November 28, 2025 • 13 mins
A no-regret longevity blueprint: VO2 max, lipid control, insulin health, APOB, sleep, and the habits that stack the odds for a longer life.
This episode breaks down the biggest levers that reliably extend lifespan—and why most longevity noise distracts from what truly moves the needle. We begin by reframing family history as a more accurate early risk guide than any single-gene test, including APOE, and highlight how APOE E4 is an actionable, preventable risk rather than a fixed destiny.
We dive into the four foundational pillars: exercise, lipid management, avoiding type 2 diabetes, and adequate sleep. You’ll learn how hazard ratios quantify the extraordinary impact of fitness and strength, why VO2 max dwarfs many common risk factors, and the practical training doses needed to build both aerobic capacity and muscle.
Next, we map the mechanisms of heart disease, including plaque biology, angiogenesis limitations, and why APOB testing and targeted pharmacology often outperform diet alone for lowering cardiovascular risk. We also discuss how poor sleep and cortisol directly strain the cardiovascular system.
The episode closes with a no-regret, measurable, sustainable system for stacking the odds in your favor—one habit at a time.
Listener Takeaways:
• Why family history beats single-gene testing for early risk
• APOE E4 as a modifiable, actionable risk
• The four primary levers of longevity
• VO2 max and strength hazard ratios
• APOB testing and practical cardiovascular strategy
Follow for daily longevity and wellness episodes.
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.
Never miss an episode—subscribe on your favorite podcast app!
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
SPEAKER_02 (00:00):
Okay, so let's unpack this.
We've dedicated this deep diveto a single uh a really critical
mission.
I want to give you a shortcut tolongevity.
We're gonna try and cut throughall the noise, all the
complexity, to identify what thesources are calling the true
no-regret moves.
These are the high-impact,actionable things that really
stand as our strongest defenses,specifically against the two
(00:23):
biggest threats, right?
Cognitive decline andcardiovascular disease.
SPEAKER_01 (00:27):
That's exactly right.
The sources we're drawing from,they focus ruthlessly on
prioritizing the evidence.
They're asking a simplequestion: where is the enormous
signal of benefit?
And the core message when youput it all together is
surprisingly clear.
We often, you know, we obsessover all these traditional risk
factors.
SPEAKER_02 (00:41):
But certain lifestyle metrics, and I mean
specifically things related tophysical fitness, they actually
dwarf most of the commonpredictors for all-cause
mortality.
Period.
And that's that's really thefoundation of this entire
discussion, isn't it?
We're moving past just anecdotesand into the uh the domain of
the hazard ratio.
But before we even get to thosenumbers, the ones that basically
(01:03):
prove exercise is king, I thinkwe need to clarify the starting
line for the brain.
So let's start withneurodegenerative disease.
SPEAKER_00 (01:11):
Good place to start.
And, you know, when you'retrying to gauge your risk for
something like Alzheimer's, thefirst instinct for a lot of
people is to go order a genetictest.
But the sources here are very,very firm on this.
For most of us, your familyhistory is often more telling.
It's more important than justrelying on a basic genetic
panel.
SPEAKER_02 (01:28):
Okay, that's a huge insight right out of the gate,
and it kind of runs counter tothis whole biohacking trend.
So why?
Why is that old-fashioned familystory potentially better than
modern genomics here?
SPEAKER_00 (01:38):
It really just comes down to scope.
The easiest gene to test for,the one you'll find on
commercial kits, is the APOEgene.
And it's important, don't get mewrong, but it's only one piece
of a much bigger puzzle.
I mean, there are at least adozen other genes, things like
APP, PSEN1, PSEN2, that arelinked to some forms of
dementia.
Usually they're reallyaggressive early onset types,
(02:00):
and those are just much harderto screen for.
SPEAKER_02 (02:03):
So family history gives you a pattern.
SPEAKER_00 (02:04):
It gives you a pattern, exactly.
It helps you understand the typeof dementia.
Is it Alzheimer's?
Vascular, frontotemporal.
And crucially, the age of onset.
That gives you context that asimple APOE test just can't
provide.
SPEAKER_02 (02:18):
Aaron Powell, and if you understand the type, that
completely changes theconversation around what you can
do about it.
SPEAKER_00 (02:22):
Aaron Powell Absolutely.
I mean the spectrum is broad.
You've got Alzheimer's, which isuh typically the most purely
cognitively destructive.
Then you have something likeParkinson's disease, which is
the most destructive tomovement.
And then there's Louis bodydementia, which is, well, it's
destructive to both.
So knowing which one runs in thefamily is key.
And as I said, knowing the ageof onset is maybe even more
important.
SPEAKER_02 (02:42):
Right.
So you're making a distinctionbetween those rare, really awful
early onset cases, the ones thatmight hit someone in their 40s
or 50s, and are sometimes linkedto those tougher to test genes
like PSEN1.
You're distinguishing that fromthe late-onset predisposition,
which is what we see in the vastmajority of cases, and that's
where APOE E4 comes in.
SPEAKER_00 (03:02):
Exactly.
Those early onset scenarios aredevastating, but for now,
there's less clarity on whatlifestyle changes can do.
But the most common gene forlate-onset Alzheimer's is that
APOE E4 variant.
And here is the trulymotivational part.
The sources categorize havingeven one copy of that gene, and
remember, about 25% of thepopulation has one.
(03:23):
They categorize it as beinghighly amenable to prevention.
SPEAKER_02 (03:26):
It just flips the entire script.
It means that genetic risk, atleast in this very common case,
isn't a death sense.
It's a call to action.
If you find out you have thatAPOE E4 gene, it should, what,
drastically increase howseriously you take all this
stuff even in your 30s?
SPEAKER_00 (03:40):
It should.
It absolutely should.
And knowing that genotypeactually makes your preventative
plan more specific, it informseverything, what kind of
anti-lipid medications you mightuse if you need them.
It helps determine the exactdosage for omega-3s, for EPA and
DHA.
And maybe most importantly, itlets you tailor how aggressive
you are with your exerciseprescription.
(04:02):
Especially for someone who'sshort on time, you know your
biggest vulnerability, so youpoint your biggest lever right
at it.
SPEAKER_02 (04:07):
Okay, that brings us right to the lever.
So what are they?
When we look at theinterventions with, as the
sources say, no ambiguity ofbenefit, what's the list?
SPEAKER_00 (04:17):
The list is compact.
The huge signal interventions.
There are four.
And if you rank them in roughorder of impact, the hierarchy
is crystal clear.
Number one, exercise.
Number two, lipid management.
Number three, not having typetwo diabetes.
And number four, adequate sleep.
SPEAKER_02 (04:33):
Exercise at the top, towering over everything else.
To really get our heads aroundjust how massive that benefit
is, we have to introduce thismetric.
SPEAKER_00 (04:40):
Hmm.
SPEAKER_02 (04:40):
The hazard ratio.
SPEAKER_00 (04:42):
Yes, the hazard ratio, or HR.
It's the critical tool here.
And let's just compare the riskof, well, of dying or having a
bad outcome in one group versusanother.
So an HR of 1.0 is yourbaseline.
No difference in risk.
An HR of 1.5 means your group is50% riskier than the baseline
group.
And on the flip side, an HR ofDort 7.5 means you are 25% less
(05:02):
risky.
SPEAKER_02 (05:03):
Okay.
Let's give that some context.
Use some common risk factors forall-cause mortality, the things
we hear about all the time.
SPEAKER_00 (05:08):
Sure.
So if you look at chronicsmoking, the hazard ratio is
generally around a 1.4.
So a 40% increased chance ofdying in a given year compared
to a nonsmoker.
If we look at, say, uncontrolledhypertension, high blood
pressure, the HR is about 1.2.
So 20% riskier.
And just for uh you knowdramatic comparison, end-stage
kidney disease, patients ondialysis, they're dealing with
(05:30):
an HR of 2.75.
That's a huge 175% increasedmortality rate.
SPEAKER_02 (05:34):
Those are terrible numbers.
unknown (05:35):
Yeah.
SPEAKER_02 (05:36):
And they're why we focus so much on those
conditions.
But now, let's bring incardiorespiratory fitness.
This is where the data justbecomes well, it's almost
unbelievable.
Trevor Burrus, Jr.
SPEAKER_00 (05:44):
It dwarfs them.
It absolutely dwarfs thosecommon risks.
If you look at VO2 Max, that'sthe gold standard for your
cardiorespiratory fitness.
The comparison is just stark.
If you compare someone in thebottom 25% of fitness for their
age to someone in the top 2%,the hazard ratio is five.
SPEAKER_02 (05:59):
Aaron Powell An HR of five.
I mean, let's just pause onthat.
That's a 400% difference inmortality risk.
Just that single lever, yourfitness level, carries a signal
five times greater than notbeing a smoker.
It's it's just incredible.
SPEAKER_00 (06:12):
Aaron Powell It really is.
It basically underscores thisidea that your cardiovascular
fitness is maybe the singlegreatest predictor of how long
you're gonna live.
SPEAKER_02 (06:19):
Aaron Powell I have to ask this though, for anyone
listening, when they hear top2%, that sounds like an elite
athlete.
What does that actually looklike?
Are we talking about someonerunning marathons every weekend,
or is this something anordinary, motivated person can
actually achieve?
SPEAKER_00 (06:33):
That is the critical question.
And no, we are not necessarilytalking about elite Olympic
level performance, but we aretalking about consistency and
intention.
The sources are pretty clearthat getting to that high-end
fitness level requires dedicatedendurance training.
It means multiple sessions aweek where you are pushing your
heart rate.
It's not just a casual walk, youhave to take it seriously.
(06:54):
Maybe that means high-intensityinterval training or just a very
high volume of moderate cardio.
It's hard work, yes, but it isabsolutely attainable for
someone who commits, say, fourto five hours a week to
intentional training.
SPEAKER_02 (07:08):
Aaron Powell So the reward is massive and it's
within reach.
And it's not just about cardio,is it you mentioned strength?
SPEAKER_00 (07:13):
Aaron Powell Correct.
And we have to avoid this cardioversus strength debate.
It's always and the sources showthat if you compare somebody in
the bottom quartile of musclestrength to the top quartile,
the HR is about three.
So that confirms it.
Metrics for muscle mass andstrength also have a massive
protective effect.
You need both.
SPEAKER_02 (07:30):
Okay.
So we've stacked the odds forthe brain.
Exercise, lipids, diabetescontrol, sleep.
Now let's pivot to the heart.
It's still the biggest killerglobally.
Why does this amazing muscle,the heart, seem so vulnerable?
SPEAKER_00 (07:44):
You know, I actually challenge the idea that the
heart is fragile.
It's a beautifully robustmachine.
Its vulnerability is itsinfrastructure, the blood
supply.
It's very narrow.
The heart's biggest drawbackcompared to, say, your quad
muscle is its limited capacityfor something called
angiogenesis.
That's the ability to regrowblood vessels around a blockage.
SPEAKER_02 (08:05):
So if a vessel in my leg gets clogged up, my body's
better at just growing newpathways around it.
But in the heart, if theplumbing gets clogged, the
tissue just dies quickly.
SPEAKER_00 (08:14):
Exactly.
The stakes are immediately lifeor death.
And this is where evolutioncomes in.
Evolution just it didn't careabout chronic atherosclerosis
because the things that drive itdidn't really affect our ability
to reproduce.
People had kids long beforethese diseases showed up.
SPEAKER_02 (08:27):
And the sources are very clear on the three main
drivers of this modern problem: smoking, high blood pressure, (08:29):
undefined
and high APOB.
Let's dig into that third one.
SPEAKER_00 (08:36):
APOB is fascinating.
It really gives you themechanism.
It's the uh the primary proteinwrapper that carries
cholesterol, specifically LDLand VLDL particles, into your
tissues.
Now, in a world where food wasscarce, having a high capacity
to carry and deposit fat, thatmight have been a huge
advantage.
It could have helped you survivea famine.
(08:56):
But today, in a world of caloricabundance, it's highly
problematic.
SPEAKER_02 (09:01):
And the way it attacks is counterintuitive.
It's not just the fat itself,it's how the body reacts to it.
SPEAKER_00 (09:06):
Aaron Powell That is the key insight.
These tiny APOB particles, theycarry cholesterol and they can
get into the walls of yourarteries.
When they do, the immune systemsees them.
It treats this buildup like aforeign invader.
And so it mounts this biginflammatory response.
But that response, while it'strying to help, is what leads to
the creation of plaques.
It's the body's attempt to walloff this perceived threat.
SPEAKER_02 (09:26):
Aaron Powell So the immune system is just doing its
job, but the byproduct of thatjob is the very plaque that can
rupture and cause a heartattack.
SPEAKER_00 (09:34):
Precisely.
It's a catastrophic defensiveerror.
The ultimate goal then is justto eliminate the trigger.
If you can eradicate those threedrivers smoking, high blood
pressure and high APOB, itbecomes exceedingly difficult to
develop atherosclerosis in thefirst place.
SPEAKER_02 (09:49):
Aaron Powell Okay, so if eradication is the goal,
what are the actionable targetsfor someone listening?
SPEAKER_00 (09:53):
Aaron Powell It comes down to two key numbers.
First, maintain your bloodpressure at or ideally below 120
over 80.
And second, maintain your APOBat the physiologic level that
you see in healthy children.
That is the true baseline ofhealth.
SPEAKER_02 (10:07):
Aaron Powell That sounds very aggressive.
How do you even start monitoringAPOB?
Is that some kind of specialtytest?
SPEAKER_00 (10:13):
Aaron Powell Not at all.
It's a standard blood test.
It's easily accessible and oftencosts around, I think,$12.
For anyone who's reallymotivated, tracking it three or
four times a year is essentialto make sure you're on target.
And if that number is high, thequestion immediately becomes not
if you should treat it, but how?
How aggressively?
With lifestyle or withpharmacology?
SPEAKER_02 (10:32):
Aaron Powell And this is where the sources get
into a really interestingphilosophical argument.
We just established thatexercise is the biggest lever
with that HR of five.
Lipid management is number twofor the brain.
So why do the sources suggestthat getting to those very, very
low levels of APOB oftenrequires pharmacology for most
people?
Why not just push an aggressivediet?
SPEAKER_00 (10:53):
That's an excellent point, and it's one that
deserves some scrutiny.
Of course, an aggressive diet,like an extremely low-fat diet,
can certainly lower APOB.
But the sources highlight thetrade-off.
We're always looking for thingsthat solve one problem without
creating new ones.
And for many people, getting tothose kid level APOB numbers
requires such draconiannutritional steps that it risks
(11:16):
creating other issues, hormonedisruption, problems with
maintaining muscle, or it's justplain unsustainable.
SPEAKER_02 (11:21):
So we're back to that no-regret move idea.
Using a targeted medication likean anti-lipid therapy to solve
the specific APOB problemwithout forcing you onto an
unsustainable diet that mightcompromise your muscle mass, the
very thing that gives you thatmassive protective benefit.
That's seen as the bettertrade-off.
SPEAKER_00 (11:39):
Exactly.
The source material callsanti-lipid therapy Medicine
2.0's second biggest win, rightafter antibiotics.
It's a targeted solution.
It lets you fix the plumbingissue without jeopardizing the
huge benefits you get from beingstrong and having great cardio.
SPEAKER_02 (11:54):
We've covered the chemical and fitness livers, but
we can't forget the other thingsthat feed into this system.
Poor sleep and high stress arethey're everywhere in these
sources as powerful disruptors.
SPEAKER_00 (12:05):
Absolutely.
Poor sleep has just devastatingimpacts on the heart.
It often works through increasedsympathetic overtone, which just
means your fight or flightsystem is constantly running a
little too high, and throughhypercortisanemia.
SPEAKER_02 (12:18):
High levels of cortisol, the stress hormone.
SPEAKER_00 (12:20):
Yes.
And the data linking chronicallyhigh cortisol to direct damage
in the coronary arteries is veryclear.
You know, cortisol isn't just afeeling, it's a potent
biological agent and it damagesyour vascular health.
So managing stress, prioritizingsleep, these are just as
critical as hitting your VO2 maxtargets.
SPEAKER_02 (12:38):
So when you put it all together, what does this
mean for the listener who'strying to synthesize all this?
SPEAKER_00 (12:43):
I think the core message is holistic, but it's
also empowering.
This is not a zero-sum game.
The goal is to stack the odds inyour favor.
Aggressively, be strong, have ahigh VO2 max, prioritize your
sleep, don't smoke, manage yourblood pressure, and use targeted
interventions, whether that'snutrition or pharmacology, to
keep your APOB at a level that'sactually conducive to survival
(13:05):
in the modern world.
And of course, we always have toacknowledge that there is a
stochastic element to life whererandom bad luck happens.
But the focus has to remain oncontrolling what you can
control, and that is atremendous amount of that focus
on control is powerful.
SPEAKER_02 (13:18):
And it brings us right back to where we started.
We saw that APOB, this particlethat drives azerosclerosis
today, was probably beneficialin the scarce nutrient world.
It was an evolutionary trade.
So my final thought for you isthis given the immense power of
a high VO2 max, that hazardratio of five to protect us, we
other physiological traits thatwere once highly beneficial for
(13:41):
survival in our deep past mightnow be inadvertently
contributing to chronic diseasein our modern environment.
What other evolutionary trades,besides our cholesterol
transport system, might we bepaying for today?
Something to think about.
Okay, so let's unpack this.
We've dedicated this deep diveto a single uh a really critical
mission.
I want to give you a shortcut tolongevity.
We're gonna try and cut throughall the noise, all the
complexity, to identify what thesources are calling the true
no-regret moves.
These are the high-impact,actionable things that really
stand as our strongest defenses,specifically against the two
(00:23):
biggest threats, right?
Cognitive decline andcardiovascular disease.
SPEAKER_01 (00:27):
That's exactly right.
The sources we're drawing from,they focus ruthlessly on
prioritizing the evidence.
They're asking a simplequestion: where is the enormous
signal of benefit?
And the core message when youput it all together is
surprisingly clear.
We often, you know, we obsessover all these traditional risk
factors.
SPEAKER_02 (00:41):
But certain lifestyle metrics, and I mean
specifically things related tophysical fitness, they actually
dwarf most of the commonpredictors for all-cause
mortality.
Period.
And that's that's really thefoundation of this entire
discussion, isn't it?
We're moving past just anecdotesand into the uh the domain of
the hazard ratio.
But before we even get to thosenumbers, the ones that basically
(01:03):
prove exercise is king, I thinkwe need to clarify the starting
line for the brain.
So let's start withneurodegenerative disease.
SPEAKER_00 (01:11):
Good place to start.
And, you know, when you'retrying to gauge your risk for
something like Alzheimer's, thefirst instinct for a lot of
people is to go order a genetictest.
But the sources here are very,very firm on this.
For most of us, your familyhistory is often more telling.
It's more important than justrelying on a basic genetic
panel.
SPEAKER_02 (01:28):
Okay, that's a huge insight right out of the gate,
and it kind of runs counter tothis whole biohacking trend.
So why?
Why is that old-fashioned familystory potentially better than
modern genomics here?
SPEAKER_00 (01:38):
It really just comes down to scope.
The easiest gene to test for,the one you'll find on
commercial kits, is the APOEgene.
And it's important, don't get mewrong, but it's only one piece
of a much bigger puzzle.
I mean, there are at least adozen other genes, things like
APP, PSEN1, PSEN2, that arelinked to some forms of
dementia.
Usually they're reallyaggressive early onset types,
(02:00):
and those are just much harderto screen for.
SPEAKER_02 (02:03):
So family history gives you a pattern.
SPEAKER_00 (02:04):
It gives you a pattern, exactly.
It helps you understand the typeof dementia.
Is it Alzheimer's?
Vascular, frontotemporal.
And crucially, the age of onset.
That gives you context that asimple APOE test just can't
provide.
SPEAKER_02 (02:18):
Aaron Powell, and if you understand the type, that
completely changes theconversation around what you can
do about it.
SPEAKER_00 (02:22):
Aaron Powell Absolutely.
I mean the spectrum is broad.
You've got Alzheimer's, which isuh typically the most purely
cognitively destructive.
Then you have something likeParkinson's disease, which is
the most destructive tomovement.
And then there's Louis bodydementia, which is, well, it's
destructive to both.
So knowing which one runs in thefamily is key.
And as I said, knowing the ageof onset is maybe even more
important.
SPEAKER_02 (02:42):
Right.
So you're making a distinctionbetween those rare, really awful
early onset cases, the ones thatmight hit someone in their 40s
or 50s, and are sometimes linkedto those tougher to test genes
like PSEN1.
You're distinguishing that fromthe late-onset predisposition,
which is what we see in the vastmajority of cases, and that's
where APOE E4 comes in.
SPEAKER_00 (03:02):
Exactly.
Those early onset scenarios aredevastating, but for now,
there's less clarity on whatlifestyle changes can do.
But the most common gene forlate-onset Alzheimer's is that
APOE E4 variant.
And here is the trulymotivational part.
The sources categorize havingeven one copy of that gene, and
remember, about 25% of thepopulation has one.
(03:23):
They categorize it as beinghighly amenable to prevention.
SPEAKER_02 (03:26):
It just flips the entire script.
It means that genetic risk, atleast in this very common case,
isn't a death sense.
It's a call to action.
If you find out you have thatAPOE E4 gene, it should, what,
drastically increase howseriously you take all this
stuff even in your 30s?
SPEAKER_00 (03:40):
It should.
It absolutely should.
And knowing that genotypeactually makes your preventative
plan more specific, it informseverything, what kind of
anti-lipid medications you mightuse if you need them.
It helps determine the exactdosage for omega-3s, for EPA and
DHA.
And maybe most importantly, itlets you tailor how aggressive
you are with your exerciseprescription.
(04:02):
Especially for someone who'sshort on time, you know your
biggest vulnerability, so youpoint your biggest lever right
at it.
SPEAKER_02 (04:07):
Okay, that brings us right to the lever.
So what are they?
When we look at theinterventions with, as the
sources say, no ambiguity ofbenefit, what's the list?
SPEAKER_00 (04:17):
The list is compact.
The huge signal interventions.
There are four.
And if you rank them in roughorder of impact, the hierarchy
is crystal clear.
Number one, exercise.
Number two, lipid management.
Number three, not having typetwo diabetes.
And number four, adequate sleep.
SPEAKER_02 (04:33):
Exercise at the top, towering over everything else.
To really get our heads aroundjust how massive that benefit
is, we have to introduce thismetric.
SPEAKER_00 (04:40):
Hmm.
SPEAKER_02 (04:40):
The hazard ratio.
SPEAKER_00 (04:42):
Yes, the hazard ratio, or HR.
It's the critical tool here.
And let's just compare the riskof, well, of dying or having a
bad outcome in one group versusanother.
So an HR of 1.0 is yourbaseline.
No difference in risk.
An HR of 1.5 means your group is50% riskier than the baseline
group.
And on the flip side, an HR ofDort 7.5 means you are 25% less
(05:02):
risky.
SPEAKER_02 (05:03):
Okay.
Let's give that some context.
Use some common risk factors forall-cause mortality, the things
we hear about all the time.
SPEAKER_00 (05:08):
Sure.
So if you look at chronicsmoking, the hazard ratio is
generally around a 1.4.
So a 40% increased chance ofdying in a given year compared
to a nonsmoker.
If we look at, say, uncontrolledhypertension, high blood
pressure, the HR is about 1.2.
So 20% riskier.
And just for uh you knowdramatic comparison, end-stage
kidney disease, patients ondialysis, they're dealing with
(05:30):
an HR of 2.75.
That's a huge 175% increasedmortality rate.
SPEAKER_02 (05:34):
Those are terrible numbers.
unknown (05:35):
Yeah.
SPEAKER_02 (05:36):
And they're why we focus so much on those
conditions.
But now, let's bring incardiorespiratory fitness.
This is where the data justbecomes well, it's almost
unbelievable.
Trevor Burrus, Jr.
SPEAKER_00 (05:44):
It dwarfs them.
It absolutely dwarfs thosecommon risks.
If you look at VO2 Max, that'sthe gold standard for your
cardiorespiratory fitness.
The comparison is just stark.
If you compare someone in thebottom 25% of fitness for their
age to someone in the top 2%,the hazard ratio is five.
SPEAKER_02 (05:59):
Aaron Powell An HR of five.
I mean, let's just pause onthat.
That's a 400% difference inmortality risk.
Just that single lever, yourfitness level, carries a signal
five times greater than notbeing a smoker.
It's it's just incredible.
SPEAKER_00 (06:12):
Aaron Powell It really is.
It basically underscores thisidea that your cardiovascular
fitness is maybe the singlegreatest predictor of how long
you're gonna live.
SPEAKER_02 (06:19):
Aaron Powell I have to ask this though, for anyone
listening, when they hear top2%, that sounds like an elite
athlete.
What does that actually looklike?
Are we talking about someonerunning marathons every weekend,
or is this something anordinary, motivated person can
actually achieve?
SPEAKER_00 (06:33):
That is the critical question.
And no, we are not necessarilytalking about elite Olympic
level performance, but we aretalking about consistency and
intention.
The sources are pretty clearthat getting to that high-end
fitness level requires dedicatedendurance training.
It means multiple sessions aweek where you are pushing your
heart rate.
It's not just a casual walk, youhave to take it seriously.
(06:54):
Maybe that means high-intensityinterval training or just a very
high volume of moderate cardio.
It's hard work, yes, but it isabsolutely attainable for
someone who commits, say, fourto five hours a week to
intentional training.
SPEAKER_02 (07:08):
Aaron Powell So the reward is massive and it's
within reach.
And it's not just about cardio,is it you mentioned strength?
SPEAKER_00 (07:13):
Aaron Powell Correct.
And we have to avoid this cardioversus strength debate.
It's always and the sources showthat if you compare somebody in
the bottom quartile of musclestrength to the top quartile,
the HR is about three.
So that confirms it.
Metrics for muscle mass andstrength also have a massive
protective effect.
You need both.
SPEAKER_02 (07:30):
Okay.
So we've stacked the odds forthe brain.
Exercise, lipids, diabetescontrol, sleep.
Now let's pivot to the heart.
It's still the biggest killerglobally.
Why does this amazing muscle,the heart, seem so vulnerable?
SPEAKER_00 (07:44):
You know, I actually challenge the idea that the
heart is fragile.
It's a beautifully robustmachine.
Its vulnerability is itsinfrastructure, the blood
supply.
It's very narrow.
The heart's biggest drawbackcompared to, say, your quad
muscle is its limited capacityfor something called
angiogenesis.
That's the ability to regrowblood vessels around a blockage.
SPEAKER_02 (08:05):
So if a vessel in my leg gets clogged up, my body's
better at just growing newpathways around it.
But in the heart, if theplumbing gets clogged, the
tissue just dies quickly.
SPEAKER_00 (08:14):
Exactly.
The stakes are immediately lifeor death.
And this is where evolutioncomes in.
Evolution just it didn't careabout chronic atherosclerosis
because the things that drive itdidn't really affect our ability
to reproduce.
People had kids long beforethese diseases showed up.
SPEAKER_02 (08:27):
And the sources are very clear on the three main
drivers of this modern problem: smoking, high blood pressure, (08:29):
undefined
and high APOB.
Let's dig into that third one.
SPEAKER_00 (08:36):
APOB is fascinating.
It really gives you themechanism.
It's the uh the primary proteinwrapper that carries
cholesterol, specifically LDLand VLDL particles, into your
tissues.
Now, in a world where food wasscarce, having a high capacity
to carry and deposit fat, thatmight have been a huge
advantage.
It could have helped you survivea famine.
(08:56):
But today, in a world of caloricabundance, it's highly
problematic.
SPEAKER_02 (09:01):
And the way it attacks is counterintuitive.
It's not just the fat itself,it's how the body reacts to it.
SPEAKER_00 (09:06):
Aaron Powell That is the key insight.
These tiny APOB particles, theycarry cholesterol and they can
get into the walls of yourarteries.
When they do, the immune systemsees them.
It treats this buildup like aforeign invader.
And so it mounts this biginflammatory response.
But that response, while it'strying to help, is what leads to
the creation of plaques.
It's the body's attempt to walloff this perceived threat.
SPEAKER_02 (09:26):
Aaron Powell So the immune system is just doing its
job, but the byproduct of thatjob is the very plaque that can
rupture and cause a heartattack.
SPEAKER_00 (09:34):
Precisely.
It's a catastrophic defensiveerror.
The ultimate goal then is justto eliminate the trigger.
If you can eradicate those threedrivers smoking, high blood
pressure and high APOB, itbecomes exceedingly difficult to
develop atherosclerosis in thefirst place.
SPEAKER_02 (09:49):
Aaron Powell Okay, so if eradication is the goal,
what are the actionable targetsfor someone listening?
SPEAKER_00 (09:53):
Aaron Powell It comes down to two key numbers.
First, maintain your bloodpressure at or ideally below 120
over 80.
And second, maintain your APOBat the physiologic level that
you see in healthy children.
That is the true baseline ofhealth.
SPEAKER_02 (10:07):
Aaron Powell That sounds very aggressive.
How do you even start monitoringAPOB?
Is that some kind of specialtytest?
SPEAKER_00 (10:13):
Aaron Powell Not at all.
It's a standard blood test.
It's easily accessible and oftencosts around, I think,$12.
For anyone who's reallymotivated, tracking it three or
four times a year is essentialto make sure you're on target.
And if that number is high, thequestion immediately becomes not
if you should treat it, but how?
How aggressively?
With lifestyle or withpharmacology?
SPEAKER_02 (10:32):
Aaron Powell And this is where the sources get
into a really interestingphilosophical argument.
We just established thatexercise is the biggest lever
with that HR of five.
Lipid management is number twofor the brain.
So why do the sources suggestthat getting to those very, very
low levels of APOB oftenrequires pharmacology for most
people?
Why not just push an aggressivediet?
SPEAKER_00 (10:53):
That's an excellent point, and it's one that
deserves some scrutiny.
Of course, an aggressive diet,like an extremely low-fat diet,
can certainly lower APOB.
But the sources highlight thetrade-off.
We're always looking for thingsthat solve one problem without
creating new ones.
And for many people, getting tothose kid level APOB numbers
requires such draconiannutritional steps that it risks
(11:16):
creating other issues, hormonedisruption, problems with
maintaining muscle, or it's justplain unsustainable.
SPEAKER_02 (11:21):
So we're back to that no-regret move idea.
Using a targeted medication likean anti-lipid therapy to solve
the specific APOB problemwithout forcing you onto an
unsustainable diet that mightcompromise your muscle mass, the
very thing that gives you thatmassive protective benefit.
That's seen as the bettertrade-off.
SPEAKER_00 (11:39):
Exactly.
The source material callsanti-lipid therapy Medicine
2.0's second biggest win, rightafter antibiotics.
It's a targeted solution.
It lets you fix the plumbingissue without jeopardizing the
huge benefits you get from beingstrong and having great cardio.
SPEAKER_02 (11:54):
We've covered the chemical and fitness livers, but
we can't forget the other thingsthat feed into this system.
Poor sleep and high stress arethey're everywhere in these
sources as powerful disruptors.
SPEAKER_00 (12:05):
Absolutely.
Poor sleep has just devastatingimpacts on the heart.
It often works through increasedsympathetic overtone, which just
means your fight or flightsystem is constantly running a
little too high, and throughhypercortisanemia.
SPEAKER_02 (12:18):
High levels of cortisol, the stress hormone.
SPEAKER_00 (12:20):
Yes.
And the data linking chronicallyhigh cortisol to direct damage
in the coronary arteries is veryclear.
You know, cortisol isn't just afeeling, it's a potent
biological agent and it damagesyour vascular health.
So managing stress, prioritizingsleep, these are just as
critical as hitting your VO2 maxtargets.
SPEAKER_02 (12:38):
So when you put it all together, what does this
mean for the listener who'strying to synthesize all this?
SPEAKER_00 (12:43):
I think the core message is holistic, but it's
also empowering.
This is not a zero-sum game.
The goal is to stack the odds inyour favor.
Aggressively, be strong, have ahigh VO2 max, prioritize your
sleep, don't smoke, manage yourblood pressure, and use targeted
interventions, whether that'snutrition or pharmacology, to
keep your APOB at a level that'sactually conducive to survival
(13:05):
in the modern world.
And of course, we always have toacknowledge that there is a
stochastic element to life whererandom bad luck happens.
But the focus has to remain oncontrolling what you can
control, and that is atremendous amount of that focus
on control is powerful.
SPEAKER_02 (13:18):
And it brings us right back to where we started.
We saw that APOB, this particlethat drives azerosclerosis
today, was probably beneficialin the scarce nutrient world.
It was an evolutionary trade.
So my final thought for you isthis given the immense power of
a high VO2 max, that hazardratio of five to protect us, we
other physiological traits thatwere once highly beneficial for
(13:41):
survival in our deep past mightnow be inadvertently
contributing to chronic diseasein our modern environment.
What other evolutionary trades,besides our cholesterol
transport system, might we bepaying for today?
Something to think about.
Popular Podcasts
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
Las Culturistas with Matt Rogers and Bowen Yang
Ding dong! Join your culture consultants, Matt Rogers and Bowen Yang, on an unforgettable journey into the beating heart of CULTURE. Alongside sizzling special guests, they GET INTO the hottest pop-culture moments of the day and the formative cultural experiences that turned them into Culturistas. Produced by the Big Money Players Network and iHeartRadio.
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.