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2022-01-26 - Podcast Dr. David Sinclair - NMN, NR, Resveratrol, Metformin & Other Longevity Molecules: Difference between revisions

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(Created page with "* https://www.youtube.com/watch?v=bRWT7hVgwuM&ab_channel=DavidSinclair * In this week’s episode, Dr. David Sinclair and co-host Matthew LaPlante zero in on drugs and supplem...")
 
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== Transcript ==
== Transcript ==
- Welcome to the Lifespan podcast,
=== Kicking Off Episode Four: Longevity Molecules ===
 
{| class="wikitable"
where we discuss the science of aging
| 0:00
 
| - Welcome to the Lifespan podcast, where we discuss the science of aging and how to be healthier at any stage of life.
and how to be healthier
|-
 
| 0:09
at any stage of life.
| I'm David Sinclair. I'm a professor at Harvard Medical School and Co-director of the Paul F. Glenn Center for Aging Research.
 
|-
I'm David Sinclair.
| 0:16
 
| And I'm joined today by my lovely co-author and cohost, Matthew LaPlante. - Hey, how are we doing? - [David] Hey, welcome.
I'm a professor at Harvard Medical School
|-
 
| 0:23
and Co-director of the Paul F. Glenn
| - Feeling good today. - [Matthew] Back at it again. - We are. We're here today to talk about how to live longer and better.
 
|-
Center for Aging Research.
| 0:29
 
| - As part of this podcast series, this deep dive into things that you can do to slow, stop, and reverse aging.
And I'm joined today
|-
 
| 0:35
by my lovely co-author
| - That is true and today is going to be a really interesting one. - This is going to be the one that everybody,
 
|-
and cohost, Matthew LaPlante.
| 0:41
 
| I mean, this is the one that everybody's been begging for. - That is true. We've been monitoring the responses to tweets
- Hey, how are we doing?
|-
 
| 0:46
- [David] Hey, welcome.
| and Instagram posts, and most of them are, David, just tell us what to take.
 
|-
- Feeling good today.
| 0:52
 
| - [Matthew] The nice ones. - Yeah. - Some of those aren't very nice either, but yeah, please, please, please.
- [Matthew] Back at it again.
|-
 
| 0:57
- We are.
| Should I take NR? Should I take NMN? What should I do with Metformin? We're going to be talking about all of that today.
 
|-
We're here today to talk about
| 1:03
 
| - We are, and our research team has been spending weeks on this, and if you can't see, I'm actually sitting in front of many pages of notes here.
how to live longer and better.
|-
 
| 1:11
- As part of this podcast series,
| We're going to go deep dive into what is fact and what is not fact. What is known, what is not known, because there's so much misinformation out there,
 
|-
this deep dive into things that you can do
| 1:17
 
| especially with supplements. - Yeah. We do need to say we usually take a moment
to slow, stop, and reverse aging.
|-
 
| 1:23
- That is true and today is going
| to thank our sponsors, we're going to do that of course, but we also have to take a moment to say we are not medical doctors. We are not medical doctors.
 
|-
to be a really interesting one.
| 1:30
 
| We are not medical doctors. - What he said. I'm a PhD, I'm a researcher.
- This is going to be
|-
 
| 1:36
the one that everybody,
| I can read the literature. I've been doing it for the last 30 years. I distill that for everybody.
 
|-
I mean, this is the one that
| 1:42
 
| But of course, if you want to try supplement or even change your diet radically, please talk to your physician before you change anything.
everybody's been begging for.
|-
 
| 1:49
- That is true.
| Because some of the things we'll talk about today can affect your body in, hopefully, many good ways, but sometimes can be dangerous depending on the person.
 
|-
We've been monitoring
| 1:57
 
| And everybody's different. - And what we want to do is give people the ability to have a more intelligent
the responses to tweets
|-
 
| 2:02
and Instagram posts, and most of them are,
| and informed conversation with their physician. - Exactly. - Okay, with that out of the way, now we should thank our sponsors.
 
|-
David, just tell us what to take.
| 2:09
 
| - Let's do that, because this podcast is free to anybody who wants to watch or listen.
- [Matthew] The nice ones.
|}
 
=== Thanking the Sponsors ===
- Yeah.
{| class="wikitable"
 
| 2:15
- Some of those aren't very nice either,
| Our first sponsor is Levels. Levels is an app that syncs with a continuous glucose monitor, which they provide,
 
|-
but yeah, please, please, please.
| 2:21
 
| and it interprets your glucose data for you. I've been so impressed by Levels that I've recently joined them as an advisor.
Should I take NR? Should I take NMN?
|-
 
| 2:28
What should I do with Metformin?
| Monitoring your blood glucose allows you to see how different foods impact you. I've used Levels to see what foods impact me.
 
|-
We're going to be talking
| 2:34
 
| I've learned that grapes spike my glucose, white rice, but actually potatoes aren't that bad.
about all of that today.
|-
 
| 2:39
- We are, and our research team has
| It's not just interesting, it's also a lot of fun to see what's going on inside your body.
 
|-
been spending weeks on
| 2:44
 
| So if you'd like to try Levels, you can skip the 150,000 person wait list. And you can join today by going to levels.link/sinclair.
this, and if you can't see,
|-
 
| 2:52
I'm actually sitting in front
| That's levels.link/sinclair. Today's podcast is also brought to us by Inside Tracker.
 
|-
of many pages of notes here.
| 2:58
 
| Inside Tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body
We're going to go deep dive into what
|-
 
| 3:05
is fact and what is not fact.
| and reach your health goals. I've been using Inside Tracker for over a decade and also serve as chair of their advisory board.
 
|-
What is known, what is not known,
| 3:11
 
| I really like Inside Tracker because they make it easy to get your blood test. Either someone can come to your home like they do for me, or we can go to a clinic.
because there's so much
|-
 
| 3:19
misinformation out there,
| They then present the blood analysis in an easy to understand dashboard that provides recommendations for improving your health.
 
|-
especially with supplements.
| 3:25
 
| Their InnerAge 2.0 test, which I helped develop using an AI algorithm, even shows your biological age.
- Yeah.
|-
 
| 3:32
We do need to say we usually take a moment
| If you'd like to try Inside Tracker, you should go visit them at insidetracker.com/sinclair
 
|-
to thank our sponsors, we're
| 3:39
 
| and you'll get 25% off every Inside Tracker plan. Use sinclair as the code at the checkout.
going to do that of course,
|-
 
| 3:46
but we also have to take a moment to say
| Today's episode is also brought to us by Athletic Greens, the all-in-one daily drink to support
 
|-
we are not medical doctors.
| 3:51
 
| better health and peak performance. Athletic Greens is a greens powder developed from a complex blend of 75 vitamins,
We are not medical doctors.
|-
 
| 3:58
We are not medical doctors.
| minerals, and whole foods sourced ingredients. It's filled with adaptogens for calvary, probiotics and digestive enzymes for gut health,
 
|-
- What he said. I'm a
| 4:05
 
| as well as vitamin C and zinc citrate for immune support. I've been drinking Athletic Greens
PhD, I'm a researcher.
|-
 
| 4:11
I can read the literature.
| in the morning for many years and I do that because I don't often eat perfectly and I travel a lot
 
|-
I've been doing it for the last 30 years.
| 4:16
 
| and I can rest assured that I'm getting all the nutrients I need for optimal health.
I distill that for everybody.
|-
 
| 4:22
But of course,
| So if you'd like to try Athletic Greens, you can go to athleticgreens.com/sinclair
 
|-
if you want to try supplement
| 4:27
 
| to claim a special offer. They're giving away five free travel packs, plus a year supply of vitamin D3 for immune support
or even change your diet radically,
|-
 
| 4:34
please talk to your physician
| and vitamin K2 for keeping calcium out of your arteries and putting it where it's needed into your bones.
 
|-
before you change anything.
| 4:40
 
| Again, go to athletic greens.com/sinclair to claim this special offer.
Because some of the things
|}
 
=== An Additional Boost Beyond Adversity Mimetics ===
we'll talk about today
{| class="wikitable"
 
| 4:46
can affect your body in,
| Okay, Matt, let's dive in. There's a lot to get through today and I know everyone's waiting to hear
 
|-
hopefully, many good ways,
| 4:51
 
| what we have to say today. - In the last episode, David, we talked about adversity mimetics. These are the things that we can do in our modern lives
but sometimes can be dangerous
|-
 
| 4:59
depending on the person.
| to mirror the sorts of stresses we faced across our evolutionary history. But even if you're engaged in doing these things
 
|-
And everybody's different.
| 5:07
 
| like we've talked about already, fasting and getting lots of exercise, getting out of your comfort zone,
- And what we want to do is give people
|-
 
| 5:13
the ability to have a more intelligent
| our modern lives are still designed around comfort and sedentariness, is that a word?
 
|-
and informed conversation
| 5:21
 
| - Sedentary lifestyles? - [Matthew] Sedentary lifestyles. And that's not to mention the fact that even before modern times we aged, right?
with their physician.
|-
 
| 5:27
- Exactly.
| So if we're going to combat aging we may need an additional boost.
 
|-
- Okay, with that out of the way,
| 5:32
 
| Do you believe we may need an additional boost? - Well I do and I've been doing this since my early thirties.
now we should thank our sponsors.
|-
 
| 5:37
- Let's do that, because
| We'll talk about my program at the end of this episode, but really what we want to do today
 
|-
this podcast is free
| 5:43
 
| is to talk about some of the major supplements and medicines that are thought and have the greatest
to anybody who wants to watch or listen.
|-
 
| 5:48
Our first sponsor is Levels.
| scientific evidence to be able to give you wellness now as well as long-term health in the future. - Supplements and medicines
 
Levels is an app that syncs
 
with a continuous glucose
 
monitor, which they provide,
 
and it interprets your
 
glucose data for you.
 
I've been so impressed by Levels
 
that I've recently joined
 
them as an advisor.
 
Monitoring your blood glucose allows you
 
to see how different foods impact you.
 
I've used Levels to see
 
what foods impact me.
 
I've learned that grapes spike my glucose,
 
white rice, but actually
 
potatoes aren't that bad.
 
It's not just interesting,
 
it's also a lot of fun to see
 
what's going on inside your body.
 
So if you'd like to try Levels,
 
you can skip the 150,000 person wait list.
 
And you can join today by
 
going to levels.link/sinclair.
 
That's levels.link/sinclair.
 
Today's podcast is also brought
 
to us by Inside Tracker.
 
Inside Tracker is a
 
personalized nutrition platform
 
that analyzes data from your blood and DNA
 
to help you better understand your body
 
and reach your health goals.
 
I've been using Inside
 
Tracker for over a decade
 
and also serve as chair
 
of their advisory board.
 
I really like Inside Tracker because they
 
make it easy to get your blood test.
 
Either someone can come to your home
 
like they do for me, or
 
we can go to a clinic.
 
They then present the blood analysis
 
in an easy to understand dashboard
 
that provides recommendations
 
for improving your health.
 
Their InnerAge 2.0 test,
 
which I helped develop
 
using an AI algorithm,
 
even shows your biological age.
 
If you'd like to try Inside Tracker,
 
you should go visit them at
 
insidetracker.com/sinclair
 
and you'll get 25% off
 
every Inside Tracker plan.
 
Use sinclair as the code at the checkout.
 
Today's episode is also brought
 
to us by Athletic Greens,
 
the all-in-one daily drink to support
 
better health and peak performance.
 
Athletic Greens is a
 
greens powder developed
 
from a complex blend of 75 vitamins,
 
minerals, and whole foods
 
sourced ingredients.
 
It's filled with adaptogens for calvary,
 
probiotics and digestive
 
enzymes for gut health,
 
as well as vitamin C and zinc
 
citrate for immune support.
 
I've been drinking Athletic Greens
 
in the morning for many years
 
and I do that because I don't often
 
eat perfectly and I travel a lot
 
and I can rest assured that I'm getting
 
all the nutrients I
 
need for optimal health.
 
So if you'd like to try Athletic Greens,
 
you can go to athleticgreens.com/sinclair
 
to claim a special offer.
 
They're giving away
 
five free travel packs,
 
plus a year supply of
 
vitamin D3 for immune support
 
and vitamin K2 for keeping
 
calcium out of your arteries
 
and putting it where it's
 
needed into your bones.
 
Again, go to athletic greens.com/sinclair
 
to claim this special offer.
 
Okay, Matt, let's dive in.
 
There's a lot to get through today
 
and I know everyone's waiting to hear
 
what we have to say today.
 
- In the last episode, David,
 
we talked about adversity mimetics.
 
These are the things that we
 
can do in our modern lives
 
to mirror the sorts of stresses
 
we faced across our evolutionary history.
 
But even if you're engaged
 
in doing these things
 
like we've talked about already,
 
fasting and getting lots of exercise,
 
getting out of your comfort zone,
 
our modern lives are still
 
designed around comfort
 
and sedentariness, is that a word?
 
- Sedentary lifestyles?
 
- [Matthew] Sedentary lifestyles.
 
And that's not to mention the fact
 
that even before modern
 
times we aged, right?
 
So if we're going to combat aging
 
we may need an additional boost.
 
Do you believe we may
 
need an additional boost?
 
- Well I do and I've been doing this
 
since my early thirties.
 
We'll talk about my program
 
at the end of this episode,
 
but really what we want to do today
 
is to talk about some
 
of the major supplements
 
and medicines that are
 
thought and have the greatest
 
scientific evidence to be able to give you
 
wellness now as well as
 
long-term health in the future.
 
- Supplements and medicines,
 
drugs and supplements,
 
molecules and drugs.
 
There are a lot of different terms
 
that we're probably going to throw around
 
and we're going to use
 
them fairly synonymously.
 
But in fairness, let's define
 
drug versus supplement, at least.
 
- Right, first of all, most
 
drugs are chemicals, okay?
 
But some are naturally occurring
 
and some are freely available
 
over the counter, OTC.
 
And that's because they've
 
been in our food supply before
 
and the FDA doesn't regulate them.
 
They fall under what's called generally
 
recognized as safe, or GRAS.
 
And that's why you can
 
pick up whole variety
 
of molecules from the plant world,
 
'cause they're already in our food supply.
 
Therefore the government thinks,
 
well, they're probably okay,
 
even if they're a thousand times more
 
concentrated than what you're eating.
 
- Which may or may not be the case, right?
 
- Right, and so that's why
 
you always have to be careful.
 
You have to monitor yourself,
 
like I have been with my blood work
 
for many years to make sure that
 
you're not hurting parts of your body.
 
Your liver particularly could be sensitive
 
to some of these molecules,
 
even if they are available freely
 
at the pharmacy or the vitamin shop.
 
A different story about drugs.
 
Drugs are regulated
 
molecules because they have
 
the chance to actually cause damage.
 
And many drugs actually do
 
have serious side effects
 
that need to be carefully monitored
 
and discussed with the doctor.
 
Even those that are very safe.
 
Like we'll talk about Metformin.
 
These are regulated by the government
 
because they are not in the food supply.
 
There are artificial molecules that
 
could theoretically do damage.
 
- And there are literally
 
thousands of drugs
 
and supplements that someone somewhere
 
will tell you we'll help you
 
with health spans and lifespans.
 
We're not going to talk about
 
thousands of drugs and supplements today.
 
- No, maybe in future
 
episodes we'll come back,
 
but we want to hit the high points today.
 
- And so that's why today we're going
 
to move through some of the most popular
 
and some of the most promising.
 
These are things that most
 
people can have access to,
 
or find a physician who,
 
if the need exists, will prescribe.
 
- Right, and I get emails
 
and I get all sorts of texts
 
every day, DMs, what should I take?
 
What about this? What about that?
 
What's the dose. When should I take it?
 
What should I take it with?
 
Is it okay to take this
 
drug with exercise or not?
 
That's what we're going to cover today.
 
Your most pressing questions
 
answered here today.
 
- And so we're going to
 
talk about NAD boosters.
 
We're going to talk about Metformin,
 
berberine, rapamycin,
 
spermidine, resveratrol,
 
fisetin and quercetin,
 
and probably a few others.
 
But those were sort of
 
the highlight points.
 
If you're only interested in one of these,
 
or if you watch this whole
 
episode need a reminder,
 
the show notes are going to
 
be timestamped so that you can
 
immediately go to berberine
 
and find it and click on it.
 
- That's right, included in the show notes
 
are the scientific references that
 
we now have in front of us
 
that we're going to talk about
 
so that people can do a deep dive,
 
even deeper than what we're
 
going to do here today.
 
- There's one more thing that we'll link
 
to in the show notes
 
that's on your website
 
that I think is valuable
 
for people to know about.
 
You're involved in a lot
 
of different companies.
 
You're an entrepreneur,
 
you're a researcher.
 
You have I don't know how many patents.
 
There are plenty of people who would say,
 
oh, this guy's just trying to sell stuff.
 
If they suspect that you might
 
have a conflict of interest,
 
they can go and look at your disclosures.
 
- I do disclose everything that I do.
 
My lab has a website. You
 
can Google Sinclair Lab.
 
And if you click through my bio,
 
there's a link to all the work
 
that I do outside of Harvard,
 
as well as what we do
 
at Harvard, of course,
 
but importantly, I've never
 
sold any supplement in my life.
 
- And that's not because
 
you're a bad salesman.
 
It's because you haven't
 
actually tried to sell.
 
I mean, there's a difference between
 
having not sold a
 
supplement and having tried
 
to sell a supplement and
 
not sold a supplement.
 
- Right, I've actively kept myself away
 
from the supplement industry
 
because I want to be able
 
to talk about things without any bias.
 
- Not for a lack of opportunity though,
 
there's plenty of people who would
 
love to put your face on a package.
 
- Well, and they do,
 
without my permission.
 
You can see my face on the internet.
 
But if you see that, know that
 
it's not with my permission
 
and I do actively try to stop that.
 
- To get into this let's
 
use some of the same framing
 
that we've used for
 
the other conversation.
 
And that's these three longevity pathways,
 
three longevity genes that
 
we've been talking about.
 
sirtuins, AMPK, and mTOR.
 
Different drugs and
 
supplements are thought
 
to work on these different
 
pathways in different ways.
 
And we'll sort of like categorize them
 
in those three buckets today.
 
- Exactly, and the thing to also remember
 
is that these three survival
 
pathways we've talked about,
 
and in episode one we talked a lot about,
 
are responding to our environment.
 
Whether you're exercising
 
or fasting they'll turn on,
 
but also appreciate that
 
they talk to each other
 
and some drugs or
 
supplements will activate
 
one of these and talk to the other two.
 
So it's a network and we're still
 
trying to figure out exactly
 
what the optimal combination
 
for each individual might be.
 
Whether to tweak it with this molecule
 
and then exercise here
 
and then fast that day.
 
We don't know all the answers,
 
but we are going to present the cutting
 
edge science here today.
 
- And I think it's been
 
really interesting.
 
I've been working with you for, what,
 
like about four years now.
 
And in that time a lot of the molecules
 
that we knew to be working
 
on one of these pathways,
 
there's been further
 
research that has said,
 
oh, that's not just an AMPK effect.
 
There's also an mTOR connection there.
 
- Well they definitely talk to each other.
 
Because if you're low on immuno acids
 
and it'll turn on the
 
mTOR protection pathway,
 
that will then tell the other survival
 
pathways to do their thing too.
 
It's like the Pentagon where
 
there's centrally coordinated defenses
 
and basically what we're trying to do
 
is to make prank phone
 
call to the Pentagon to say
 
there's an emergency and
 
they'll send out the troops
 
in various ways and protect the body,
 
even though there's no immediate threat.
 
- I like that analogy. That's fun.
 
Let's talk about the class of molecules
 
that you've worked most
 
extensively on in your lab.
 
These are known as NAD boosters.
 
Talk a little bit about why
 
NAD is important in our bodies.
 
It's really important, if it disappears,
 
we're screwed, right?
 
- Well, we'd be dead in 30 seconds.
 
We need it for energy
 
but it was discovered
 
about 100 years ago by Germans
 
who were looking at extracts in yeast.
 
And there was this component called NAD
 
that was necessary for chemical reactions.
 
- We didn't say what
 
that stands for, that's?
 
- So NAD stands for nicotinamide,
 
which is vitamin B3,
 
and adenine dinucleotide. This
 
is a sugar and a phosphate.
 
The important part about
 
it is that our cells
 
use NAD to transfer hydrogen atoms
 
between proteins and even DNA.
 
That is really important
 
for life and without it
 
we can't make chemical energy,
 
which is in the form of ATP,
 
which we'll talk about later
 
because that's important for Metformin.
 
NAD is found in abundance.
 
There's many grams of it in the body.
 
It's probably, with the exception of ATP,
 
the most abundant molecule
 
we have in the body.
 
It helps us make energy but it
 
also has this other function
 
that's just as important
 
that we worked on and just
 
co-discovered in the 2000s.
 
It activates the sirtuins
 
and the sirtuins are these
 
defensive enzymes that, like the Pentagon,
 
send out the troops.
 
The problem is as we get
 
older we make less NAD
 
and we also destroy it more for reasons
 
that we don't fully understand,
 
but it leads to a decline in our ability
 
to fight off aging and the
 
diseases that it causes.
 
- And this is because NAD
 
is a sensor for adversity.
 
- It is, if you exercise, it's known,
 
and fast, it's known to raise NAD levels.
 
But even if you exercise and
 
have the healthiest diet,
 
you're still going to have
 
lower NAD levels by the time,
 
you know, you're in the
 
latter half of your life.
 
So that's why these
 
supplements are thought to help
 
because they'll boost up
 
those older levels of NAD
 
to where they were when you were young.
 
- Okay. So let's talk about
 
the first NAD booster.
 
Probably the most well-known,
 
it's definitely the most well
 
studied of the NAD boosters,
 
and probably the most
 
taken used. That's NR.
 
- Which stands for nicotinamide riboside.
 
So that's the vitamin B3 plus the sugar.
 
Without the N part, which is a phosphate,
 
we'll get to the phosphate,
 
that's important later.
 
It may make a difference,
 
but NR has been taken over the counter
 
or through websites for, what, since 2014,
 
either solely just as a capsule
 
or there's some companies that sell it
 
in combination with other molecules.
 
- And because it's been
 
pretty well studied in humans,
 
there've been plenty of human studies,
 
at least in the short term that show
 
little to no side effects.
 
This is a pretty safe molecule.
 
- That's for sure.
 
We know that if you
 
take it as a supplement
 
to swallow the pill, either 250 milligrams
 
per day or a gram, there's
 
no apparent negative side
 
effects, and in fact, you will raise
 
NAD levels in blood tests.
 
- So I think this is an
 
important distinction to make,
 
though, like there's a difference between
 
safe and effective, right?
 
Just because we say something as safe,
 
doesn't mean it's going to work enough.
 
And in fact sometimes things
 
that are the most safe
 
aren't going to work at all.
 
That's why they're so safe is
 
they don't have any effect.
 
But we do know that NR is
 
largely safe, you know,
 
millions of people
 
around the world take it.
 
NRs have been well studied
 
in animals as well.
 
And let's start with that
 
because we actually know more
 
about what NR does in
 
the bodies of animals
 
than we do in the bodies of humans.
 
- Well let's start with
 
yeast. Go even further back.
 
- Okay, yeah.
 
- So that's where it was first discovered.
 
NR was a newly discovered
 
molecule back in the early 2000s.
 
It's found a little bit in
 
milk and other food selves.
 
And if it was fed to yeast,
 
they lived longer by turning
 
on the yeast sirtuin pathway.
 
- Okay. How much longer
 
were the yeast living?
 
- Generally yeast live about 30% longer
 
when you give them these molecules,
 
similar to choleric restriction.
 
And that's what this was doing,
 
mimicking choleric restriction,
 
'cause both activate the sirtuins
 
and give increased genome stability
 
and epigenome stability
 
that lengthens their life.
 
- And those kinds of findings
 
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