November 28, 2025 • 11 mins
A clear look at anti-aging supplements—NAD, NR, NMN, rapamycin, berberine—versus the proven longevity levers: sleep, training, nutrition, and light.
In this episode, we dissect the anti-aging supplement boom and separate hype from what actually holds up in humans. We revisit resveratrol’s limitations in real-world data and how its role has shifted toward vascular support. Then we break down NAD-boosting strategies, including NR (which reliably raises NAD), NMN’s uncertain status, and the regulatory changes that complicate access. We also discuss the difference between subjective energy boosts and root-cause improvements—and why NAD IVs often function more like expensive, uncomfortable “reboots” than long-term solutions.
We evaluate berberine and metformin, outlining their benefits, drawbacks, and the exercise trade-offs often overlooked. We then tackle rapamycin, reviewing its mechanistic promise alongside side effects and why most people should wait before experimenting with mTOR-targeting drugs.
From there, we contrast supplements with the foundational longevity levers that consistently deliver in humans: high-quality sleep, structured exercise (zone 2, VO2 max, strength), nutrition built around whole foods, stress management, social connection, and morning light.
Throughout the episode, we emphasize the importance of physician guidance before adding or removing any drug or supplement.
Listener Takeaways:
• Why most anti-aging supplements don’t live up to the hype
• NAD strategies: NR, NMN uncertainty, and NAD IV trade-offs
• Berberine & metformin benefits and drawbacks
• Rapamycin promise vs. real-world risks
• The proven longevity levers that outperform supplements
Follow for daily longevity and wellness episodes.
Please consult a board-certified physician before you add or remove anything from your regimen.
This podcast is created by Ai for educational and entertainment purposes only and does not constitute professional medical or health advice. Please talk to your healthcare team for medical advice.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
SPEAKER_01 (00:00):
Welcome to the deep dive.
Today we're putting on ourskeptical glasses and uh
venturing into the$60 billionanti-aging industry.
SPEAKER_02 (00:09):
Yeah.
And our mission here is prettysimple, but it's also really
crucial.
SPEAKER_01 (00:13):
Aaron Powell We're trying to cut through all the
noise, right?
Separate the scientific factfrom well, the internet hype
when it comes to these reallypopular longevity supplements.
SPEAKER_02 (00:22):
Aaron Powell That's it exactly.
We're diving into sources thatlook at compounds like
resveratrol, NR, and NMN,metformin, and rapamycin.
SPEAKER_01 (00:31):
Okay.
SPEAKER_02 (00:32):
And we really need to contrast what the actual
scientific data shows, you know,for increasing lifespan with the
effects people feel when theytake this stuff.
SPEAKER_01 (00:41):
Aaron Powell Which can be really powerful
subjectively.
And I think if we're going togive you the main takeaway right
at the top, it's this.
SPEAKER_02 (00:47):
Go on.
SPEAKER_01 (00:47):
A lot of these supplements that get all the
attention and cost a fortune,they currently lack strong
direct evidence in humans foractually making you live longer.
SPEAKER_02 (00:56):
Right.
And yet people are spendingserious money on them, so we
have to figure out why we'reanalyzing that trade-off.
SPEAKER_01 (01:01):
Aaron Powell So people can understand the
science, which often says wedon't know yet, versus the
feeling, which might be I feelgreat right now.
SPEAKER_02 (01:08):
Precisely.
SPEAKER_01 (01:09):
All right.
So let's start with the one thatI feel like really kicked off
this whole modern conversation,resveratrol.
SPEAKER_02 (01:14):
Oh yeah, the compound from grapes and red
wine.
A couple of decades ago, theexcitement was, I mean, it was
enormous.
SPEAKER_01 (01:22):
The theory was that it could activate these key
cellular pathways, right?
The sortium.
SPEAKER_02 (01:26):
Exactly.
And it seemed to extend thelifespan of like yeast and
worms.
Everyone thought, this is it.
We found the first reallongevity pill.
SPEAKER_01 (01:35):
It's amazing how quickly that whole narrative
just kind of fell apart.
SPEAKER_02 (01:38):
It really is.
And the core issue wasn't thescience in the Pitri dish, it
was the delivery mechanism inhumans.
The current consensus as of 2023is that the whole longevity idea
for resveratrol has been prettymuch uh debunked.
SPEAKER_01 (01:52):
Debunked.
Why though?
If it worked in simpleorganisms, why not in us?
SPEAKER_02 (01:57):
It all comes down to bioavailability.
In humans, resmeratrol is justabsorbed very, very poorly.
SPEAKER_01 (02:02):
So your body breaks it down almost instantly.
SPEAKER_02 (02:04):
Almost instantly.
To get the concentrations you'dneed to actually flip those
sertuan switches in your cells,you'd have to take doses so high
they'd be impractical andprobably toxic.
SPEAKER_01 (02:14):
So a dead end for lifespan.
SPEAKER_02 (02:16):
Okay.
SPEAKER_01 (02:17):
But people are still taking related stuff like
grapeseed extract.
What's the thinking there?
SPEAKER_02 (02:22):
Right.
So the longevity angle is gone,but grapeseed extract, which has
resveratrol or molecules thatconvert to it, it still has some
use.
The focus is just completelyshifted.
SPEAKER_01 (02:33):
Shifted to what?
SPEAKER_02 (02:34):
To vascular function and blood flow.
When you see people taking, say,400 to 800 milligrams of it
daily, that's what they're doingit for.
SPEAKER_01 (02:42):
So you're not taking it to add years, but to make
sure your internal plumbing,your blood vessels are working
well.
SPEAKER_02 (02:48):
Exactly.
It's more of an insurance policyfor your circulation, not some
anti-aging miracle.
And that's why, you know, whileit's safe, it wouldn't even
crack the top 10 list ofsupplements for overall health
impact.
SPEAKER_01 (02:58):
Got it.
Okay, let's shift gears to thebig one from the last few years,
the NAD pathway.
SPEAKER_02 (03:04):
Nicotinamide, adenine dinucleotide.
Yes, this has dominated theconversation for about five
years now.
SPEAKER_01 (03:10):
And unlike resveratrol, the importance of
NAD itself isn't really up fordebate.
SPEAKER_02 (03:15):
No, it's fundamental.
NAD is crucial for cellularenergy.
It's like the currency of yourmitochondria.
It's super active when we'reyoung, but the levels just taper
off as we age.
SPEAKER_01 (03:26):
Which creates an energy deficit in our cells.
So the goal is to boost thoselevels back up with supplements.
SPEAKER_02 (03:31):
Right.
And the two main ones you hearabout are NR, nicotinamide
riboside, and NMN, nicotinamidemononucleotide.
SPEAKER_00 (03:39):
And this is where the debate starts.
Tell us about the issues withthose two.
SPEAKER_02 (03:43):
Well, NR is pretty well accepted to increase NAD
levels.
You take it as a pill or powder,pretty straightforward.
NMN is way more contentious.
SPEAKER_01 (03:52):
Why is that?
SPEAKER_02 (03:53):
There's a big debate about whether it can even get
into cells efficiently to beconverted into NAD, and then the
story gets even morecomplicated.
SPEAKER_01 (03:59):
Ah, with the FDA ruling.
SPEAKER_02 (04:01):
Crucially, yes.
In 2023, the FDA ruled thatbecause NMN was filed as an
experimental drug for a clinicaltrial, it can't legally be sold
as a dietary supplement anymore.
SPEAKER_01 (04:11):
So it's sort of in this gray market now.
SPEAKER_02 (04:13):
Aaron Ross Powell Exactly.
Which adds a whole other layerof ambiguity.
But people are still takingthese things daily.
SPEAKER_01 (04:18):
Aaron Powell But if the long-term benefit for
lifespan is, as you said,somewhat unlikely for humans,
why are they so committed to it?
SPEAKER_02 (04:26):
It comes down almost entirely to the subjective
feeling.
This is where the cost-benefitanalysis gets really personal.
SPEAKER_01 (04:31):
What's the protocol and what's the feeling?
SPEAKER_02 (04:33):
People will take something like 500 milligrams of
NMR, maybe one to two grams ofsublingual NMN every day.
And the benefit they report isthis tangible feeling of uh
sustained mental and physicalenergy.
SPEAKER_01 (04:48):
A boost to vigor.
SPEAKER_02 (04:49):
A real boost.
And they often say they notice aclear decrement in energy if
they stop.
It's a powerful, acute effect.
SPEAKER_01 (04:56):
Aaron Powell, but couldn't that just be masking
something else like poor sleep?
SPEAKER_02 (04:59):
That's the critical question you have to ask.
Are you paying a lot of money topaper over a foundational
problem?
For some, the boost is sosignificant, they prioritize
that feeling of quality of lifenow over an uncertain longevity
benefit way down the road.
SPEAKER_01 (05:13):
Aaron Powell Which leads us to the most extreme
version of this.
SPEAKER_02 (05:16):
The most direct and definitely the most challenging
way to boost NAD, intravenousinfusion.
SPEAKER_01 (05:23):
Right, getting it put directly into your veins.
This sounds way more intensethan just taking a pill.
SPEAKER_02 (05:28):
Oh, it is.
It's significantlyuncomfortable.
We're talking high doses, 500 to1,000 milligrams of NAD dripped
in over an hour or more.
SPEAKER_01 (05:37):
And because it's such a powerful metabolic
signal, just slamming it intoyour bloodstream causes side
effects.
SPEAKER_02 (05:44):
Intense side effects.
The experience is notoriouslydifficult.
Many clinics will even give youanti-nause medication
beforehand.
SPEAKER_01 (05:51):
What does it actually feel like?
SPEAKER_02 (05:52):
People report this really unsettling physical
pressure, almost like someone isstepping on your chest and legs.
It's a systemic flush.
SPEAKER_01 (05:59):
Wow.
SPEAKER_02 (05:59):
Now that part usually only lasts about 10
minutes, but it can be genuinelyalarming.
SPEAKER_01 (06:04):
And people endure that for a benefit that isn't
even proven to extend theirlife.
SPEAKER_02 (06:08):
They do.
And the rationale is purelyabout acute functional
improvement.
SPEAKER_01 (06:12):
Like a reboot.
SPEAKER_02 (06:13):
Exactly.
Especially if you're feeling rundown or jet-legged, users report
feeling much, much betterafterwards.
Improved sleep, more vigor.
It's used as a very expensive,inconvenient, and uncomfortable
reboot button.
SPEAKER_00 (06:27):
Maybe a few times a year.
SPEAKER_02 (06:28):
At most.
And we have to be clear.
Whether this actually translatesto a longer life is hotly
debated by the top scientists inthe field.
People like Charles Brunner,David Sinclair, Matt Caberlin.
They are not all in agreement onthis.
SPEAKER_01 (06:40):
Aaron Powell Okay, so if the NAB pathway is about
energy, let's talk about thepathway that's all about growth.
MTO.
This feels like a shift intomore serious pharmaceutical
grade stuff.
SPEAKER_02 (06:52):
Aaron Powell It's a critical distinction, yeah.
MTR stands for mammalian targetof rapamycin.
It's a core pathway that governscell growth.
SPEAKER_01 (06:59):
Aaron Powell It's good when you're a kid, but
maybe not so good later in life.
SPEAKER_02 (07:03):
That's the theory.
That by reducing this growthsignal in later life, you can
sort of switch the body into amaintenance and repair mode,
which could increase lifespan.
SPEAKER_01 (07:10):
Aaron Powell And people try to do this with
things like berberine first.
SPEAKER_02 (07:13):
Right.
Berberine is a natural compound.
People call it the poor man'smetformin because it lowers
blood glucose.
But a lot of people stop takingit because of the side effects.
SPEAKER_01 (07:22):
Like what?
SPEAKER_02 (07:23):
GI issues, for one.
And for some, the blood glucoselowering can cause these uh
brutal headaches.
SPEAKER_01 (07:29):
Aaron Powell So then there's metformin itself, the
actual diabetes drug.
Why are experts still hesitantto recommend it for just anyone
trying to live longer?
SPEAKER_02 (07:38):
Well, while it works wonders in some animal models,
and of course for people withtype 2 diabetes, the data for a
healthy person is stillinconclusive.
SPEAKER_01 (07:47):
And there's a downside with exercise, right?
SPEAKER_02 (07:48):
There is.
There's evidence it can actuallyblunt the positive adaptations
you get from exercise.
So right now, the expertconsensus is that there just
isn't enough data to supporttaking it purely for longevity.
SPEAKER_01 (08:01):
Which brings us to the compound the pathway is
named for rapamycin.
SPEAKER_02 (08:05):
This is where the most focused research is
happening right now.
Dr.
Matt Caberline's big dog agestudy is a perfect example.
They're testing it directly.
SPEAKER_01 (08:12):
But despite all that research excitement, our sources
show it's still avoided forpersonal use.
The risk reward just isn't thereyet.
SPEAKER_02 (08:21):
Not for most people.
The side effect profile issignificant.
I mean, it's animmunosuppressant.
SPEAKER_01 (08:25):
Used to prevent organ rejection in transplant
patients.
SPEAKER_02 (08:28):
Right.
So taking it means suppressingyour immune system.
That's a huge risk.
Plus, you can get mouth sores,GI issues, changes in your
cholesterol.
SPEAKER_01 (08:36):
So when you weigh a totally unproven longevity game
against those kinds of realsubstantiated risks.
SPEAKER_02 (08:42):
The advice from almost every expert is to be
cautious and wait for much, muchmore human data.
SPEAKER_01 (08:48):
Aaron Powell You know, this is the point where we
have to step back.
Because after all this talkabout pills and infusions, we
have to land on the insight weget from every single credible
expert we look at, people likeDr.
Peter Adia.
SPEAKER_02 (09:00):
We absolutely do.
And it's this no pill, no drug,no infusion even comes close to
the known benefits you get fromfoundational lifestyle
practices.
SPEAKER_01 (09:08):
Aaron Powell This is the essential truth, isn't it?
That supplements are at bestsecondary.
SPEAKER_02 (09:13):
Strictly secondary.
Trying to use supplements whileignoring the basics is like it's
like trying to paint a housethat's being eaten by termites.
You have to fix the foundationfirst.
SPEAKER_01 (09:23):
Okay, so let's detail that foundation.
Pillar number one sleep.
SPEAKER_02 (09:27):
Non-negotiable.
Getting enough high-qualitysleep every night is paramount.
We know for a fact that notdoing so measurably reduces your
lifespan.
It has to be priority one.
SPEAKER_01 (09:39):
And pillar number two, which needs to be really
specific, exercise.
And we're not just talking abouta casual walk.
SPEAKER_02 (09:46):
No, this is the highest leverage thing you can
do.
The data points to a minimum of180 to 220 minutes of zone two
cardio per week.
SPEAKER_01 (09:54):
So that's about three to four hours where you
can still talk, but you don'treally want to.
That barely breathless feeling.
SPEAKER_02 (09:59):
Exactly.
That's the minimum to move theneedle.
And you also need highintensity, VO2 max work at least
once a week where you're pushingyour heart rate way up.
SPEAKER_01 (10:07):
And what about strength training?
SPEAKER_02 (10:09):
Just as crucial.
You need resistance training.
A minimum of six hard sets perbody part per week.
This is about fighting offmuscle loss and protecting you
from falls later in life.
SPEAKER_01 (10:19):
So sleep and very specific exercise are mandatory.
What else is on thatfoundational list?
SPEAKER_02 (10:25):
Quality nutrition, managing your stress, having
real social connection, andgetting morning sunlight to set
your circadian rhythm.
These things have an outsizedproven effect that no pill we've
talked about can touch.
SPEAKER_01 (10:38):
And let's just hammer home our safety warning
one more time.
SPEAKER_02 (10:41):
Please.
Because we talked about drugslike metformin and rapamycin,
you absolutely have to consult aboard-certified physician before
you add or remove anything fromyour regimen.
SPEAKER_00 (10:50):
Absolutely.
SPEAKER_02 (10:51):
So just to recap the nuggets we pulled today,
resveratrol's real value now isfor vascular support, not
lifespan.
SPEAKER_01 (10:57):
Right.
NAD supplements give asubjective energy boost, but the
human longevity data just isn'tthere yet.
SPEAKER_02 (11:03):
And the MTOR inhibitors like rapamycin are
still too risky for general useuntil we have a lot more data.
SPEAKER_01 (11:09):
Which leaves you, the listener, with a final
thought to mull over.
If exercise and sleep aredemonstrably the most powerful
longevity drugs we currentlyknow, and science really does
say they are, how would yourapproach change if you shifted
your focus and your budget tomaximizing those things?
SPEAKER_02 (11:26):
That's the question.
If you treated your sleep andyour gym time with the same
commitment you'd give to anexpensive experimental pill,
what kind of longevity dividendwould you be paying yourself
right now?
SPEAKER_01 (11:39):
Think about that.
Are you truly maximizing yournon negotiable health
foundations before you eventhink about reaching for that
supplement stack?
Welcome to the deep dive.
Today we're putting on ourskeptical glasses and uh
venturing into the$60 billionanti-aging industry.
SPEAKER_02 (00:09):
Yeah.
And our mission here is prettysimple, but it's also really
crucial.
SPEAKER_01 (00:13):
Aaron Powell We're trying to cut through all the
noise, right?
Separate the scientific factfrom well, the internet hype
when it comes to these reallypopular longevity supplements.
SPEAKER_02 (00:22):
Aaron Powell That's it exactly.
We're diving into sources thatlook at compounds like
resveratrol, NR, and NMN,metformin, and rapamycin.
SPEAKER_01 (00:31):
Okay.
SPEAKER_02 (00:32):
And we really need to contrast what the actual
scientific data shows, you know,for increasing lifespan with the
effects people feel when theytake this stuff.
SPEAKER_01 (00:41):
Aaron Powell Which can be really powerful
subjectively.
And I think if we're going togive you the main takeaway right
at the top, it's this.
SPEAKER_02 (00:47):
Go on.
SPEAKER_01 (00:47):
A lot of these supplements that get all the
attention and cost a fortune,they currently lack strong
direct evidence in humans foractually making you live longer.
SPEAKER_02 (00:56):
Right.
And yet people are spendingserious money on them, so we
have to figure out why we'reanalyzing that trade-off.
SPEAKER_01 (01:01):
Aaron Powell So people can understand the
science, which often says wedon't know yet, versus the
feeling, which might be I feelgreat right now.
SPEAKER_02 (01:08):
Precisely.
SPEAKER_01 (01:09):
All right.
So let's start with the one thatI feel like really kicked off
this whole modern conversation,resveratrol.
SPEAKER_02 (01:14):
Oh yeah, the compound from grapes and red
wine.
A couple of decades ago, theexcitement was, I mean, it was
enormous.
SPEAKER_01 (01:22):
The theory was that it could activate these key
cellular pathways, right?
The sortium.
SPEAKER_02 (01:26):
Exactly.
And it seemed to extend thelifespan of like yeast and
worms.
Everyone thought, this is it.
We found the first reallongevity pill.
SPEAKER_01 (01:35):
It's amazing how quickly that whole narrative
just kind of fell apart.
SPEAKER_02 (01:38):
It really is.
And the core issue wasn't thescience in the Pitri dish, it
was the delivery mechanism inhumans.
The current consensus as of 2023is that the whole longevity idea
for resveratrol has been prettymuch uh debunked.
SPEAKER_01 (01:52):
Debunked.
Why though?
If it worked in simpleorganisms, why not in us?
SPEAKER_02 (01:57):
It all comes down to bioavailability.
In humans, resmeratrol is justabsorbed very, very poorly.
SPEAKER_01 (02:02):
So your body breaks it down almost instantly.
SPEAKER_02 (02:04):
Almost instantly.
To get the concentrations you'dneed to actually flip those
sertuan switches in your cells,you'd have to take doses so high
they'd be impractical andprobably toxic.
SPEAKER_01 (02:14):
So a dead end for lifespan.
SPEAKER_02 (02:16):
Okay.
SPEAKER_01 (02:17):
But people are still taking related stuff like
grapeseed extract.
What's the thinking there?
SPEAKER_02 (02:22):
Right.
So the longevity angle is gone,but grapeseed extract, which has
resveratrol or molecules thatconvert to it, it still has some
use.
The focus is just completelyshifted.
SPEAKER_01 (02:33):
Shifted to what?
SPEAKER_02 (02:34):
To vascular function and blood flow.
When you see people taking, say,400 to 800 milligrams of it
daily, that's what they're doingit for.
SPEAKER_01 (02:42):
So you're not taking it to add years, but to make
sure your internal plumbing,your blood vessels are working
well.
SPEAKER_02 (02:48):
Exactly.
It's more of an insurance policyfor your circulation, not some
anti-aging miracle.
And that's why, you know, whileit's safe, it wouldn't even
crack the top 10 list ofsupplements for overall health
impact.
SPEAKER_01 (02:58):
Got it.
Okay, let's shift gears to thebig one from the last few years,
the NAD pathway.
SPEAKER_02 (03:04):
Nicotinamide, adenine dinucleotide.
Yes, this has dominated theconversation for about five
years now.
SPEAKER_01 (03:10):
And unlike resveratrol, the importance of
NAD itself isn't really up fordebate.
SPEAKER_02 (03:15):
No, it's fundamental.
NAD is crucial for cellularenergy.
It's like the currency of yourmitochondria.
It's super active when we'reyoung, but the levels just taper
off as we age.
SPEAKER_01 (03:26):
Which creates an energy deficit in our cells.
So the goal is to boost thoselevels back up with supplements.
SPEAKER_02 (03:31):
Right.
And the two main ones you hearabout are NR, nicotinamide
riboside, and NMN, nicotinamidemononucleotide.
SPEAKER_00 (03:39):
And this is where the debate starts.
Tell us about the issues withthose two.
SPEAKER_02 (03:43):
Well, NR is pretty well accepted to increase NAD
levels.
You take it as a pill or powder,pretty straightforward.
NMN is way more contentious.
SPEAKER_01 (03:52):
Why is that?
SPEAKER_02 (03:53):
There's a big debate about whether it can even get
into cells efficiently to beconverted into NAD, and then the
story gets even morecomplicated.
SPEAKER_01 (03:59):
Ah, with the FDA ruling.
SPEAKER_02 (04:01):
Crucially, yes.
In 2023, the FDA ruled thatbecause NMN was filed as an
experimental drug for a clinicaltrial, it can't legally be sold
as a dietary supplement anymore.
SPEAKER_01 (04:11):
So it's sort of in this gray market now.
SPEAKER_02 (04:13):
Aaron Ross Powell Exactly.
Which adds a whole other layerof ambiguity.
But people are still takingthese things daily.
SPEAKER_01 (04:18):
Aaron Powell But if the long-term benefit for
lifespan is, as you said,somewhat unlikely for humans,
why are they so committed to it?
SPEAKER_02 (04:26):
It comes down almost entirely to the subjective
feeling.
This is where the cost-benefitanalysis gets really personal.
SPEAKER_01 (04:31):
What's the protocol and what's the feeling?
SPEAKER_02 (04:33):
People will take something like 500 milligrams of
NMR, maybe one to two grams ofsublingual NMN every day.
And the benefit they report isthis tangible feeling of uh
sustained mental and physicalenergy.
SPEAKER_01 (04:48):
A boost to vigor.
SPEAKER_02 (04:49):
A real boost.
And they often say they notice aclear decrement in energy if
they stop.
It's a powerful, acute effect.
SPEAKER_01 (04:56):
Aaron Powell, but couldn't that just be masking
something else like poor sleep?
SPEAKER_02 (04:59):
That's the critical question you have to ask.
Are you paying a lot of money topaper over a foundational
problem?
For some, the boost is sosignificant, they prioritize
that feeling of quality of lifenow over an uncertain longevity
benefit way down the road.
SPEAKER_01 (05:13):
Aaron Powell Which leads us to the most extreme
version of this.
SPEAKER_02 (05:16):
The most direct and definitely the most challenging
way to boost NAD, intravenousinfusion.
SPEAKER_01 (05:23):
Right, getting it put directly into your veins.
This sounds way more intensethan just taking a pill.
SPEAKER_02 (05:28):
Oh, it is.
It's significantlyuncomfortable.
We're talking high doses, 500 to1,000 milligrams of NAD dripped
in over an hour or more.
SPEAKER_01 (05:37):
And because it's such a powerful metabolic
signal, just slamming it intoyour bloodstream causes side
effects.
SPEAKER_02 (05:44):
Intense side effects.
The experience is notoriouslydifficult.
Many clinics will even give youanti-nause medication
beforehand.
SPEAKER_01 (05:51):
What does it actually feel like?
SPEAKER_02 (05:52):
People report this really unsettling physical
pressure, almost like someone isstepping on your chest and legs.
It's a systemic flush.
SPEAKER_01 (05:59):
Wow.
SPEAKER_02 (05:59):
Now that part usually only lasts about 10
minutes, but it can be genuinelyalarming.
SPEAKER_01 (06:04):
And people endure that for a benefit that isn't
even proven to extend theirlife.
SPEAKER_02 (06:08):
They do.
And the rationale is purelyabout acute functional
improvement.
SPEAKER_01 (06:12):
Like a reboot.
SPEAKER_02 (06:13):
Exactly.
Especially if you're feeling rundown or jet-legged, users report
feeling much, much betterafterwards.
Improved sleep, more vigor.
It's used as a very expensive,inconvenient, and uncomfortable
reboot button.
SPEAKER_00 (06:27):
Maybe a few times a year.
SPEAKER_02 (06:28):
At most.
And we have to be clear.
Whether this actually translatesto a longer life is hotly
debated by the top scientists inthe field.
People like Charles Brunner,David Sinclair, Matt Caberlin.
They are not all in agreement onthis.
SPEAKER_01 (06:40):
Aaron Powell Okay, so if the NAB pathway is about
energy, let's talk about thepathway that's all about growth.
MTO.
This feels like a shift intomore serious pharmaceutical
grade stuff.
SPEAKER_02 (06:52):
Aaron Powell It's a critical distinction, yeah.
MTR stands for mammalian targetof rapamycin.
It's a core pathway that governscell growth.
SPEAKER_01 (06:59):
Aaron Powell It's good when you're a kid, but
maybe not so good later in life.
SPEAKER_02 (07:03):
That's the theory.
That by reducing this growthsignal in later life, you can
sort of switch the body into amaintenance and repair mode,
which could increase lifespan.
SPEAKER_01 (07:10):
Aaron Powell And people try to do this with
things like berberine first.
SPEAKER_02 (07:13):
Right.
Berberine is a natural compound.
People call it the poor man'smetformin because it lowers
blood glucose.
But a lot of people stop takingit because of the side effects.
SPEAKER_01 (07:22):
Like what?
SPEAKER_02 (07:23):
GI issues, for one.
And for some, the blood glucoselowering can cause these uh
brutal headaches.
SPEAKER_01 (07:29):
Aaron Powell So then there's metformin itself, the
actual diabetes drug.
Why are experts still hesitantto recommend it for just anyone
trying to live longer?
SPEAKER_02 (07:38):
Well, while it works wonders in some animal models,
and of course for people withtype 2 diabetes, the data for a
healthy person is stillinconclusive.
SPEAKER_01 (07:47):
And there's a downside with exercise, right?
SPEAKER_02 (07:48):
There is.
There's evidence it can actuallyblunt the positive adaptations
you get from exercise.
So right now, the expertconsensus is that there just
isn't enough data to supporttaking it purely for longevity.
SPEAKER_01 (08:01):
Which brings us to the compound the pathway is
named for rapamycin.
SPEAKER_02 (08:05):
This is where the most focused research is
happening right now.
Dr.
Matt Caberline's big dog agestudy is a perfect example.
They're testing it directly.
SPEAKER_01 (08:12):
But despite all that research excitement, our sources
show it's still avoided forpersonal use.
The risk reward just isn't thereyet.
SPEAKER_02 (08:21):
Not for most people.
The side effect profile issignificant.
I mean, it's animmunosuppressant.
SPEAKER_01 (08:25):
Used to prevent organ rejection in transplant
patients.
SPEAKER_02 (08:28):
Right.
So taking it means suppressingyour immune system.
That's a huge risk.
Plus, you can get mouth sores,GI issues, changes in your
cholesterol.
SPEAKER_01 (08:36):
So when you weigh a totally unproven longevity game
against those kinds of realsubstantiated risks.
SPEAKER_02 (08:42):
The advice from almost every expert is to be
cautious and wait for much, muchmore human data.
SPEAKER_01 (08:48):
Aaron Powell You know, this is the point where we
have to step back.
Because after all this talkabout pills and infusions, we
have to land on the insight weget from every single credible
expert we look at, people likeDr.
Peter Adia.
SPEAKER_02 (09:00):
We absolutely do.
And it's this no pill, no drug,no infusion even comes close to
the known benefits you get fromfoundational lifestyle
practices.
SPEAKER_01 (09:08):
Aaron Powell This is the essential truth, isn't it?
That supplements are at bestsecondary.
SPEAKER_02 (09:13):
Strictly secondary.
Trying to use supplements whileignoring the basics is like it's
like trying to paint a housethat's being eaten by termites.
You have to fix the foundationfirst.
SPEAKER_01 (09:23):
Okay, so let's detail that foundation.
Pillar number one sleep.
SPEAKER_02 (09:27):
Non-negotiable.
Getting enough high-qualitysleep every night is paramount.
We know for a fact that notdoing so measurably reduces your
lifespan.
It has to be priority one.
SPEAKER_01 (09:39):
And pillar number two, which needs to be really
specific, exercise.
And we're not just talking abouta casual walk.
SPEAKER_02 (09:46):
No, this is the highest leverage thing you can
do.
The data points to a minimum of180 to 220 minutes of zone two
cardio per week.
SPEAKER_01 (09:54):
So that's about three to four hours where you
can still talk, but you don'treally want to.
That barely breathless feeling.
SPEAKER_02 (09:59):
Exactly.
That's the minimum to move theneedle.
And you also need highintensity, VO2 max work at least
once a week where you're pushingyour heart rate way up.
SPEAKER_01 (10:07):
And what about strength training?
SPEAKER_02 (10:09):
Just as crucial.
You need resistance training.
A minimum of six hard sets perbody part per week.
This is about fighting offmuscle loss and protecting you
from falls later in life.
SPEAKER_01 (10:19):
So sleep and very specific exercise are mandatory.
What else is on thatfoundational list?
SPEAKER_02 (10:25):
Quality nutrition, managing your stress, having
real social connection, andgetting morning sunlight to set
your circadian rhythm.
These things have an outsizedproven effect that no pill we've
talked about can touch.
SPEAKER_01 (10:38):
And let's just hammer home our safety warning
one more time.
SPEAKER_02 (10:41):
Please.
Because we talked about drugslike metformin and rapamycin,
you absolutely have to consult aboard-certified physician before
you add or remove anything fromyour regimen.
SPEAKER_00 (10:50):
Absolutely.
SPEAKER_02 (10:51):
So just to recap the nuggets we pulled today,
resveratrol's real value now isfor vascular support, not
lifespan.
SPEAKER_01 (10:57):
Right.
NAD supplements give asubjective energy boost, but the
human longevity data just isn'tthere yet.
SPEAKER_02 (11:03):
And the MTOR inhibitors like rapamycin are
still too risky for general useuntil we have a lot more data.
SPEAKER_01 (11:09):
Which leaves you, the listener, with a final
thought to mull over.
If exercise and sleep aredemonstrably the most powerful
longevity drugs we currentlyknow, and science really does
say they are, how would yourapproach change if you shifted
your focus and your budget tomaximizing those things?
SPEAKER_02 (11:26):
That's the question.
If you treated your sleep andyour gym time with the same
commitment you'd give to anexpensive experimental pill,
what kind of longevity dividendwould you be paying yourself
right now?
SPEAKER_01 (11:39):
Think about that.
Are you truly maximizing yournon negotiable health
foundations before you eventhink about reaching for that
supplement stack?
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