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2021-12-27 - Interview Dr. David Sinclair - Huberman Lab Podcast - The Biology of Slowing & Reversing Aging: Difference between revisions

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== Transcript ==
== Transcript ==
 
=== Dr. David Sinclair, Harvard Medical School ===
=== 00:00:00 Dr. David Sinclair, Harvard Medical School ===
{| style="padding-top: 1em;"
- Welcome to the Huberman Lab podcast,
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:00
 
| - Welcome to the Huberman Lab podcast, where we discuss science and science-based tools for everyday life.
where we discuss science
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:09
and science-based tools
| I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine.
 
|-
for everyday life.
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:15
 
| Today, my guest is Dr. David Sinclair, professor of genetics at Harvard Medical School and co-director of the Paul F. Glenn Center
I'm Andrew Huberman,
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:22
and I'm a professor of
| for the Biology of Aging. Dr. Sinclair's work is focused on why we age
 
|-
neurobiology and ophthalmology
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:27
 
| and how to slow or reverse the effects of aging by focusing on the cellular and molecular pathways
at Stanford School of Medicine.
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:33
Today, my guest is Dr. David Sinclair,
| that exist in all cells of the body and that progress those cells over time from young cells to old cells.
 
|-
professor of genetics at
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:40
 
| By elucidating the biology of cellular maturation and aging, Dr. Sinclair's group has figured out intervention points
Harvard Medical School
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:48
and co-director of the
| by which any of us indeed, all of us, can slow or reverse the effects of aging.
 
|-
Paul F. Glenn Center
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 0:53
 
| What is unique about his work is that it focuses on behavioral interventions, nutritional interventions, as well as supplementation
for the Biology of Aging.
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:00
Dr. Sinclair's work is
| and prescription drug interventions that can help us all age more slowly and reverse the effects of aging
 
|-
focused on why we age
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:07
 
| in all tissues of the body. Dr. Sinclair holds a unique and revolutionary view of the aging process, which is that aging
and how to slow or reverse
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:14
the effects of aging
| is not the normal and natural consequence that we all will suffer. But rather that aging is a disease
 
|-
by focusing on the cellular
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:20
 
| that can be slowed or halted. Dr. Sinclair continually publishes original research articles in the most prestigious
and molecular pathways
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:27
that exist in all cells of
| and competitive scientific journals. In addition to that, he's published a popular book
 
|-
the body and that progress
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:32
 
| that was a New York Times bestseller. The title of that book, is 'Lifespan: Why We Age And Why We Don't Have To.'
those cells over time from
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:38
young cells to old cells.
| He is also very active in public facing efforts to educate people on the biology of aging and slowing the aging process.
 
|-
By elucidating the biology of
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:45
 
| Dr. Sinclair, and I share a mutual interest and excitement in public education about science.
cellular maturation and aging,
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:51
Dr. Sinclair's group has
| And so I'm thrilled to share with you that we've partnered. And Dr. David Sinclair is going to be launching
 
|-
figured out intervention points
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 1:56
 
| the lifespan podcast, which is all about the biology of aging and tools to intervene in the aging process.
by which any of us indeed, all of us,
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:02
can slow or reverse the effects of aging.
| That podcast will launch Wednesday, January 5th. You can find it at the link in the show notes
 
|-
What is unique about his work
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:08
 
| to this episode today as well. You can subscribe to that podcast on YouTube, Apple,
is that it focuses on
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:13
behavioral interventions,
| or Spotify, or anywhere that you get your podcasts. Again, the lifespan podcast featuring Dr. David Sinclair,
 
|-
nutritional interventions,
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:19
 
| Claire begins Wednesday, January 5th, 2022, be sure to check it out. You're going to learn a tremendous amount of information,
as well as supplementation
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:26
and prescription drug
| and you're going to learn both the mechanistic science behind aging, the mechanistic science behind
 
|-
interventions that can help us all
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:31
 
| reversing the aging process and practical tools that you can apply in your everyday life.
age more slowly and reverse
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:36
the effects of aging
| In today's episode, Dr. Sinclair and I talk about the biology of aging and tools to intervene in that process.
 
|-
in all tissues of the body.
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:42
 
| And so you might view today's episode as a primer for the lifespan podcast,
Dr. Sinclair holds a unique
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:47
and revolutionary view
| because we delve deep into the behavioral tools, nutritional aspects, supplementation aspects
 
|-
of the aging process, which is that aging
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:52
 
| of the biology of aging. We also talk about David's important discoveries of the sirtuins, particular components
is not the normal and natural consequence
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 2:59
that we all will suffer.
| 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.
 
|-
But rather that aging is a disease
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:05
 
| Coming away from today's episode, you will have in-depth knowledge about the biology of aging at the cellular, molecular,
that can be slowed or halted.
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:12
Dr. Sinclair continually publishes
| and what we call the circuit level, meaning how the different organs and tissues of the bodies age independently, and how they influence
 
|-
original research articles
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:17
 
| the aging of each other. Today's episode gets into discussion about many aspects of aging
in the most prestigious
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:23
and competitive scientific journals.
| and tools to combat aging that have not been discussed on any other podcasts or in the book lifespan.
 
|-
In addition to that, he's
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:29
 
| Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
published a popular book
|}
 
=== ROKA, InsideTracker, Magic Spoon ===
that was a New York Times bestseller.
{| style="padding-top: 1em;"
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:35
The title of that book, is 'Lifespan:
| 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.
 
|-
Why We Age And Why We Don't Have To.'
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:42
 
| In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is ROKA.
He is also very active
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:48
in public facing efforts
| ROKA makes eyeglasses and sunglasses that are the absolute highest quality. I've spent a lifetime working on the visual system.
 
|-
to educate people on the biology of aging
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 3:54
 
| And I can tell you that the visual system has to contend with a number of different challenges, such as when you move from a bright area outside
and slowing the aging process.
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:01
Dr. Sinclair, and I
| to an area where there are shadows, you have to adjust a number of things in your visual system so that you can still see things clearly.
 
|-
share a mutual interest
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:07
 
| One problem with a lot of eyeglasses and sunglasses is they don't take that biological feature into account.
and excitement in public
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:13
education about science.
| And you have to take off your glasses and put them back on, depending on how bright or dim a given environment is.
 
|-
And so I'm thrilled to share
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:19
 
| With ROKA eyeglasses and sunglasses, you always see things with the utmost clarity. In addition, they're very lightweight
with you that we've partnered.
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:25
And Dr. David Sinclair
| and they won't slip off your face. In fact, they were designed to be worn while biking or running and the various activities,
 
|-
is going to be launching
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:30
 
| but they also have a terrific aesthetic, so you could wear them to dinner or work. I wear readers at night and when I drive and I wear the sunglasses for most of the day.
the lifespan podcast,
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:38
which is all about the
| If you'd like to try ROKA sunglasses or eyeglasses, you can go to roka.com, that's roka.com
 
|-
biology of aging and tools
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:43
 
| and enter the code Huberman, to save 20% off your first order. Again, that's ROKA, roka.com and enter the code Huberman
to intervene in the aging process.
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:51
That podcast will launch
| at checkout. Today's episode is also brought to us by InsideTracker. InsideTracker is a personalized nutrition platform
 
|-
Wednesday, January 5th.
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 4:57
 
| that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals.
You can find it at the
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:04
link in the show notes
| I've long been a believer in getting regular blood work done for the simple reason that many of the factors that impact your immediate and long-term health
 
|-
to this episode today as well.
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:11
 
| can only be assessed from a quality blood test. And now with the advent of modern DNA tests,
You can subscribe to that
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:16
podcast on YouTube, Apple,
| you can also get a clear picture of what your biological age is and compare that to your chronological age.
 
|-
or Spotify, or anywhere
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:22
 
| And obviously your biological age is the important one because it predicts how long you will live
that you get your podcasts.
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:28
Again, the lifespan podcast
| and it's the one that you can control. The great thing about InsideTracker is that compared to a lot of other DNA tests
 
|-
featuring Dr. David Sinclair,
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical-align: top;" | 5:34
 
| and blood tests out there is that with InsideTracker, you don't just get your numbers back at the levels of various hormones, metabolic factors,
Claire begins Wednesday,
|-
 
| style="min-width:4em; color: grey; text-align: right; padding-right: 1em; vertical
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 sirtuins, 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 of aging
 
and tools to combat aging
 
that have not been discussed
 
on any other podcasts
 
or in the book lifespan.
 
=== 00:03:30 ROKA, InsideTracker, Magic Spoon ===
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 eyeglasses 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
 
of different challenges,
 
such as when you move
 
from a bright area outside
 
to an area where there are shadows,
 
you have to adjust a number of
 
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
 
biological feature into account.
 
And you have to take off your
 
glasses and put them back on,
 
depending on how bright or
 
dim a given environment is.
 
With ROKA eyeglasses and sunglasses,
 
you always see things
 
with the utmost clarity.
 
In addition, they're very lightweight
 
and they won't slip off your face.
 
In fact, they were designed to be worn
 
while biking or running
 
and the various activities,
 
but they also have a terrific aesthetic,
 
so you could wear them to dinner or work.
 
I wear readers at night and when I drive
 
and I wear the sunglasses
 
for most of the day.
 
If you'd like to try ROKA
 
sunglasses or eyeglasses,
 
you can go to roka.com, that's roka.com
 
and enter the code Huberman,
 
to save 20% off your first order.
 
Again, that's ROKA, roka.com
 
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 been a believer in
 
getting regular blood work done
 
for the simple reason
 
that many of the factors
 
that impact your immediate
 
and long-term health
 
can only be assessed from
 
a quality blood test.
 
And now with the advent
 
of modern DNA tests,
 
you can also get a clear picture
 
of what your biological age is
 
and compare that to
 
your chronological age.
 
And obviously your biological
 
age is the important one
 
because it predicts how long you will live
 
and it's the one that you can control.
 
The great thing about InsideTracker
 
is that compared to a
 
lot of other DNA tests
 
and blood tests out there
 
is that with InsideTracker,
 
you don't just get your numbers back
 
at the levels of various
 
hormones, metabolic factors,
 
blood lipids, et cetera,
 
but it also offers clear
 
directives to lifestyle factors,
 
nutritional factors and
 
supplementation that you can use
 
in order to get the
 
numbers into the ranges
 
that are best for you and for your health.
 
If you'd like to try InsideTracker,
 
you can go to insidetracker.com/huberman
 
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 means
 
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
 
I eat my carbohydrates,
 
which for me helps me with
 
the transition to sleep
 
and allows me to get great deep sleep.
 
That's what works for me.
 
What that means is in the
 
afternoon I'm craving a snack.
 
And the snack for me is Magic Spoon.
 
What I do lately is I put
 
in some Bulgarian yogurt.
 
Sometimes I just eat it straight.
 
Each serving of Magic Spoon
 
has zero grams of sugar,
 
13 to 14 grams of protein
 
and only four grams of
 
carbohydrates in each serving.
 
So it really matches that
 
low carb ketoish approach.
 
There's only 140 calories per serving,
 
and they have a variety of flavors.
 
Coco, fruity, peanut butter or frosted.
 
I particularly like frosted
 
'cause it tastes like donuts.
 
I try not to eat donuts,
 
but I do love the frost.
 
And as I mentioned before,
 
I lately mix it with yogurt
 
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.
 
=== 00:07:45 “Aging as a Disease” vs. Longevity & Anti-Aging ===
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 you 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.
 
- That clarifies a lot for me, thank you.
 
=== 00:10:23 What Causes Aging? The Epigenome ===
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 together.
 
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 much.
 
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 others.
 
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 thermodynamics.
 
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 this 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 recall.
 
- 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 manifestations
 
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 songs 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 changes in those chemicals.
 
=== 00:15:53 Cosmetic Aging ===
- 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 same 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.
 
=== 00:17:15 Development Never Stops, Horvath Clock ===
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 immense 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 damage,
 
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 aging
 
is massive cell damage or stress.
 
So we pinched nerves and we
 
saw that their aging process
 
was accelerated as well.
 
=== 00:20:12 Puberty Rate as a Determinant of Aging Rate ===
- 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 matured
 
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, Michael 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 their 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.
 
=== 00:23:00 Fasting, Hunger & Food Choices  ===
- 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 not 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 hungry.
 
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 longevity
 
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,
 
but 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.
 
One 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 epigenome.
 
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 component
 
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.
 
- Does 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 tacked
 
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
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