then a mechanistic question related to this, the practical question is when you are fasting,
regardless of how long, I know you're ingesting fluids like water and presumab
ly some caffeine
I heard you had several or more espresso today,
which is impressive, but are you also ingesting electrolytes? Like I know some people get lightheaded, they start to feel shaky when they fast. And that the addition
of sodium to their water or potassium magnesium is something that's becoming a little more invoke now. Is that something that you do or that you see a need for people to do? - Well, it makes sense, but I
haven't had a need to do it. So I don't, I drink tea
during the d
ay and coffee when I'm first awake and
I don't get the shakes. So I don't fix what's not broken. And I do add things to my protocol that I think will improve
me and avoid those things of course that wont. But yeah, because I
don't have a need for it, I don't try it. But it does make sense, especially if you've had a
big night the night before, you'd probably want to
supplement with that. But I think there's fair
amount of good stuff in tea and coffee as it is. - Okay, so then the
mechanistic que
stion is, you've told us that there's ample evidence that keeping your blood sugar
low for a period of time is 24 hours, can help
trigger some of these pro longevity anti-aging mechanisms. And that extending them
out two or three days can trigger yet additional
mechanisms of gobbling up of dead cells and things of that sort. How is it that blood glucose
triggers these mechanisms? Because we've said, okay, remove glucose and things get better. You've talked before maybe
we could talk more now abo
ut some of the underlying
cellar and genetic mechanisms, things like this are sirtuins, but how our glucose in the sirtuins actually tethered to one
another mechanistically. - There's a really good question, that proves you're a scientist
or a world-leading one. So what we've now know is
that these longevity pathways, we call them these longevity
genes, talk to each other. And we used to say, oh, my longevity genes is
more important than yours. It was ridiculous. 'Cause they're all talking to ea
ch other, you pull one lever and
the other one moves. And the way to think of it is
that there are systems set up to detect what you're eating. So the sirtuins will mainly
respond to sugar and insulin. And then there's this
other system called mTOR, which is sensing how much
protein or amino acids are coming into your body. And they talk to each other, we can pull one and affect
the other and vice versa. But together when you're fasting, you'll get the sirtuin
activation, which is good for you.
And you'll also through
lack of amino acids, particularly three of them,
leucine, lysine and valine. The body will down-regulate
mTOR and it's that up sirtuin, down MTOR that is hugely beneficial and turns on all of the body's defenses, the pro chewing up the old proteins, improving insulin sensitivity,
giving us more energy, repairing cells, all of that. And so these two pathways, I think, are the most important for longevity. - So interesting, you mentioned leucine, within the resistance train
ing
slash body building slash fitness community. Leucine gets a lot of attention because there are long-standing debates about how much protein one needs per day and how much you want and
can assimilate at each meal. It makes for many YouTube videos
and not much else, frankly. However, it's clear that
because of leucine's effects on the mTOR pathway, that
there are many people, not just people in these
particular fitness communities that are actively trying
to ingest more leucine on a regular ba
sis in order
to maximize their wellness and fitness and in some
cases muscle growth but also just wellness. But what I interpret your
last statement to mean is that leucine, because
it triggers seller growth is actually pro aging in
some sense, is that right? - Well, it could be that's
what the evidence suggests. And again it goes back to the debate. Should you supplement with
growth hormone or testosterone? All of these activities will
give you immediate benefits. You'll bulk up more. You'll fe
el better immediately, but based on the research, it's at the expense of long-term health. So my view of longevity, the way I treat my body is
I don't burn both candles. I have one end of the candle lit, I'm very careful I don't blow on it, but I also do enough exercise that I'm building up my
muscle, but I'm not huge. Anyone who's seen me, knows that I'm not a
professional bodybuilder, but I tried to actually, here's the key. And I haven't said this
publicly, that I can remember. I pulse things
so that
I get periods of fasting and then I eat, then I take a supplement, then I fast, then I exercise and I'm taking the supplements and eating in the right timing to allow me to build up muscle sometimes because you can't just expect
to take something constantly and do something
constantly for it to work. And that's why it's
taken me about 15 years to develop my protocol. And there's a lot of subtlety to it. - Yeah, it sounds like a
very rational protocol. Does the name Ori Hofmekler
mean an
ything to you? - No. - Okay, just briefly, I
discovered Ori Hofmekler about 15 years ago, he was
a in Israeli special forces. He's now got to be close to 70. Forgive me Ori, if that
number is inflated. He wrote a book called 'The Warrior Diet', which got very little
attention at the time. But what he said was when he
was in Israeli special forces, they rarely ate more than once per day. And sometimes once every
second or third day. And this is a guy who maintains incredible physical stature,
he'
s very lean, very strong and very vital at, I
wouldn't say an advanced age, but he's getting up there and he just seems to be
getting better and better. Ori Hofmekler was the person
who essentially founded, if you will, although
our ancestors founded, to be completely fair, the so-called intermittent fasting diet. He called it the warrior diet and this book didn't get much attention. But one of the things that you just said really reminded me of Ori. I sat down with him, I
actually went to his h
ome and sat down with him and he
said, fasting is wonderful but these pulses where
you nourish the body or even slightly over nourish the body provided they aren't too frequent, have a tremendous effect on vitality. And so I want to use
that as kind of a segue to address this issue of
vitality versus longevity, because here you're telling me and certainly the evidence supports that growth hormone will make
you feel better and younger taking testosterone or estrogen,
we should probably say. There
are women who take
hormone therapies later in life who take estrogen, they experience a strong
increase in vitality if it's done correctly, but
there is an effect of aging, the body more rapidly, it's sort of a second puberty if you will, but this idea of restriction
and then pulsing, not necessarily feast and famine, but certainly famine and
feast in lowercase letters, there really seems to
be something about that. So at a cellular level, we'd kind of go back to
mTOR and the sirtuins. How do y
ou think that the
cells might be reacting to this kind of lowercased
feast and upper case famine type protocol? - Right, well, the pulsing, I
think is what you want to do is to get the cells to
be perceiving adversity. Okay, 'cause our modern
life we're sitting around, we're eating too much,
we're not exercising. Our cells respond. They go, hey, everything's
cool, no problem. And they become relaxed and their own turn on their defenses and we age rapidly. We can see it in the clock. People who e
xercise and eat less, have a slower ticking clock, it's a fact. But my protocol is
different than most people's because I am pulsing it. Now, first of all, let's get to, why did I even think
that might be possible? 'Cause I didn't read the warrior diet. What I found in my research was that if we gave resveratrol on
this red wine molecule, that became well known in the 2000's. If we gave it to mice,
their whole lifespan, they were protected
against a high-fat diet, which we call the Western diet.
They had lean organs. They live slightly longer, but not a lot. And if we gave them a high-fat
diet without resveratrol, they actually lived a lot shorter. So it resveratrol protected
them against the high-fat diet. We gave it to them on a normal diet, they just ate it when they wanted, and there wasn't much effect. This is what's not known though it's in a supplemental data of the paper that nobody ever reads. The mice that were given
resveratrol every second day on a normal diet live dramatic
ally longer than any other group. - [Andrew] Interesting. - So people out there, my
critics say, resveratrol didn't extend the lifespan
of mice on a normal diet. Therefore it's not aging, it's just protecting
against a high-fat diet. Well, look at the
supplemental data, please. If you give it to the
mice every other day, we had mice living over three years. - Wow, that's a long time,
I have got many, many mice in my owner ownership
at my lab at Stanford and that's a very long life for a mouse. -
It was, by far. And so it was a long life span extension. And what that told me is that probably, you don't want to be taking
a supplement every day. You can take it either every other day or give your body a rest. And I do the same with my meals, I rest during the day and then
I give a nutritious dinner to my body and then give it
a rest, same with exercise. And then I try to time it
because there are times when I'm taking the drug
Metformin, which mimics low energy. For those of you who don't
know, Metformin is a drug given
to type two diabetics to bring down their blood sugar levels. But it's been found that
looking at tens of thousands of veterans and all those, that those two type two diabetics live longer than people that don't even get type two diabetes. So it's a longevity drug, right now you have to get it
from your doctor in the US, in most of the countries
you can just get it over the counter and you protected. It looks like, based on
epidemiological data, cancer, heart dis
ease for LT. What else? Dementia. So I take Metformin. - In addition, you take Metformin end
fast fasting each day. So when do you take it
relative to the fasting? - Yeah, I always take
Metformin in the morning, along with the resveratrol,
because for a number of reasons, but mainly because my body responds better and I've been measuring
my body for 12, 13 years. But here's the thing, if I'm
going to exercise that day, I will skip the Metformin. And a lot of people who do pay attention to this k
ind of thing, think that they should
stop taking Metformin 'cause they're never going to get muscle, or it's going to affect their
ability to build up muscle. But that's not true, what
Metformin does to you, it actually just reduces
your ability to have stamina because it's inhibiting your
body's ability to make energy. And so what happens is
when you're on Metformin, you do fewer reps. But guess what? Those muscles that you
do build up on Metformin, have the same strength and
have much lower in
flammation and other markers of aging. You just won't have that
extra 5% size of muscles. So if you want large muscles, don't take Metformin and you'll be fine during your exercise. But for me, I'm not trying to get giant. I want strong muscles
and I want to live longer and healthier. So I just try to time it
so that I get the most reps out of my exercise regime, but sometimes in scientific literature, it's worth bringing this up. If there's a 5% difference in a graph, then either the press rele
ase
or some reporter will say, oh my goodness, big difference, 5% contact Metformin during exercise. That's the headline. And then you go in and
it's barely significant. And the graph is distorted
because they've changed the axes to make it look bigger. And now it's become a myth that Metformin greatly inhibits
our ability to exercise, which is not true, but in
an abundance of caution, I skipped my Metformin on
days I'm going exercise. And not only that, I'm one of the 20% of people that has a s
tomach sensitivity to it. So if I'm not feeling great that day, I don't take it either. - You mentioned Metformin is available only by prescription from a
doctor, at least in the US. Berberine is a substance
that comes from Tree Barco. I also learned about
many years ago from Ori. He said, if ever, I'm going to overeat like a Thanksgiving meal or something, I take berberine, those were his words. And I tried it and what's
remarkable about berberine is that you can eat
enormous quantities of food
and not feel as if you've eaten
enormous quantities of food. I'm not necessarily
recommending people do this. But what I noticed was
if I took berberine, which my understanding is
it works very similarly to Metformin where some
of the AMPK pathway and the mTOR pathway, et cetera, that if I didn't ingest food
in particular carbohydrates, I would feel a little dizzy
and kind of get a headache, like almost hypoglycemic. What are your thoughts on berberine as an alternative to Metformin? And are th
ere any cautionary notes? Obviously people should
talk to their doctor before adding or subtracting
anything from their life, including breath order,
anything that comes up, but with all of that set aside, what are your thoughts about berberine and timing of low blood sugar
and these sorts of things? - Right, well, before I
had access to Metformin, I was taking berberine. It's often known as the
poor man's Metformin. - He just called me poor. - Women can take it too. So the thing with berberine
and we started it in my lab, it is effective at boosting
energetics in the body, just like AMPK and Metformin does. And we've actually given
it to rats and mice and seen that they are very healthy, especially on a high-fat diet. So I think it's likely to be good. There are some human studies that exist, clinical trials showing that it increases insulin sensitivity. You have to take high doses. - Which is a good thing, right? I think when people hear
insulin sensitivity, sometimes people think,
o
h, well that's bad, right? No, but you want your cells
to be insulin sensitive. You don't want a lot of
blood sugar floating around that can't be sequestered into cells. - Exactly, so this is
anti type two diabetes. And so that this berberine
does have wonderful effects on the metabolism of animals
and in some clinical trials on dozens of people that's being tested. Now, there's one cautionary
tale, which just came up, Caenorhabditis lab
published that berberine reduced the lifespan of worms, bu
t I'm not sure worms
trump human clinical trials at this point. - Not in my opinion, no disrespect to my C. elegans colleagues or rather my colleagues that work on C. - Yeah, well, what I like to do is to give all the information, people can decide what they want, but I would say based on the worm data, I wouldn't panic just yet. And I think berberine has been shown to be really safe in humans. - You mentioned resveratrol, think now would be a great time
to talk a little bit about, protocols for
resveratrol,
great seed extract, et cetera. Let's start with the obvious
one that I know you get a lot, but for the record, can't
I just drink red wine and get enough resveratrol, David. - You can try, you need to
drink about 200 glasses a day. - I'm sure it's been tried. - There are some, and I drink
a glass of red wine a day if I get the chance,
but any more than that, it's a lot of calories and
your liver will get fatty and it's all bad. So, I mean, realistically, you can only get the thousa
nd milligrams that I take a day from a
supplement that's pure. Now there are a lot of
people selling resveratrol. If it's not light gray or
white in color, throw it away. The brown stuff has gone
bad or is contaminated. And the contaminated stuff
beware it'll cause diarrhea. But regular resveratrol
should not do that. - So a thousand milligrams
per day is what you do. - Yeah and I had for about 15 years now. And you ingest that with
some fatty substance, like olive oil or yogurt, is that right?
- Yeah, you have to, and other supplements of course it's in curcumin. These are crunchy things, that is not going to get through your gut. And I'm not just making this up. I always base my statements
on human studies. So we've done a lot of
studies on resveratrol as have others since,
and we know that from, we found out early, I was
one of the first people to take a high dose for resveratrol. And when we included it with food, the levels in my blood went up five fold. And so you want to have
so
mething in there. If you just drink it with water, it's not going to get through. And unfortunately, some people
have done clinical trials without even thinking that they might need to dissolve it in something. - So are you taking this
all at once in the morning and chasing it with some olive oil or are you dissolving it in yogurt? What's the specific protocol? - Yeah, I've been improving perfecting what I do for about 10 years I would take some Greek yogurt, a couple of spoonfuls, put
the resve
ratrol on there, mix it around, make sure it's dissolved and put that in my mouth and swallow that, these days, what I like to do, because I've realized that olive oil and particularly oleic acid,
one of the mono unsaturated, fatty acids is also an activator
of the sirtuin defenses. So I'm trying to ingest
more of oleic acid. So I switched to olive oil. What I do is I put a couple
of teaspoons of olive oil in a glass mix around the resveratrol, and maybe some Coresatin
a similar molecule. Make s
ure it's dissolved. I put a little bit of vinegar and if I have a basil
leaf, I'll put that in. And it's like drinking
some salad dressing. And it's very- - Delicious, that raises a
question that I want to ask before we get to NMN
and NR and vitamin B3, which is by doing that, do you think that it breaks your fast? And I want to just frame this
question of breaking the fast in a more general scientific theme. And I'd love your thoughts on this. One of the questions I
get asked all the time is do
es ingesting blank break the fast, does eating this or drinking this, coffee? If I walk in the room and
someone else is eating a cracker, does it break my fast? People get pretty extreme with this, my sense and please tell me if I'm wrong, but my sense is that it
depends on the context of what you did the night before, whether or not you're
diabetic, lots of things. So for instance, if I eat an
enormous meal at midnight, go to sleep, wake up at 6:00 AM. I could imagine that black coffee or coffe
e with a little bit
of cream might quote unquote, break my fast, but the body doesn't have a breaking the fast switch. The body only speaks in the
language of glucose, AMPK, mTOR, et cetera. So do you worry that
ingesting these calories is going to quote unquote break your fast? And more generally, how do you think about the
issue of whether or not you're fasting enough to
get these positive effects? Because not everybody can manage
on just water or just tea, or we should say not
everybody is wi
lling to manage on just water or just tea for
a certain part of the day. - Well, my first answer is not scientific, it's philosophical. If you don't enjoy life, what's the point. And so I'd like a cup of
coffee in the morning, a little bit of milk, spoonful of yogurt, it's not going to kill me. Olive oil doesn't have protein
or carbs in it, not many. And so I'm probably not affecting those longevity pathways
negatively, but without that, first of all, I wouldn't
enjoy my life as much. Second, we
ll, the olive
oil isn't is not as great as the yogurt, but I'm trying to optimize and there's no perfect
solution to what we're doing. And we're still learning. We don't know what's optimal for me, let alone everybody else. But I'm with you, I don't believe that taking a couple of spoonfuls of something, unless it's high fructose corn
syrup is going to hurt you because I've now got the rest of the day till about eight, 9:00 PM
of not eating anything. And that I forgive myself for that. And that
there's a really good point here. You and I were discussing this earlier. The point about doing this is
that you try to do your best. If you go from regular living
to donate the whole day, you're going to fail. It's like quitting smoking, cold turkey. It's easy to chew gum
and stick the patch on because your body has to get
used to all sorts of habits. And it's social, it's physical,
putting stuff in your mouth, chewing, not just the
low blood sugar levels and your brain will fight it. Your limb
ic system is going to go, hey, do it, do it, do it. And you're going to have to fight it but once you get through
it, you'll be better, but you do it in stages. Do breakfast first, then do small lunch and then eventually cut lunch out. Don't go cold turkey
because everyone knows. It's a fact that if you
try to do a strict diet right out of the gates,
they'll almost always fail. - Now, I think that captures the essence of the fasting rationally
and irrational approach to supplementation very well
, along the lines of supplementation. What about NMN, NR and B3, niacin? How does one, I want to know what you do. I also want to know what I should do, and I think most people want
to know what they should do. These are molecules that
impact the sirtuin pathway impact the pathways that control aging or rates of aging in the epigenome. How do they do that? And how does one incorporate that into a supplementation protocol? Should they choose to do that? All right. - Well, disclaimer is I
don't re
commend anything, but I talk about what I do. So a bit of scientific background, these are two in genes that we discovered first in yeast cells when I was at MIT and then in animals as I
moved to Harvard in the 2000's one of my first post-docs, actually literally my
first postdoc Haim Cohen, published a great paper
just a couple of months ago and found that turning
on the sirtuin six gene, middle of the seven, number
six gene is very potent. It extended the lifespan
dramatically of mice that he
engineered both males
and females, which is great. So what you want to do
is so naturally boost the activity of these sirtuins. They are genes, but
they also make proteins. That's what genes
typically make or encode. And then those proteins
take care of the body in many different ways as we've discussed. So how do you turn on these
genes and make the proteins they make even more active? You want to rev up that system. So exercise will do
it, fasting will do it. What about supplementation? Well,
the first activator of
the sirtuins that we discovered that acts on the enzyme
to make it do a better job of cleaning up the body
and protecting resveratrol We looked at thousands
of different molecules, eventually tens of thousands. And the one that was the best
was resveratrol in the dish. And then we gave it to
little organisms, worms, and then flies and
mice, eventually humans. And we saw that it activated that enzyme. So resveratrol is one way to activate it. And you can think of it as the
accelerator pedal on a car. It revs it up, but there's
something else that the sirtuins need to work and that's NAD
and is a really small molecule, little chemical in the
body that we need for life. It's used by the body
for chemical reactions, for a hundred different
reactions in the body. And without it, you're dead
within seconds, you need NAD. The problem that we've
seen is that NAD levels decline as you become
obese, as you get older, if you don't ever get hungry and the body not only doesn
't make enough of it, it's chewing it up as well. There's an enzyme called
CD38 that Eric Verdin over at UCSF showed choose up. Now he's now at the Buck
Institute in California, choose up NAD as you get older. So it's a double whammy. You don't make as much and chew it up, which is really bad because
what we've shown in my lab and so have others is that NAD levels are really important for keeping
those sirtuins and defenses at a useful level. And you can give a lot of resveratrol but if you don'
t have the fuel, you're basically accelerating a car that doesn't have enough gas. So you want to do both. And that's what I do. I take a precursor to NAD called
NMN and the body uses that to make the NAD molecule in one step. And so I know from measuring
dozens of human beings, that if you take NMN for
the time period that I do, I've been taking it for years. But if you take it for about two weeks, you'll double on average, double your NAD levels in the blood. Okay, that's not public informatio
n. That's from clinical trials
that are not yet published over the last two years. There are other ways
to increase NAD levels in someone like me, who's
getting older, I'm 52 now. You can take NR, which
is used to make an amend, which is used to make
NAD, and both NMN and NR are sold by companies in the US. NR is laxter phosphate, the phosphate is a small
chemical the body needs. You've probably heard
of the atom, phosphorus. Let's go back one step. How do you make NR? NR gets made from vitamin
B3, often. You can also find it in
milk and other foods, but sometimes people ask me, why don't you just take vitamin B3? And won't that just force
the body to make NAD? And the answer is no, it
doesn't work very well. We know this just by doing the experiment, but the reason I think is is that NAD, I said, it's a small molecule, but relative to vitamin B3, it's big. It's got those phosphates
on there, it's got a sugar, it's got the vitamin B attached. So you've got all these
components that com
e together to make this very complicated
little molecule called NAD. When you give NMN, it
contains all three components that the body needs to make NAD. If you give NR or just vitamin B3, which is an even smaller molecule, the body has to find
these other components from somewhere else. So where do you get phosphate, well, the body needs it for
DNA, it needs it for bones. So high doses of something that requires additional phosphate makes me a little concerned. And we have compared to
NMN and N
R head-to-head in mouse studies, for instance in NMN, we've shown in a cell
paper a few years ago, makes mice run further, old
mice can run 50% further 'cause they had better
blood flow, better energy. NR are at the same dose, did not do that. In fact, it had no effect. - I see, dosage wise, if
I were elect to take NMN in supplement form to
increase my NAD levels and presumably slow my aging, how much NMN should I take? What's the protocol that you do? And are the various
forms that are out ther
e, are some better or some worse? - Well, I'm always happy
to tell you what I do and what my father does,
my 82-year-old father, we take a gram of NMN every day. - So it's a gram resveratrol
and a gram of NMN. - Right. - Okay a thousand milligrams. - Now another important point, which is, I'm not the
same as everybody else. I have a different
microbiome, age, sex, right? And so I've been measuring myself and so I know if something's, or I think I know if
something's making me better or worse bas
ed on measuring
45 different things. So I just want people to be aware that what I do may not perfectly
or work at all for others, but I have studied, as I said, dozens of people who take NMN, at a gram, sometimes two grams. And I know by looking at all those people that without any exceptions,
that if you do what I do, your NAD levels go up by
about two fold or more. And so I do that every day,
the thousand milligrams. Now people sell it. Now I never get into brands and all that. First of all,
I don't have
the time to measure products. I don't know, though I should say, I do want to say I'm working on a solution for people to know what works and what's real and what
isn't, but I'm not there yet. And in the meantime, I would say, if you do want to buy this,
let's say you want to buy NMN, look for a company that
is well-established that has high levels of quality control. Look for three letters, GMP, which is good manufacturing practices. And so that means they make
it under a certain l
evel of quality control. You're not going to find
iron filings in there and it probably has the stuff
in it that they say it does. But so that's all I can say right now. I'm working on something that's
going to be much more helpful, but overall, make sure it's
white, crystalline NMN, and that to me, it tastes
like burnt popcorn. - You crack open the capsules, and you'll take a little sample to make sure it tastes like burnt popcorn. - Well, when I'm making
my capsules, I'll taste it and I do a l
ot of quality
control on the stuff that I take. - Do you take that gram all at once with the resveratrol or do you take it spread
throughout the day? - It's all in the
morning for those things. So if I take Metformin, it's NMN and the resveratrol altogether. And there's a good reason for that. It's all scientific, I try to be. The levels of NAD go up in the morning in our bodies naturally. Our bodies actually have a
cycle of NAD, it's not steady. - It's Arcadian? - It's Acadian. In fact, NAD con
trols your clock. This was shown by Shin Imai and colleagues in this nice science
paper about a decade ago, that if you disrupt the NAD cycle, which is controlled by the
sirtuin gene that we worked on, that is what's telling your
body, oh, it's time to eat, it's time to go to sleep. And if you take these, the NMN
late at night, for example, you can disrupt your circadian rhythms. - Interesting. - Conversely, when I travel
and I want to reset my clock to the time zone, I will take
a boost of NMN
in the morning and I feel great. - Does this protocol for you, does it produce any immediate effects of increased energy, et cetera? You mentioned that one would,
if it's right for them, would have to take it
for at least two weeks to start to see the NAD levels increase. At that point, when NAD levels increase, could one possibly expect an increase in overall energy, focus, et cetera? I realize we're not making promises here, but I'm just wondering whether
or not the only measure of whether or
not this protocol is working is whether or not you die at
age blank or blank plus 20. And of course, once you're dead, you can't really know if
you would've lived longer if you'd done something
differently and vice versa. - Sure, well, there was a
study again by Shin Imai my good friend at Washington
University in St. Louis that showed that improves, remember this insulin sensitivity,
which is a good thing. But you can't know your
insulin sensitivity unless you're measuring glucose, have a gluco
se monitor on your arm. - Do you have one on right now? - No, no, I used to, I learned a lot. - Yeah, last time I
saw you had this thing, it looks like a small leach, not a large leach and it was
measuring your blood glucose. - They're very informative
because you learn what your body reacts to
and grapes were really bad. Rhonda Patrick agrees with
that, but the issue was, was what, where were we, Andrew? - The issue is whether
or not you can expect any immediate effects on
energy, vitality, foc
us, just even subject. - So what do you feel, is the question. And anecdotally, 'cause I've been taking
this for a long time, if I don't take it, I
start to feel 50 years old, it's horrible. I can't think straight. It may be placebo, but who knows? But what we're doing now are
very careful clinical trials. We've done the safety for two years, and we're now treating elderly patients at Harvard Medical School with
some wonderful colleagues. And those people are actually going to be an currently in
MRIs. So you can measure the
energetics and the NAD levels in their legs as they
exercise in real time. And that will tell us if
what we see in the mice is increased endurance actually works. In the meantime, it's fun
to talk about anecdotes. I have a number of athlete friends, some of which have increased their load, their time in marathons, for example. There's a good friend
of ours in our circle that is winning marathons at age 50 now. And he attributes that to
the protocol that he's on. - I
nteresting, I haven't
started taking NMN, but I'm planning to do that
when my next birthday arrives, which is in a couple months. But I do experiments on my
sister and have for years, I have a sister who's three
years older than I am, who is very enthusiastic
about these protocols. And I'll tell you that
after reading your book, I started purchasing
for her and giving her an NMN supplement and she
claims and I believe her. She has a quite sensitive system and she's very tuned into it. She feels
far and away
better when she takes it, as opposed to when she doesn't and I've done the control
experiment of removing her supply, and then giving it back to
her in this kind of thing. So that's my other laboratory. This is what younger brothers
do to their older sisters. I have a question about something that if it has no relevance, we can just treat it as a speed
bump and then move right on. And the artificial sweeteners, these things that we
should say non-glucose, increasing sweetener. So yo
u've got Stevia,
which is a plant basically. And then you've got
sucralose and aspartame and all these things. There is some evidence that
I know we're both aware of, they've been publishing
quite reputable journals, showing that they can
disrupt the gut microbiome in certain cases in particular saccharin, the one that basically
nobody uses anymore. And it's questionable as
to whether or not Stevia has the same negative effects, et cetera. That's not what this is about, but in terms of the sensa
tion of, or the perception of sweet taste, is that itself a possible detriment to these pro-longevity,
forgive me for using the term, the pathways. If I were to drink a
diet coke during a fast, am I somehow disrupting this? And I'm asking this question, because I get asked this question a lot. - Well, there may be small effects. I don't think they're
worth worrying about. Joe Rogan laughed at me 'cause
I was drinking a diet coke during the first
interview I did with them. I will drink diet coke,
I've
read the scientific literature. And again, it's this 5% thing that I think is blowing out of proportion. If I was to put a number
on it, I would say, if eating a high sugary meal or drinking a sugar-filled soda, what is that, 30 grams of sugar? Let's say that's a 10
out of 10 bad for you. A diet coke might be a one. And if I'm, which am I going to do? I could have a 10 or a one
or go without in my life. I'll do the one on occasion. I try to avoid them because I
don't like the ones as much.
But you can't say that sucralose is equivalent to drinking a sugary soda. There's just no comparison. And I think suc, what is it? Stevia, I do use Stevia whenever I can, because it's a naturally sourced product. And I haven't seen any good evidence yet that it's bad for you. But I think a lot of this is overblown, and a lot of it's the media trying to give equal weight to stories
as you know as a scientist. It can be frustrating
when something's a 10 and something's a one,
and they're equated.
- How do I say this respectfully? I think if science
journalists were required to post their credentials
alongside their name, [chuckles] then people would take the articles into, with additional grain of salt, right? I mean, in other words, that I think that the science media is mainly generated
around two specific goals. One is to make people very, very afraid or get people very, very excited, and oftentimes the get people excited part is sponsored content, and I think that's overlooked in an
y case. Thank you for that. I want to talk about iron and iron load. We were talking earlier about ferritin. And of course, women menstruate. And so their iron needs
are greater than people, men that don't menstruate or women that don't menstruate. I don't think we can get right down into how much iron somebody needs because it'll vary person to person. But I was surprised to learn that iron is actually going to accelerate the aging process in various contexts. - Well, this is a new
finding out
of Spain. Manuel Serrano's lab has
found that excess iron will increase the number of
senescent cells in the body. And senescent cells are these zombie cells that accumulate as you get
older and they sit there and they cause inflammation mainly and also can cause cancer. And it's found that if
you get rid of these cells or never accumulate
them, you stay younger. In animals, and there's some
really interesting studies out of Mayo Clinic in humans as well. So iron is a pro-senescent metal. And so
what I think is that if you're taking
excess iron as a supplement, you're probably accelerating
your aging process. The other thing that I
found really interesting is I've looked at hundreds of thousands of people's metabolism and
their blood biomarkers. I was one of the first people in InsideTracker as a board member, and I'm still their scientific lead guy. So I can look anonymously at hundreds of thousands
of people's blood work. And we also know how fit
they are, how old they are. Some of t
hem are marathon runners, some of them are CrossFit. And there's a signature of health that actually is different
than your average person. Now, I'm not going to
say bad things about MDs 'cause a lot of my best friends are MDs and I work with them at
Harvard Medical School. The issue though, is
that with MD training, there's a scale of what's normal, and if you're out of that normal range, something must be wrong, that's the paradigm that they work under. But first of all, everybody's different,
and you want to know their baseline and track people over years to
know what's normal for them. And what I find for example, is people who are really
healthy and live the way I do and have a diet that's fairly
vegetarian, but not strict, still have slightly low hemoglobin levels, slightly low iron, slightly low ferritin, but we have super amounts
of energy, we're not anemic. And we're getting along great in life. But a doctor who just
looks at that might say, oh, we need to give you more iron.
All right, so what I'm
getting at is an example of, we need to personalize medicine and look at people over the long run to know what works for them
and what's healthy for them, and not just work towards
the average human, but work towards what's optimal for human. - I love that answer. You mentioned tracking
and tracking over time. And this is a really interesting area that I know you have been
focused on for a long time. I've been getting blood worked
on about every six months frankly, since I
was in college. I just got, I like data and I got interested in
supplementation and exercise 'cause it made me feel better, but I also want to know what
was going on under the hood. So you get numbers back, you
get this hormone, that hormone, this blood glucose measure, et cetera. How do you make sense of the data? I mean, what InsideTracker is doing aside, how do you personally
make sense of the data in ways that might differ from the way that a standard MD might
look at one of these charts? B
ecause the standard practice is to say, is it red, yellow, or green, right? Is it basically too high or too low? Is it somewhere close to
the margins or are you okay? Are you in these ranges? Are there any things
that you pay attention to that you think are
particularly interesting for people to just take note of? I mean, we're not asking you to go against anybody's physician. But what sorts of things
should people start to educate themselves about in terms of what these
molecules are on their c
harts if they choose to get them,
and what do you look at? - Yeah, well, there's a lot there. The first is that you
should be tracking things, because one measurement isn't enough. These things vary and over time. And if you can have a
decade or more of data, it's super important, informative, as you know, well know, as you know. So the physician, interestingly, my physician, let's
take him as an example. So he sees me, he says,
"How are you feeling?" "I'm feeling great." "Okay, see you next
yea
r," that's craziness. Anyway, so I say, okay, stop. Let's talk a little bit about. - Let me educate you, that's
what David tells his physician. I imagine that the
12-year-old David Sinclair says to a physician, "Listen, let's have a
different discussion." Is that how it works?
- It is. He finds me pretty annoying
as does my dentist. But so I say, so hang
on, I've got this data. I've got the InsideTracker data. So I pull that up on the screen, and I'm showing him the
changes in my cholesterol and
my CRP, which is
inflammatory marker as you know. And we're going through it, and you can see things change over time, and I've corrected them as they go slightly out of
the optimal range for me, which is different than
what he would do, of course. But what was funny is that he says, this is great, I love this data. But I'm not allowed to get
this because of course, the insurance companies won't pay for it. So again, you can pay out of pocket. It's not super expensive. I would say, if you save
a
bit of money on a coffee, you can afford this kind of stuff. But the main point is that
doctors do like this data. It's just that they're
unable to spend the money on every one of their patients to get it. - Is there a code word that someone can use with their physician that will trigger a
comprehensive blood test? I keep trying to figure
out what's the code that one needs to ask
or tell their doctor, I'm feeling blank so that
they get a full blood panel. - Well. - Do you have to be hemorrhagi
ng
from the gut or something? - Well, I usually use the WTH method, which is what the hell? And then he says, "Okay, we'll do it." - 'Cause I think a lot of
people out there are thinking, look, I'd love to have blood
work repeatedly over time, but that's hard to get
for financial reasons, but also a lot of people
just don't know how to approach the conversation. And this is one of the things that I hope that we can educate people on, that they deserve to know what's
going on inside their body, a
nd that it makes a
doctor's visit worthwhile, and that you don't have to
feign illness in order to do it. - Right, yeah, and a lot of people do. So I would say, if you
can't afford these tests, there are increasing number of companies that offer these tests,
InsideTracker is one of them. And you just do it a couple
of times a year at a minimum. And then you can share
that with your doctor. If you can't afford that, then
I would say to your doctor, here are the main ones
that Andrew and David do.
- Yep, and we must. And there's an email that is something like 555, or a phone number, rather, it's 555-5555. I think if they have any complaints, they can just call that number. David will pick up on the
east coast business hours and I'll pick up outside of those hours. - But there was the
main ones, I would say. Your blood sugar levels,
you want to do your HbA1c, which is your average glucose
levels over the month. There's CRP, which I
mentioned for inflammation. - Yeah, let's talk about
C-r
eactive protein for a second. 'Cause I think it's been shown to be an early marker
of macular degeneration of heart disease, of a
variety of different things. CRP is something that we don't hear enough about, I think. Maybe, what do you know
about CRP that I don't, I'm guessing a lot, but. - Oh, it was originally picked up as something that was
associated with heart disease in the Framingham study, I believe. It is the best marker for
cardiovascular inflammation and is also, we use it as
a predi
ctor of longevity, and its levels go up with mortality. And so this is an association, but there's enough data that I would say, if you have high levels of CRP, you need to get your levels down quickly. And the levels usually go up with age and with levels of inflammation. So the ways to get it down
would be to switch the diet, eat less, try to eat more vegetables. You'll find it will come down, and there are also drugs that can do it. Anti-inflammatories can do it as well. But CRP is, it's actu
ally, hCRP, there's a high sensitive
hCRP, your doctor will know. Get one of those readings. 'Cause if you've got
normal blood sugar levels, your doctor, or fasting
blood sugar levels, your doctor might say you're fine. But a lot of people
have normal blood sugar, but have high CRP, which is
just as bad for you longterm, and can predict a future heart attack. - On the lines of heart attack. I want your thoughts on cholesterol and serum cholesterol
and dietary cholesterol. I cannot, for the life
of me, get my arms around this literature. And even if I ignore all
the essentially nonsense that's out there in various
social media groups, as saying cholesterol is the
worst thing in the world, or cholesterol is not, or dietary cholesterol has nothing to do with serum cholesterol and
nothing to do with longevity. I can't seem to sort
through the very basic data that essentially ask, is having high levels of LDL
going to kill me earlier? Should I be striving to always
reduce LDL and increase H
DL? Is that a reasonable goal? And if so, is dietary cholesterol the
primary determinant of that? And just as a final point about this, I am aware of quite good data
that shows that anorexics, people that essentially eat no food, unless you force them to,
can often have very high LDL. So their dietary cholesterol
is essentially zero, and so they're manufacturing
a lot of their own. So realize this isn't your
primary area of expertise, but you're a smart guy and you think about this
kind of stuff
a lot. What do you think is going on with the cholesterol literature? And will we ever get to the bottom of this as a scientific and medical community? Because to me, it is rather perplexing. - It is, but you can get
through the politics. I know a fair bit about cholesterol 'cause it's in my family history. And I was headed for an early death, my grandmother had a stroke 30, that's how bad I am in
terms of my genetics. So I went on a statin, and I
know there's a lot of people who say that stati
ns long-term are bad. It's associated with Alzheimer's disease. I've been taking a statins since I was 29. And that's 'cause I forced my same doctor to give me the statin, the conversation was something like this. You're too young to be on a statin. And I said, what? You want me to have a heart attack before you give me
something, give it to me now. So 29, I'd been on a satin, and my cholesterol was
way up in beyond 300, which is a massive mess up. Basically my blood was creamy to look at. So I'
ve now got my cholesterol down to low, low levels to what would it be. You can check on my InsideTracker, but so my ratio of HDL to LDL, which you want to be less
than five, is now two, and the LDL is below a
hundred, so it's all good. And I've measured my
cardiovascular health with an MRI. I've got a movie of my heart beating. I've still got a heart of a
20-year old, so that's working, I'm willing to forgo the risk that the statin is causing problems later because of my family history. But othe
r people, I would say, be aware that statins
aren't perfect drugs. There were some interesting new ones. There's one called the PCSK9 inhibitor, which is, I think fortnightly,
every two weeks injection, that blocks the release
of LDL from the liver. And then that seems to be
great for lowering cholesterol, but also has other benefits
that might be prolongevity. And there were some people that I was just talking to
on the cutting edge of this, and their doctors are
trying them on this drug instea
d of the statin. So you could talk to your doctor about. - Do you avoid dietary
cholesterol for that reason also? Red meat, butter. I mean, I have been to love butter. I love red meat. I realized there's some people who don't. My cholesterol is a little bit high, but I'm working to bring that down a bit, although not by altering
my food intake yet. But what do you think is the relationship between dietary cholesterol
and serum cholesterol, and what's going on with the liver? Why are anorexics? W
hy is there a certain cholesterol so high when they're eating nothing? - Well, there've been in a
number of papers over the years that have been ignored. And our friend, Peter Attia, brought to my attention recently, a new study that I think definitively said that dietary cholesterol
has almost zero impact on blood cholesterol levels. - Good. - Yeah, so I'm annoyed
'cause I'd been avoiding eggs and butter for most of my
life and I didn't have to. So I have eggs- - Plenty of time, or
at least in
your case. - Yeah, yeah. So that's the thing. You can eat these foods
that were ones banned because it's very difficult to take cholesterol up
into the body from the gut. And most of it's being
synthesized in the body. - Well, I'm just pausing
there for a second because I think that it's
what we've been told. Six meals a day, eat a
lot of grains and fruits and this kind of thing, avoid cholesterol. I mean, basically everything we learned in the '80s and '90s and early 2000s is getting flipped on
its head now. But, and I think this
is a very strong caveat that's important to mention, amino acids. In particular, the amino acids that come from animal products, right? Seem to have some pro aging
effect on them, right? At least the way that I've
heard you describe your diet. And I'm somebody who
enjoys meat, I like it. But so I'm by no means, a vegan at all. But I've heard you say
you eat mostly plants, but a little bit of fish or chicken or something
of that sort of eggs or. But is that sp
ecifically to avoid excessive amino acid intake? Or is it something specific about plants that excites you with
respect to? [chuckles] I mean, vegetables are
delicious too, but what is it? Is it something great about plants or is it something bad
about when I think of meat, I guess the biologist in me
thinks amino acids, right? I don't think top sirloin,
I think amino acids. And I think top sirloin as I'm eating it, but really what they are, are amino acids, including leucine. - Yeah, well, ther
e are two
good things about plants, and neither of them is taste for me. I would eat steak all the time if I could. I did when I was a kid, I'm an Australian. But plants have two benefits. One is that they're highly nutritious, and they'll give you a lot of the vitamins and nutrients that I need. I don't take multivitamin, I don't want to have the
excess iron in my body. So there's that high density nutrition. So those dark leaves, if
it's a spinach salad, great. The second is that there is what
's called xenohormetic
molecules in plants. That term, xenohormesis is a term that I came up with
with my friend, Conrad. How it's, which means
stressed plants make molecules that benefit your health. I'll break it down. Xeno means between species,
and hormesis is the term, whatever doesn't kill
you makes you stronger and live longer. And the idea is that when
plants are stressed out, think of a great vine that's dried out and then starting to harvest the grapes, which is typically how it's done
. They are full with resveratrol, because resveratrol is
a plant defense molecule that I think is made to activate those
sirtuin genes in a plant. So plants have sirtuins just like we do. But by purifying or at least concentrating in a light-proof bottle and
keeping it out of the air, we stabilize the xenohormetic molecule, or it's a cocktail, not just
one, there's others in wine. We then ingest those and get the benefits of activating our own defenses, because our food was getting stressed out.
And by stressed, I don't mean
psychologically stressed. I mean, biologically stressed. And so I try to eat plants that have gone through a bit of stress. They might be brightly colored,
they've had too much sun or got nibbled on by a caterpillar. So you go to places where it's
organic or it's fresh, local, and those are the plants
that aren't perfect, and they probably have high concentrations of these molecules. And in addition, I also
buy the supplements to make sure I'm getting
enough of tho
se as well. - Which supplements mimic that? - So resveratrol will, there's another one called quercetin, or quercetin, some people call it, what you find in trace
amounts in apples and onions. And we also showed back in 2003 that it activates sirtuins as well. But others have, 20 years later, found that it kills senescent cells or helps kill senescent cells. So it's a double whammy
with that molecule. - And are you actively
picking out the peaches that look like they were
nibbled on by a caterpi
llar? - No, but I don't worry if
they've been banged up a bit. - What's the story with antioxidants? Are they of any value whatsoever, because the way that you
describe them at the beginning, and what I've heard recently is that they are not all
the rage for anti-aging. What are they doing that's useful? Should we be seeking
out antioxidants anyway for other seller health purposes? - Well, yeah, antioxidants
are not going to hurt you unless you take mega doses. We do need some oxidants
for our i
mmune system. And there's even, what's
called mitohormesis, which is your mitochondria power packs, need to have a little bit
of these free radicals to be able to function. So you don't want to overdose
on these antioxidants, vitamin C, vitamin E, don't overdo it. - You don't take a multivitamin, correct? - Right. - I think I'm going to stop
after this conversation 'cause I've always just taken one for the kind of insurance purpose, which is a stupid purpose. Not actual insurance, but just think
ing, oh cap top off on my ACBD. - Right, and I'll pee out what
I don't need, right, sure. - But that never bothered me. The whole expensive pee thing never got. That argument never got
made because of that. A good vitamin is not that expensive. I just figured better safe than sorry, but it may be that it's detrimental. - Well, it can in the case of iron as we discussed and the antioxidants. So when I came into the aging
field in the early 1990s, it was all about antioxidants. And we thought that
enzymes
by the name of catalyze and superoxide dismutase, well, they're going to be the key to longevity. It turns out that it's
largely been a failure that giving animals and
humans antioxidants, haven't had the longevity
benefits that we dreamed of. And the main reason is that
there's a lot more going on than just free radical damage. The epigenome gets disrupted, we've got these proteins misfolding. And so the problem really has
been that we didn't realize that you need to turn on the body's
natural defenses against that plus a whole host of other
things to get the true benefits. But I'm not going to say
it's a problem taking it, an antioxidant drink, pomegranate juice for one
is full of good stuff, including xenohormetic molecules. But resveratrol is a good case in point, which is when I worked on resveratrol as a longevity molecule, first we showed it in yeast
and worms and flies and mice. Before that, it was
thought that resveratrol was good for your heart in red
wine when you d
rink red wine, because it's an antioxidant. So then we showed that
it extended the lifespan of yeast cells through this
genetic pathway, the sirtuins. And we then tested whether resveratrol, if we change one atom to make it not an antioxidant, guess what? It still worked fine. So it wasn't its anti-oxidant activity that was extending lifespan. It was its ability to turn on the yeast's defenses against aging. Conversely, when we gave
the yeast antioxidants, they lived shorter. So yeah, that was t
he
beginning of my transformation into thinking turn on the body's defenses, don't give it the antioxidants. - This is an opportunity
for me to say something that I've been wanting
to say for a long time, which is that, what's so
wonderful about science is that because the goal is mechanism, you can really start to understand as you just described, what
actually mediates a process is very different than
what modulates a process. I mean, if a fire alarm goes
off in the building right now, it's go
ing to modulate our attention. That doesn't mean that it
controls our attention, it's not mechanistically relevant. And so I think this
thing about antioxidants is one of these cases, it sounds like where it's
in the right ballpark, but until one really unveils
the mechanism as you have, you can be, one can or in a field, can be badly wrong for a
very long period of time. It sounds like the sirtuins and really getting down to
the guts of the machinery of what causes cells to age
is really what i
t's about. Zooming way out, what
are the behavioral tools that one can start to think about in terms of ways to modulate these? Basically the way that DNA is being expressed and functioning. I've heard you talk before about hormesis of other
sorts, cold exposure. We talked about fasting. We talked about exercise in broad terms, but what about any evidence, if it exists, as to whether or not aerobic training versus weight training,
these sorts of things. In other words, what
are the sorts of thin
gs that people can do to improve
their sirtuin pathway? And I realized that there are caveats. We can't go directly from
a behavior dissertations, but in the general theme, what can people do, what do you do? - Right, well, we know
that that aerobic exercise in mice and rats raises their NAD levels and their levels of sirt,
one of the genes goes up two actually, number one and number three. What we don't know yet
is what type of exercise is optimal to get them to change. We will learn, we're doi
ng work. Now it's revealed that we're doing work with the military in the US, to try and understand that kind of thing. And I'll always tell you and the public, when I don't know something
I'm not going to extrapolate. But what do I do? I base my exercise on the
scientific literature, which has shown that
maintaining muscle mass is very important for a number of reasons. The two main ones are, you want to maintain your hormone levels. I'm an older male, losing my testosterone
and muscle mass ove
r time. And by exercising, I will
maintain that and have, in fact, I probably haven't
had a body like this since I was 20. So that's one of the benefits
of having this lifestyle. - Sorry to interrupt you. You do know we did an episode on hormones and there are data in humans that show that there are some
males in their '80s and '90s where their testosterone is equivalent to the average of 25 and 30-year-olds. I can get you that information, is really impressive studies. Unfortunately, they didn'
t
include a lot of information about the lifestyle factors, et cetera. But this idea that testosterone
goes down with age, it might be the trend, but it's not necessarily a prerequisite. - Right, I believe in naturally increasing and maintaining these hormone levels and I've been measuring
them for a long time. And I could see for me,
my testosterone levels were steadily, levels were going down. - And then you got tenure
and they went back up again. [both chuckle] - No, I actually became complac
ent. And it was the worst. Actually my age changed in the
wrong direction after that, 'cause I was relaxed. - Interesting. - And not worried about the future. But then I got serious. And I actually, according to
the InsideTracker algorithm, got my age down from 58 to
31 in a matter of months. So that was a big drop. And I've been getting steadily younger over the last 10 years, according to that
measurement, the blood test. - What about estrogen? Because women are different in the sense that the
y do the number of eggs that they, and the ovaries change over time, right? Do you think that they can
maintain estrogen levels in over longer periods of time using some of these same protocols? - Well, yeah, I get into trouble
from a certain university when I talk about this too much. - About estrogen? - Just about fertility and long story. I don't want to get too
much into the anecdotes, but I'll tell you the science, which is that if you take a
mouse and put it on fasting or caloric restricti
on
for up until the point where it should be in fertile, so that's about at a year of age, a mouse gets infertile, female mouse. - Due to fasting or
due to simply to aging? - Due to aging, due to aging. The fasting, it's not extreme fast, it's just less calories. Then you put them back on a regular food, and they become fertile again for many, many months afterwards. So the effect on slowing down aging is also on the reproductive system. - Interesting. - And so that, I wouldn't
say to any woman,
I wouldn't think that they
should become super skinny to try and preserve fertility,
that's not what I'm saying. But these pathways that we work on these, sirtuins are known to delay
infertility in female animals. Case in point, I'm one of the lead authors on a paper where we used NMN. Remember, this is the gas, the fuel, the petrol for the sirtuins. We gave old mice. One group of mice was 16 months old. Remember they became infertile
at 12, gave them NMN. And I think it was only six weeks late
r, they had offspring. They became fertile again, which goes against biology,
the textbook biology, which is that female
mammals run out of eggs. Turns out that's not true. You can rejuvenate the
female reproductive system, and even get them to
come out of mouseopause as we call it. So that's a whole new
paradigm in biology as well. - That's super interesting. Sorry to interrupt you, but I'm reminded by a set of studies that were done by your former colleagues 'cause they're no longer there, Dav
id Hubel and Torsten Wiesel, my scientific great grandparents. Won the Nobel prize for discovering, what are called critical periods, this phase of early development when the brain is extremely plastic. And a big part of their work was to show that after a certain point, the critical period shuts down, essentially the brain can't
change or not nearly as much. And then people came
along later and showed that you could open up these
critical periods again, but very briefly, and it takes a very spe
cific
stimulus, essentially, high degrees of focus, et cetera. However, there's a well-known
phenomenon in this literature where if you take an
animal and to some degree, this has been shown in humans as well, and you let them pass
through the critical period, but then you essentially
sensory deprive them. You take away experience,
you close both eyes. You essentially reopen
the critical period. So it seems like I couldn't
help but mention this, that there's this parallel between what we're talk
ing
about here with fertility and neuroplasticity, where yes, there is a timer where
certain things are available to the organism early in life, and then they tend to taper off. It's not an open and
shut, but they taper off. But then a deprivation
can actually reactivate the availability of that process. Forgive me, I just couldn't
help him mention it, but to me, so both of those things
are associated with youth, fertility and neuroplasticity. And so I think that
it'd be so interesting. I'd love
to collaborate with you on this to explore how neuroplasticity
might actually be regulated by these things like the sirtuins. - Right, and the sirtuins
do control memory in neurons as well. So what I think is really interesting is that what we're learning from work that you and your colleagues have done and in my lab as well, is that the body has
remarkable powers of healing and recovering from illness and injury. And what we once thought
was a one-way street and you just can't repair, or you c
an't get over these diseases, you can reset the system, and the body can really get rejuvenated in ways that in the future will wonder, why didn't we work on this earlier? The future of humanity is more like us walking
around like Deadpool. We'll probably be cleaner, and we won't smell as badly, but Deadpool, if you don't know, can get injured and just recover. It's very hard to injure this guy, and we're going to be the same. There are many species
you cut off the limb, the limb grows back. - S
alamanders or. - Yeah. We are now learning how
to tap into that system. And in part, what we're doing is reversing the age of those cells, and telling them how to read
the genes correctly again, reversing the age of that epigenome. And when you do that, the cells, the brain, for instance, the skin. We did the optic nerve. - Let's talk about those
results for a second. Then I want to make sure that we return to some of these behavioral protocols. You have this amazing paper
at the end of last yea
r, cover article, full article in nature, showing that essentially a small menu of transcription factors, which control gene expression, et cetera, could essentially reverse
the age of neurons in the eye and rescue those cells against damage. Essentially allow blind mice to see again, and offset degeneration
of these retinal cells, incredible paper, and
such a boom to the field. Where does that stand now in
terms of human clinical trials? I mean, how do, what are you envisioning in terms of the
trajectory of those data from mice into human someday? - Right, well, to get to
the point immediately, we're going to be testing
the treatment on monkeys, just for safety reasons. And then the first patient
should be done sometime in 2022, early 2023, and we're going
to try to recover blindness. - This involves making an injection of a virus into the eye, right? Right now, there's no
way that I am aware of to manipulate these transcription factors through a pill or some other? - And that's why,
we working on in my lab at Harvard right now. So it will be- - It will base moderation of- - Well you pop a pill in the whole body gets rejuvenated by 20 years. That's what we're aiming for. Now we do it with gene therapy
in the eye and other places. So in the IES, it's single injection, the genes go into the retina
and we can turn it on, with a drug called doxycycline. And we do that in the mice
for four to eight weeks, then the eye gets younger. We can measure that' cause
you can measure the c
lock. And then the vision
comes back in those mice. And I don't see any reason,
why it shouldn't work in people because it's the same structures
and mechanisms that are on in the human as well. Now these- - And it's one injection. - It's one. - I should mention injections into the eye obviously nobody should do this outside of a ophthalmology clinic. And there definitely by
an ophthalmologist but, the injections into the eye
are painless if done correctly by the right person. It sounds dreadful,
but it's actually, I've seen it done hundreds of times. I've done it, thousands of times and it's not to myself,
but to other creatures. And there's a way of doing this as completely painless to the person- - Oh you don't feel it. It's a tiny, tiny needle too. But the great thing about this is that it's a one-time treatment. Those genes go into the back
of the eye and stay there, forever. And you can just turn
them on whenever you want. So what we found is you can
turn them on in the mice, they
get their vision back, and then you turn it off again. And so far, many months out, the benefit has remained, but if it does decline, we'll just turn it back
on and reset the system, rinse and repeat. So one day what's exciting is that we could potentially do
this across the entire body and just take this antibiotic, every five years and go
back time and time again. - And thinking about the body and what's going on under
the head I'm amazed, still that there isn't a
simple, affordable technolog
y that would allow me to just
look into my body and see whether or not there are
any tumors growing anywhere. I mean, it's not that hard
to look into the body. I mean that the technology exists. why hasn't anybody created an at home or pseudo at home solution,
like a clinic where you can go and pay 50 bucks or a hundred bucks and see if you have any
tumors growing anymore. - Yeah, it's still expensive. You can get your doctor
to try to get you in, there's some companies
that offer blood tests th
at look at circulating DNA, that'll measure it. We're getting there. It's still probably five to 10 years away from being really cheap. You can do things like a
colon cancer test at home. I think it's a hundred
and something dollars. You ship off your shit,
excuse my language, and they measure it. And they tell you if
you've got colon cancer, with high probability, I did that during the pandemic because I didn't want
to get a colonoscopy. - Mhmh, is it more accurate or
as accurate as a colonosco
py? - I believe it's close
to being as accurate. The downside is that during a colonoscopy, they can pinch off the polyps
that are looking dangerous, whereas this obviously isn't that, but it's certainly easier to do. And my father who's
Australian tells me that it's free for Australians. They get this test routinely. - Mhmh, interesting. I want to return to the topic
that I took us away from. So I apologize, which
is behavioral protocols. Do you regularly do the cold shower thing? Ice baths, co
ld water swims,
are you into that whole biz? [David chuckles] - Well, you do know that
I've done it at least once 'cause we did it together. - That's right. Not the same bath, just to be very clear, same sauna, different ice baths, [David chuckles] the idea of Sinclair and Huberman taking an
ice bath together it's a, it might warm some people's hearts, but just to be very clear, different, same ice bath, different, different times. - Yeah, thank you for clarifying. - [Andrew] Yeah. I don't do th
em regularly. I do try to sleep cool. I sleep better anyway. I try to dress without
a lot of warm clothes. I'm here in a T-shirt and
it's middle of summer, but in winter, I'll try
to wear a T-shirt too. - So you're challenging your
system to thermoregulate? - Right, right. I've got this, hypothesis with Ray Cronise. We published what's called The
Metabolic Winter Hypothesis, which is, few tens of
thousands of years ago, we were either hungry or cold or both and we really experience that now. And
so, we try to give
ourselves the metabolic winter and part of the problem I
think with the obesity epidemic is that we're never cold and cold, when you're cold you have to burn energy. It may be only slightly,
but over the whole night, if you're a little bit cool, you'll actually expend more energy. So I try to do that, but I'm not a big fan of cold showers. The sauna, I don't have access
to my gym as much as I did. So, but I do want to get back into it. I used to do it regularly with my son an
d I posted on Instagram once that he could stay in there for 15 minutes and I could only stay in for about three. Anyway, long story short, I try to compensate with
changes in my diet and exercise until I get back into it. - You reminded me of something
that I meant to ask earlier that obesity reduces NAD
levels and accelerates aging. How? I mean, okay. So again, this is the, the scientist in the us, so someone's carrying a lot
of excess adipose tissues, subcutaneous and, visceral fat. But why s
hould that reduce NAD in any ways that are independent of
effects on glucose and insulin? If it, you know, is there's something direct
about white adipose tissue. And the reason I ask this, is not simply to dig into mechanism alone, but I think there are
really interesting data now that fat actually gets neural innervation. I mean, it's not just a, it's not just stored fuel. It's stored fuel, that's acting as an
endocrine organ, essentially. So, why would being fat
make people age faster? - Yeah
, that's a question that, is so obvious, but so few people ask it, that's what makes you a good scientist. And so that we don't know, but I'll give you my best
answer, which is that, obesity comes along with
a lot of problems that, include a lot of senescent cells in fat, if you stain old fat for
senescent cells, it lights up. - Mhmh. And when you kill off those cells, at least in mice, and maybe in humans, it looks like the fat is
less toxic to the body. 'Cause those senescent cells
in their fa
t are secreting these inflammatory molecules that will accelerate aging as we now know. We talk about the sirtuins in NAD. So if we, if we just look philosophically, at why this would be the sirtuins only, like to come on or get
activated when the body needs, is on the right adversity. And if a cell is surrounded by
fat or contains a lot of fat, it's going to think times a good, it doesn't need to switch on. So that's the evolutionary argument. Mechanistically, we don't know, but it could have s
omething to do with the response to glucose, which then responds to the sirtuin gene, but that hasn't been worked out very well. - And is there any evidence that leptin, this hormone from fat can actually, interact with the sirtuin pathway? - I don't recall seeing that- - Maybe I could do a
sabbatical in your lab and that'd be a fun one. - Definitely- - Because leptin during
development is what triggers, the permission for the hypothalamus
to enter puberty, right? - Yeah. - This is why kids that
eat
a lot when they're young and get overweight will also start to go and undergo puberty more quickly, although they have
reproductive issues later. - Well yeah. We should study the
hypothalamus together 'cause, the hypothalamus is, can control the aging of the body. - The most interesting part of the brain. [Andrew chuckles] - For sure. - Yeah, absolutely. - If you turn on the SIRT1 gene, the SIRT2 that we work
on, in the hypothalamus that actually, will extend lifespan. Also, it's been shown
by Dongsheng Cai at Albert Einstein College of Medicine, that if you, inhibit
inflammation in the hypothalamus, in a mouse, it will increase or maintain the expression
of what's called GnRH, which is the hormone that, he found actually controls
longevity in the mouse in part. And so keeping inflammation
down in the hypothalamus, is sufficient to extend
the life span of animals. And I reviewed that paper for nature all about seven years ago. And that was the first demonstration that the hypothal
amus is one
of the leading regulators of the body's age. - I find this fascinating GnRH, for those of you that don't
know actually comes from neurons in the hypothalamus that then, literally reached down into the pituitary and trigger the release of
all the things that control fertility, luteinizing hormone, follicle-stimulating hormone, et cetera. It's such a powerful set of neurons, and it's never really been clear, what at a behavioral level
triggers the release of GnRH. There's all the stori
es about pheromones and timers and puberty, et cetera, but environmental conditions
and dietary conditions and behaviors that can
control GnRH release, I think, is an incredible area for exploration. I'd love to do that sabbatical by the way. I have a couple, well
seemingly random questions, but I can't help, but ask
because one thing I like to do is forage the internet for
practices that at least more than a few people are doing, and then wonder whether or
not there's any basis for it. You ment
ioned methylation
as a detrimental process, the way it disrupts the
epigenome and the CD reader, so to speak. There are people out there who
are ingesting methylene blue. And when I was a kid, I used methylene blue
to clean my fish tank. And I love fish tanks. I know you're into aquaria also, a different podcast episode,
we'll talk about aquaria, but why in the world, would
people ingest methylene blue? Meaning is their logic correct? And or is that a dangerous practice? I'm not sure I'd want to
ingest methylene blue, sounds not like a bad thing to do. - It stains your body if you've
seen, yeah methylene blue- - Yeah, there was someone
in my lab as a postdoc was using it to study a
completely different process related to the blood-brain barrier and used to inject into animals
and they would turn blue, but then again, people
ingest colloid silver. You know they'll put
in there, there's this, please people don't do this or if you do, just don't tell me, 'cause I won't like it. They, peop
le put it in their eyes and some people actually stain their skin. They actually become kind of
a silver purple brown color if they do it excessively. I mean, there's a lot of
crazy stuff out there. But what do you think they're thinking with this methylene blue thing or should we just get them
to a good psychiatrist? - I don't know, for sure. I think methylene blue was found to extend the lifespan
of some lower organism and that's where it came from. My recollection- - With the emphasis on lowe
r organisms. - Yes smaller organisms. I think doesn't, do you
remember Andrew does it, interrupt or interfere
with mitochondrial activity and that's- - Maybe that's why the are doing it. - Yeah.
- [Andrew] Okay. - We need to look this up and post it. - [Andrew] Okay. - We'll get to the bottom
of this, but those methods, let's talk about those. - [Andrew] Yeah. - Those methods have to
be placed on the right, part of the genome. They get attached to the right
genes in the wrong genes. And if you h
ave a lot of methylation, it's going to mess up the epigenome. Smoking will do that, lack of
exercise, all that good stuff. So you, what you actually want
to do is you want to measure it and make sure what you're
doing with your body, is working. How do you know that if you do this or that is actually helping. And so you can test your age. I could take, a swab from your mouth and tell you how old you are biologically. And then we could work on
trying to bring that down and actually there were an
ecdotes now, that people are reversing
their age by a decade or more just by doing some of the
things that we've talked about and some other cutting edge stuff that I'm going to write about. But yet, but you have to measure stuff. That's, I didn't want to
forget to bring that up. I'm measuring stuff all the time. I have blood tests like you, I've got this monitor that
stuck to my chest right now that's measuring myself
a thousand times a second and I measure my biological age. - What's it measur
ing a
thousand times a second? A huge list of things. - Yeah, yeah. So this, this little device is stuck here and it's for two weeks
that you just recharge it or send it back and get a new one. It's got a body temperature movement, heart rate variability. It's an FDA approved
device, it's not a toy. It's not one of these recreational things. It also listens to my voice, eventually will me if
I need a psychiatrist or if I'm depressed, it will tell me how I sleep, obviously. But when you put all t
hat data together and it's individualized and anonymized, it can now tell my doctor in real time, if I've got a cold that
needs an antibiotic, or it's just a virus. If I am suffering from COVID-19 or even if I'm going to have
a heart attack next week. And so these little devices
are going to be with us all the time, instead of going
to your doctor once a year, which is ludicrous. - I have to ask you about x-rays. 'Cause every time I go through
the scanner at the airport, I think, "Sinclair would
never do this." And the argument I heard
you give about this before was a really excellent one, which is that it's a low level amount of radiation, going through at the airport, but the argument is always, well, it's just as much as on the plane and your argument, your
counter-argument I should say was, "Well then why would I
want to do both, right? Why would?" So when you go to the airport, assuming you're not running late and you have to go
through the standard line, what do you say to them?
And do you say, "I'm David Sinclair." And then they shuttle
you to your own line. What do you say? You do say, "I don't like this thing." Do you have to give them a reason? - No, you don't. You can say, "I don't want this." And they'll get annoyed
'cause it's hard for them to pat you down, but you get a pat down and you you're done as long as you're not
in a hurry, it's fine. If you want to pay for
the TSA Pre in America or the way to get around those
scanners, you can do that. So I travel a lot
, so
it's worth it anyway, but I just go through the metal detector, I don't get scanned. - And the metal detector
doesn't have the same, same problem. And what about x-rays at the dentist? Yeah. - Well, you know one x-ray
is not going to kill you. Two's not going to kill you, but I- - Three will kill you. No, I'm just kidding. [Andrew chuckles] - I try to limit it
because it's cumulative. - Right. - And I went for six years
without having a dental x-ray and then my last visit, I just gave up. I
was tired of arguing with my dentist. So they gave me one, but they've got led coats on and they put lead all over your body. That's telling you something right there. And funnily enough, my
teeth hadn't changed. Now you can balance that by saying, "Well, one x-ray, two x-ray, three x-rays is worth
it if I have cavities." And that's true, you want to know what's in there, but doing it regularly, for me, I don't think it was worth it because it, my teeth are in perfect
health and I've always bee
n, I don't have any cavities,
didn't have braces, they're fine. So stop scanning me. I mean, I know you have
to pay for the machine, but you know, do I have a choice? Yes, so stop pressuring me. - You know, who shared your
sentiments about x-rays and the dentist in general? My apologies to the dentists out there, was the great physicist, Richard Feynman. This is a story about him that's
not especially well-known, but he had very serious
concerns, health concerns, about x-rays because he
understo
od the physics and he understood enough biology that, he was actually quite vocal about his, dislike of dental
technology and its dangers. And he talked about some of that. People can find that on
the internet, if they like. Speaking of people who, are like Feynman, who've been engaged in public
discourse about science. One of the things that I
appreciate about you, in fact, the way that you and I, initially came to know one
another is through your public health education efforts. So, obviously
we're doing this podcast, you've done the Joe Rogan Podcast, Lex Fridman's Podcast, excuse me Lex, I'm still adjusting that. Lex Fridman's Podcast
and many other podcasts, you've written an amazing book. What are you thinking these days in terms of what the
world needs in terms of, education from scientists,
education from MDs, education in general as it
relates to these things because, I think if nothing else
2020 revealed to us that there's a gap, there's a gap in understanding. And that the s
cientists too are guilty of, not knowing what to do
with all the information that's out there on pub med or elsewhere. I'm just, you know, what are you thinking for
yourself and in general, I'd like to just know, what do you think the world needs there? Maybe we can recruit some
more public educators. - Yeah. Well, we've gone from a
time, when you and I were, in college and young
professors where the only way, to get our voice out to
the public was either through a newspaper or a
very short radi
o interview, which for me was extremely
frustrating 'cause particularly the newspapers and my topic, every time was twisted into something that was not just embarrassing,
but Harvard university used to bring me into the back office and- - Frankenstein. - "How did you say such a thing? We're all going to live to a 250." I didn't say that. So, we're now also in a world where we're overwhelmed with information, and most of it is wrong and anyone can pretend to be an expert. So we've gone from early
days to now the future, and we're experiencing it right now thanks to guys like you, people like you, is that the experts, some experts, a small number who are
brilliant and good communicators are talking directly to the public. This has never been able to be possible, until this time, right now. So another five years from
now, and certainly by 10 years, I would hope that there are
trusted sources of information of people who can not just
communicate, the ideas directly, but are able to talk ab
out
things that are going on that aren't even published yet to say, "Here's what's really going on. And this is what the future looks like." But this is somebody, like yourself who spent their whole life
studying a particular topic and knows what they're talking about. And this, this is also something
that I think most people don't know that we
scientists, if we tell a lie, we burst into flames, we absolutely cannot tell
something, that's untrue. And to the best of our
knowledge, we say it as it
is, because if we don't, we're beaten up, and we, or we kicked
out of the university. So the people who survive to our age, and I'm a little older than you. So I've survived a bit longer. - But a lot younger inside. [Andrew chuckles] - Nah, but we have to measure you with- - Yeah we need, I probably need a little
help, hopefully not too much. - We'll measure that, and we'll work on your
eating, but this is really, really important is that, finally people like your are
allowed by our universitie
s to talk to the public. I used to do it, with a real threat to my survival. People would look at me, "Oh, he's a salesman, he's
promoting this and that." It was seen as a real
negative, but finally, I think we're in a world where, it's not negative anymore. And the pandemic showed that
we needed voices of reason, voices of fact, that you could trust. And you can see the
popularity of your podcast, shows that the public, they're desperate for
facts that they can trust, 'cause they don't know
wha
t to believe anymore. - Well, I'm being completely honest
when I say this, that, you know, I followed your lead. I saw you on the Joe Rogan
Podcast and my jaw dropped. I was like, "This is amazing, like this." Because, you get out other good
scientists on before but, you're tenure Professor Harvard Genetics, Department of Genetics. And for those of you don't know, there's the Harvard and of
course, Harvard Medical School and they're both excellent, of course, but these are the top,
top tiers of
academia. And I certainly understand
what it takes to get there and survive there and to thrive there, it's like a game of pinball. You never win. You just, you just get to, if you're doing really well,
you get to keep playing. And that's the truth in academia. And if you're not, you
stop playing basically. But when I saw you,
explain what you were doing in a way that was accessible to people and also talking about, possible protocols that they
might explore for themselves to see if those were,
right for them. I was just, I was just
dazzled and excited, and I made every effort to
get in contact with you. And, the rest is history, but, I think what's really
exciting to me these days is because of 2020 and with
everything that's happened and it continues to happen. There's a thirst for knowledge. There's also this direct
to the public route that you mentioned. And, I think there's also an openness, I'd love your thoughts on this, but it seems to me that
there's an openness in, from the g
eneral public, about health practices, that there are actually things
that people can do to control their stress level, to control, their sleep, to control their cholesterol if that's what they to
do, maybe they don't and to even control their lifespan, which I think is remarkable. And, I know I speak on
behalf of so many people, when I just, I want to say, thank you. You've, truly changed
the course of my life. I would not be sitting here doing this were it not for your example. And I always sa
y Sinclair,
many people have written books, many academics have
written books, as you have, but in terms of doing podcasts and really getting out there
with your message in a way that I have to assume raised
your cortisol level and heart rate just a little bit, but you did it nonetheless. You are truly first man in and that, that deserves a nod. And, I have a great debt of
gratitude to you for that. So thank you so much. - Oh thanks, Andrew. You're a, you've become a good friend and I'm super pr
oud of what
you've done and what you, I know what you will do. - So in addition to your book and your presence on social
media, Instagram, and Twitter, and appearances on podcasts, recently I've noticed
that you've opened up, a survey email/website
that people can, access, excuse me, to get some information
about their own health and rates of aging. Tell us about that and
what's being measured. And what is this test that
you've been working on, secretly and now soon, not so secretly. - Yeah, wel
l that, what I want, is a credit score for
the body to make it easy for people to follow their health. And there is a number, there's a, there's a biological age
that you can measure. Unfortunately, the test is many hundreds
of dollars right now, but in my lab, we've been
able to bring that down a lot. And so I want to democratize this test so that everybody has access to a score for their health that can predict their, not just their future
health and time of death, but to change it. And I'm bu
ilding a system
that will point people in the right direction and give them discounts for certain things that will improve, not
just their health now, but 10, 20, 30 years into the future. And we can measure that, and very cheaply, keep
measuring it to know that you're on the right track, 'cause if you don't measure something, you can't optimize it. And so this is the biological age test, we've developed it, it's
a simple mouth swab. We're rolling it out. We're building the system right now. And
there was a sign up sheet 'cause a lot of people
want to get in line, go to doctorsinclair.com, you can get on that and you'll be one of the
first people in the world to get this test and see what we're doing. - Oh, fantastic. Will people be celebrating their, biological age birthdays? In other words, if I'm
minus, like if I can imagine, so I'm 45 right now, soon to be 46. But if I, if I were to be so lucky as
to get my biological age to 35 within 12 months, maybe
you can help me do that. Do I
get to celebrate, a negative birthday? - Absolutely. And my plan is that those
people who take their age back a year or more, we think we can
go back 20 years eventually, they'll get a birthday card from me and it's a negative birthday card. [Andrew chuckles] - I love it. And probably very little, actual birthday cake being ingested but, who cares 'cause you're
living that much longer. - That's full of stevia,* that'll be fine. [Both chuckle] And thank you for talking to us today. I realized I t
ook us down deep
into the guts of mechanism and as well, talking
about global protocols, everything from what one can
do and take if they choose, that's right for them to, how to think about this
whole process that, that we talk about when
we talk about lifespan as always an incredibly illuminating. Thank you, David. - Thanks Andrew. - Thank you for joining
me for my conversation with Dr David Sinclair. If you're enjoying and or
learning from this podcast, please subscribe to our YouTube channel
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which has also hubermanlab. So be sure to check those out. A lot of the material, covers things similar to the podcast, but oftentimes I'll
cover a unique material, not featured at all on the podcast. So that's hubermanlab on
Instagram and on Twitter. In addition, we have a Patreon, it's patreon.com/andrewhuberman. And there you can support the podcast at any level that you like. Today, and in many other
previous episodes of the Huberman Lab Podcast, we discuss suppl
ements. While supplements aren't
necessary or right for everybody, many people derive tremendous
benefit from supplements. For that reason, we partnered with Thorne, T-H-O-R-N-E, because Thorne Supplements are the absolute highest quality and the absolute highest precision, meaning what you see listed on the bottle is what's actually in the bottle, which is not the case for many supplement companies out there. Thorne is one of the
partners of the Mayo Clinic and all the major sports teams. And s
o they really are very
trusted, very highest quality. If you want to see the supplements
that I personally take, you can go to thorne.com/u/huberman, and there you'll see the
supplements that I take, you can get 20% off any
of those supplements. And if you navigate deeper
into the Thorne site, through that portal, you'll also get 20% off any
of the other supplements that Thorne makes. So again, it's Thorne, thorne.com/u/huberman to get 20% off any of the
supplements that Thorne makes. Also take
note that the
lifespan podcast featuring Dr David Sinclair as a host, launches Wednesday, January 5th, you can find the first episode here on the Huberman Lab Podcast channel. They also have their
own independent channel. You can find the link to that
channel in the show notes. So please go there, subscribe on YouTube, also on Apple and Spotify. I've seen these episodes,
they are phenomenal, and you're going to learn
a tremendous amount, about aging and how to
slow and reverse aging from the wor
ld expert
himself, Dr David Sinclair. And last, but certainly not least, thank you for your interest in science. [upbeat music]
Comments
The first episode of Dr. David Sinclair's new podcast launches Wednesday, January 5, 2022. You can subscribe now to that podcast, "Lifespan with Dr. David Sinclair", on all podcast platforms ( https://lifespanpodcast.com ) and here on YouTube: https://www.youtube.com/davidsinclairpodcast. Thank you for your interest in science!
My father is 97 years old. He is a WWII vet and has survived double pneumonia, sepsis and Covid in the last two years. And he rides his recumbent bicycle 30 minutes daily. His longevity, in my opinion, is directly related to his low caloric intake (and great caretaking). He’s eaten once or twice per day for his entire life. Super interesting science. Thank you.
Welcome to the Future everyone, where golden information like this is free and available instantly.
I'm extremely impressed with Dr. Sinclair's insights on aging - it's incredible how much progress is being made in understanding our biology! I recently heard about a study that showed certain dietary modifications could extend lifespan and I'm excited to see what other discoveries we uncover on this fascinating topic!
Why I love Dr. Sinclair. He always answers so honestly. “We don’t know, but I’ll give you my best answer.” I appreciate you both for taking the time to educate us!
my friends: eating unhealthy my friends at 50: hOw dO yOU LoOk sO YoUnG?
Menopause is brutal. It led me to David Sinclair and life changes... i feel so much better but still not the same as before. We desperately need more research to address this bro real issue affecting over half the population.
Dr. Huberman is really creating an amazing legacy of information. The only problem I have with him is that I get lost in those eyes and forget to listen.
Two scientists that I follow all the time, now on one podcast. This is a Christmas gift.
In addition to the generosity and vast knowledge provided, can we all agree that this podcast is most enjoyable due to the fact that these two gentlemen utilize the art of conversation very well? No interrupting, grandstanding, one upmanship, talking over one another. A lost art, indeed. Well-directed by Dr .Huberman and cooperative responses by Dr. Sinclair. Riveting!! Thank you both!
Absolutely LOVE how Dr. Huberman handles this - he carefully brings out all the right things. Fantastic interview!
I have to say that the obvious enthusiasm and excitement you both show as you discuss these topics is absolutely wonderful.
Imagine how the internet has changed the world. You can now easily prolong your life for free because of technology and intelligent people like Andrew
I am a practicing physician assistant and went into medicine because my family has always been on the wholistic/ natural path. We grew our own veggies, bought farm fresh eggs and grass fed local beef, had fruit trees and grape arbors. We ate fruits and veggies all day. We were physically active all day. My father is 93 and not on any meds. My mom is 89. They do not smoke and rarely drink alcohol. They have never had cancer, diabetes, dementia, heart disease. I have been telling patients for years that it is not rocket science and the best treatment I can give them is to eat only to live and keep moving. I could talk for hours about this! Our food production and lifestyles are killing us. It is that simple!! I would love to help get more of this information out there! And I would love to meet you both! Thank you and Keep up the great work!
Dear Andrew, I want to give you a huge shoutout and express my gratitude for all the awesome info you're putting out there hosting such great minds and the incredible work you're doing to make education accessible. On top of all the cool science stuff, your subtle sense of humor really adds to the experience. Watching your videos is a blast! Thanks a ton!
Angina completely gone since taking reservatrol and NMN. Also doing intermittent fasting. Amazing info thank you. Life changing literally.
What a gift for us, your audience. I do the fasting at 74 and feel great. Implementing new ways to maintain good health, never felt so good! Thank you both for you kindness and willingness to share .
This channel/show is a gift to mankind and we should be forever grateful to this man
I can’t believe this content is free. Thanks docs!
The best what I like about how Andrew is handling an interview is that he really does not interrupt. In this case its even more important than saying things.