May 16, 2026 • 23 mins
We stop obsessing over wrinkles and start looking at the real “cellular battery” that powers aging: NAD+. We weigh the hype against NIH workshop science, clinical trial signals, and the blunt reminder that exercise can raise NAD+ to youthful levels without a biohacker budget.
• NAD+ as a coenzyme that converts food into ATP
• NAD+ role in DNA repair enzymes and cellular maintenance
• sirtuins debate and why top researchers disagree
• Sinclair’s NMN mouse data and frailty clock claims
• Brenner’s evolutionary argument for stress response biology
• NAD World signaling between adipose tissue and hypothalamus
• microbiome trade that helps the host synthesize NAD+
• why oral NAD+ fails and precursors like NR and NMN dominate
• first-pass metabolism limits supplements and drives IV therapy demand
• NR vs NMN head-to-head data on blood NAD+ increases
• brain NAD+ challenges and why consistent dosing matters
• clinical trial mechanisms for blood pressure, insulin sensitivity, and mitophagy
• the exercise finding that reframes the whole longevity narrative
• aging as a communication breakdown across organs
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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SPEAKER_01 (00:00):
So when most of us buy a new smartphone, we
completely obsess over like allthe visible things, right?
SPEAKER_00 (00:05):
Yeah, the sleek glass, the camera lenses.
SPEAKER_01 (00:07):
Exactly.
How thin it is.
But we completely ignore thebattery.
I mean, at least until it's like2.0 p.m., your screen goes dark,
and suddenly literally nothingelse about the phone matters.
SPEAKER_00 (00:17):
Right.
Because the hardware is entirelyuseless without the charge.
SPEAKER_01 (00:20):
Right.
And the thing is, we treat ourbodies the exact same way.
We obsess over this surfacelevel aging.
So wrinkles, gray hair, losingmuscle tone while just
completely ignoring the cellularbattery that actually, you know,
powers our existence.
SPEAKER_00 (00:34):
Aaron Powell Yeah, we're so entirely focused on the
cosmetic symptoms.
Meanwhile, the true mechanism ofaging is happening quietly on
this microscopic energeticlevel.
SPEAKER_01 (00:44):
Aaron Powell Which brings us to what we're doing
today.
We are taking a deep dive intothe raw science of that cellular
battery, a molecule called NADplus ornato or uh nicotinamide
adenine to nucleotide.
SPEAKER_00 (00:56):
Always a mouthful.
SPEAKER_01 (00:57):
Yeah, truly.
But we've got a massive stack ofsources today to help us just
cut through the multi-billiondollar hype of the whole
anti-aging industry.
SPEAKER_00 (01:05):
And the sources are fantastic.
We're looking at the highlycomprehensive 2021 National
Institutes of Health workshoptranscripts.
SPEAKER_01 (01:13):
Right, featuring literally the pioneers of aging
research.
Plus, we've got a historicalreview from the journal Cell
Metabolism, some really freshclinical trial data, and even
the operational notes from anactual IV therapy clinic, Santa
Fe Mobile MD.
SPEAKER_00 (01:28):
So we're really covering it from the theoretical
lab work all the way to theclinical application.
SPEAKER_01 (01:33):
Exactly.
Our mission for you listening isto basically bypass all those
flashy supplement ads you seeonline and figure out the actual
biology.
Because looking at these NIHworkshop transcripts, man, these
researchers are practically ateach other's throats.
SPEAKER_00 (01:47):
It is a phenomenal clash of perspectives, honestly.
But you know, to reallyunderstand why they're arguing,
we first have to look at whatNAD plus physically does in your
body.
SPEAKER_01 (01:55):
Right.
Let's lay the groundwork.
SPEAKER_00 (01:57):
At its core, it's what we call a coenzyme.
So it's this fundamental helpermolecule that is literally found
in every single living cell.
It acts as the essentialdelivery truck for cellular
energy.
SPEAKER_01 (02:09):
So when you eat a meal, right.
SPEAKER_00 (02:10):
When you eat, NAD Plus is absolutely required to
convert the nutrients from yourfood into ATP.
And ATP is the actual chemicalcurrency your cells spend to
keep your heart beating, to keepyou breathing.
SPEAKER_01 (02:22):
So without NAD Plus, your biology simply halts.
It's like the ultimatebiological spark plug.
SPEAKER_00 (02:28):
Exactly.
But it's the secondary role ofNAD Plus that actually triggered
this whole massive longevityindustry.
It fuels the enzymes that repairdamaged DNA.
SPEAKER_01 (02:37):
And looking at that cell metabolism historical
review, the trajectory of how wediscovered this is just wild.
SPEAKER_00 (02:44):
Oh, it really is.
It spans over a century.
SPEAKER_01 (02:46):
Yeah.
It starts back in 1906 withthese two researchers, Harden
and Young, and they wereliterally just studying yeast
fermentation for brewing.
SPEAKER_00 (02:53):
Right, a very different application.
SPEAKER_01 (02:54):
And then cut to 1949, scientist Conrad Elvium
links the NAD plus precursor,which is vitamin B3, to curing
Pellagra, which was thishorrific fatal disease.
SPEAKER_00 (03:06):
Right, characterized by dermatitis and severe
dementia.
SPEAKER_01 (03:09):
Yeah, and they initially studied it as black
tongue in dogs, which is crazyto think about.
SPEAKER_00 (03:13):
It really is.
And, you know, the jump frombrewing yeast and canine
pellagra to human longevity,that took decades.
SPEAKER_01 (03:20):
Decades.
So when did the paradigmactually shift?
SPEAKER_00 (03:23):
Aaron Ross Powell That would be around the year
2000.
Leonard Garante and ShinichiroImai made this truly monumental
connection.
They discovered that NAD plus isthe mandatory fuel for a class
of proteins called sirtuins.
SPEAKER_01 (03:37):
Sirtuins, you hear that word a lot in biohacking
circles.
SPEAKER_00 (03:40):
Oh, constantly.
Because sirtuins essentially actas your cellular guardians.
They repair DNA, they manageinflammation, they regulate your
metabolic health.
But and this is the key, theyare completely NAD dependent.
SPEAKER_01 (03:51):
Aaron Powell So they need the battery to run.
SPEAKER_00 (03:53):
Aaron Powell Exactly.
And the problem is as we age,our NAD plus supply just
plummets, which means theseguardians are essentially
starved of the fuel they need toactually protect us.
SPEAKER_01 (04:02):
Aaron Powell Okay.
Which brings us to thisheavyweight bout in the NIH
workshop notes.
Because there's a massive fightover how these sertuans actually
fit into the whole agingprocess.
SPEAKER_00 (04:10):
Aaron Powell Yeah, it gets quite heated.
SPEAKER_01 (04:12):
Aaron Powell David Sinclair from Harvard University
presented some incrediblyaggressive data here.
I mean he's arguing thatsertuans are dedicated longevity
genes.
SPEAKER_00 (04:20):
Aaron Powell Right, that they are explicitly
designed to keep us young.
SPEAKER_01 (04:23):
Exactly.
And he showed that supplementingmice with an NAD plus precursor,
NMN, dramatically improves theirmetabolic health.
He even uses these machinelearning algorithms.
They're called the FRIT andAFARAID clocks.
SPEAKER_00 (04:37):
Clever acronyms in this field.
SPEAKER_01 (04:38):
Very clever.
It stands for Frailty InferredGeriatric Health Timeline.
And he yells them to show thatchronic NMN treatment actually
lowers frailty scores in miceand predicts a longer lifespan.
He's basically framing NED plusas the key to just turning these
longevity genes back on.
SPEAKER_00 (04:56):
So Sinclair's whole narrative is that we have this
ancient survival circuit insideus that we can biohack.
SPEAKER_01 (05:01):
Right.
But then Charles Brenner fromThe City of Hope steps up and he
essentially just throws agrenade at that entire premise.
SPEAKER_00 (05:07):
He really does.
I mean, his abstract bluntlystates, and I quote, 99% of what
you've been told about Sirtuansand longevity is wrong.
SPEAKER_01 (05:15):
Yeah, he calls the global focus on Sirtuans as
longevity regulatorsintellectually bankrupt.
Which, I mean, that is notstandard academic politeness.
SPEAKER_00 (05:25):
Not at all.
Brenner is arguing from a verystrict evolutionary biology
perspective here.
His main point is that animalswere never evolutionarily
selected to have genes dedicatedto making them live longer.
SPEAKER_01 (05:37):
Because evolution only cares about reproduction.
SPEAKER_00 (05:39):
Exactly.
Evolution only selects fortraits that help you survive
long enough to reproduce andraise your young.
Once you've done that, strictlyspeaking, you are biologically
dispensable.
SPEAKER_01 (05:49):
Wow, harsh reality.
SPEAKER_00 (05:51):
It is.
So from that view, allocatingprecious cellular energy to
keeping a post-reproductiveorganism young, that would
actually be a severeevolutionary disadvantage.
SPEAKER_01 (05:59):
So what does Brenner think NAD Plus is doing then?
SPEAKER_00 (06:02):
He argues that NAD Plus and Sirtuans aren't these
magical anti-aging switches.
They're simply part of a stressresponse system.
It's just the fuel our cells useto repair the daily, unavoidable
damage caused by metabolizingfood and fighting off pathogens.
SPEAKER_01 (06:17):
Okay, I want to neutrally frame this debate for
anyone trying to make sense ofthe science, because we're not
taking sides here.
And both of these guys havebrilliant researchers behind
them.
SPEAKER_00 (06:27):
Absolutely.
SPEAKER_01 (06:27):
Let's think of NAD Plus as the oil in your car's
engine.
Sinclair is arguing that thisspecific oil interacts with this
hidden high-tech computer chipin the car, the Sirtuans, that
actually reverses the age of theengine components.
SPEAKER_00 (06:41):
Right.
SPEAKER_01 (06:41):
But Brenner is arguing that no, there is no
magic computer chip.
The oil simply stops the pistonsfrom grinding together and
seizing up when you push theengine too hard.
SPEAKER_00 (06:51):
That's a great way to put it.
SPEAKER_01 (06:52):
But regardless of the underlying mechanism,
whether it's unlocking truelongevity or just mitigating
stress, both camps absolutelyagree on one thing.
If your car runs out of oil, theengine dies.
You need the NAD plus NITUS.
SPEAKER_00 (07:04):
Yes.
The absolute consensus at theworkshop, despite all those
fiery disagreements onevolutionary intent, is that
replenishing the NAD plusmetabolome is highly beneficial
for maintaining tissue health.
SPEAKER_01 (07:16):
But the way our tissues actually manage that
supply, that is where thebiology gets genuinely strange.
Because you would assume amolecule this critical would
just be hoarded by everyindividual cell, right?
Every cell for itself.
SPEAKER_00 (07:28):
You would think so.
But Shinichiro Imai's researchoutlines something he calls the
NAD World 3.0, and it revealsthis highly complex,
decentralized communicationnetwork across your entire body.
SPEAKER_01 (07:41):
And the boss of this whole network is your adipose
tissue, which is essentiallyyour body fat.
SPEAKER_00 (07:46):
Right.
Which is wild because adiposetissue is historically viewed
just as passive energy storage,just blubber.
But Enai's work shows itactually acts as an endocrine
organ.
It controls the NAD plus levelsin your brain.
SPEAKER_01 (07:59):
Wait, really?
Body fat controls the brain?
SPEAKER_00 (08:01):
Specifically the hypothalamus, which is the
body's master control center.
The fat tissue secretes a vitalenzyme called EninMPT.
It packages this enzyme intothese tiny biological envelopes
called extracellular vesicles orEVs and ships them through the
bloodstream straight to thebrain.
SPEAKER_01 (08:18):
So that's like a care package.
SPEAKER_00 (08:19):
Exactly.
The brain receives these EVs anduses the enzyme inside to
manufacture its own NAD pluslocally.
SPEAKER_01 (08:27):
See, I have to push back on this because why would
the body design such aprecarious system?
I mean, relying on fat cells toconstantly ship enzymes to the
brain just to keep itfunctioning seems like a massive
single point of failure.
SPEAKER_00 (08:40):
It does sound risky.
SPEAKER_01 (08:41):
It's like the brain is outsourcing its critical
power plant machinery to like anexternal contractor.
SPEAKER_00 (08:47):
Right.
SPEAKER_01 (08:48):
Why not just make it all in-house?
SPEAKER_00 (08:49):
It looks like a vulnerability until you consider
energy allocation.
You see, the brain is anabsolute energy hog.
It consumes about 20% of thebody's total resources.
Right.
So by linking the brain's NADplus production to adipose
tissue, the body creates thisbrilliant feedback loop.
The fat tissue is essentiallytelling the brain, hey, we have
abundant healthy energy reservesdown here.
(09:10):
Keep the metabolism runninghigh, keep repairing the DNA.
SPEAKER_01 (09:13):
Oh, wow.
So it's a signal.
SPEAKER_00 (09:15):
Yes.
But as we age, or if that fattissue becomes highly
dysfunctional due to, say,metabolic disease, that shipping
network breaks down.
The brain's NAD plus drops, andthe brain signals the rest of
the body to slow down, whichaccelerates systemic aging.
SPEAKER_01 (09:31):
Aaron Powell That is fascinating.
We are basically just a constantnegotiation between our organs.
And looking at Joseph Bauer'sresearch from the University of
Pennsylvania, that negotiationactually extends to organisms
that aren't even human.
Trevor Burrus, Jr.
SPEAKER_00 (09:43):
The microbiome connection.
SPEAKER_01 (09:45):
Yeah.
He maps out this gut microbiomeloop that just blew my mind.
Our bodies actually secrete anNAD plus precursor nicotinamide
directly into our intestinaltract.
SPEAKER_00 (09:56):
Trevor Burrus Right.
We literally push it out intothe gut for our microbiome to
consume.
SPEAKER_01 (10:00):
So we feed them.
SPEAKER_00 (10:01):
We do.
And the gut bacteria processthat nicotinamide and excrete an
entirely different compoundcalled nicotinic acid.
SPEAKER_01 (10:08):
And then we take that back.
SPEAKER_00 (10:09):
Exactly.
Our host intestinal cells sweepup that nicotinic acid and use
it to synthesize NAD for us.
SPEAKER_01 (10:15):
It's like a mutually beneficial biological trade
agreement.
But why do the bacteria want ournicotinamide in the first place?
What's in it for them?
SPEAKER_00 (10:22):
Well, the microbiome needs to regulate its own local
environment.
The bacteria use our precursorsto manage their own metabolic
pathways so they can survive theharsh conditions of the human
gut.
Aaron Powell That makes sense.
And in doing so, they convert aprecursor we have in abundance
into a highly usable rawmaterial for us.
It creates incredible metabolicflexibility.
(10:44):
If your diet is lacking, yourgut bugs act as an outsourced
manufacturing plant.
SPEAKER_01 (10:49):
Aaron Powell But that also highlights a severe
modern risk, right?
I mean, if you obliterate yourmicrobiome with broad spectrum
antibiotics or a highlyprocessed diet, you aren't just
giving yourself an upsetstomach.
SPEAKER_00 (10:59):
No, you are actively shutting down a critical energy
manufacturing plant for yourcellular battery.
SPEAKER_01 (11:04):
Aaron Powell Which is terrifying.
Okay, so the system isincredibly intricate.
But we know the overarchingtrend.
As we age, those shippingnetworks slow down, the gut
efficiency drops, and oursystemic NAD plus levels just
fall.
SPEAKER_00 (11:16):
Right.
SPEAKER_01 (11:17):
Which brings us to the multi-billion dollar
question driving the clinicalside of these sources.
How do we effectively put NADplus back into the system?
Let's look at the actualdelivery methods.
SPEAKER_00 (11:28):
Well, the Santa Fe Mobile MD Clinic notes detail
the primary hurdle thatpharmacologists face, and that's
the bioavailability problem.
SPEAKER_01 (11:35):
Aaron Ross Powell Right.
Because you can't just swallow araw NAD plus pill, can you?
SPEAKER_00 (11:39):
You cannot.
The NAD plus molecule itself isphysically too large and too
unstable to survive thedigestive tract and enter the
bloodstream intact.
SPEAKER_01 (11:48):
Aaron Powell Which is why the oral supplement
industry relies entirely on theprecursors, you know, the
smaller building blocks like NRand NMN.
SPEAKER_00 (11:54):
Exactly.
But swallowing a precursor pillintroduces a new issue, the
first pass effect.
When you swallow an NR or NMNpill, it faces a gauntlet of
stomach acid.
SPEAKER_01 (12:06):
And even if it survives that.
SPEAKER_00 (12:07):
Right.
Whatever survives is routedstraight to the liver.
And the liver acts as a strictchemical checkpoint.
It metabolizes and breaks down amassive percentage of the
supplement before it everreaches your wider systemic
circulation.
SPEAKER_01 (12:19):
So you lose a vast amount of the active ingredient
almost immediately.
SPEAKER_00 (12:22):
You do, which is the exact reason IV therapy clinics
are booming right now.
By pushing NAD plus directlyinto a vein, you bypass the
stomach and the liver entirely.
You achieve 100%bioavailability.
SPEAKER_01 (12:35):
But reading the clinic's own operational
warnings from Santa Fe MobileMD, IV therapy is not just some
casual biohack you do on yourlunch break.
SPEAKER_00 (12:44):
Oh, not at all.
The physical sensation of arapid NAD plus infusion is
incredibly intense.
It causes severe chesttightness, nausea, and cramping.
SPEAKER_01 (12:54):
That sounds awful.
SPEAKER_00 (12:55):
Yeah, to mitigate that, clinics have to run the IV
drip very, very slowly, whichmeans you are tethered to an IV
pole for two to four hours.
SPEAKER_01 (13:05):
Plus it's super expensive.
SPEAKER_00 (13:06):
Exactly.
Combined with the high financialcost per session, it's a
significant barrier to entry forthe average person.
SPEAKER_01 (13:13):
So for the vast majority of you listening, daily
pills are realistically the onlyoption.
Which triggers basically themost common debate in the
longevity space online.
Nicotinamide robocyde, which isNR, versus nicotinamide
mononucleotide, which is NMN.
SPEAKER_00 (13:28):
The great precursor debate.
SPEAKER_01 (13:29):
Right.
Which precursor actually movesthe needle?
SPEAKER_00 (13:31):
Well, the Norwegian trial by researchers Dull and
Sulis provides some of the mostrigorous head-to-head human data
we currently have.
SPEAKER_01 (13:38):
What do they do?
SPEAKER_00 (13:38):
They took healthy middle-aged adults and
administered a high-dose 1200milligrams a day of either oral
NR or NMN for eight straightdays.
SPEAKER_01 (13:48):
And looking at the data tables from this trial, I
mean it wasn't even close.
NR basically blew NMN out of thewater in terms of blood
saturation.
SPEAKER_00 (13:56):
It did.
The NR group saw their blood NADplus levels spike by 161%,
whereas the NMN group only saw a69% increase.
SPEAKER_01 (14:05):
So NR was over twice as effective at boosting blood
levels.
SPEAKER_00 (14:09):
Right.
In the blood, NR is remarkablyefficient.
The compound is uniquely suitedto survive the digestive tract,
get taken up by cells, andconvert into NAD plus mock.
SPEAKER_01 (14:17):
But and this is a big but raising blood levels is
really only half the battle.
If we're talking aboutpreventing cognitive decline
and, you know, maintaining thathypothalamus control center we
talked about earlier, the bloodbrain barrier is notoriously
stubborn with molecules thissize.
SPEAKER_00 (14:31):
Oh, absolutely.
SPEAKER_01 (14:32):
So did these oral supplements actually make it to
the brain?
Because if it doesn't reach thebrain, are we just creating
really expensive blood?
SPEAKER_00 (14:39):
It's a great question.
In the initial eight-day windowof that Norwegian study, neither
NR nor NMN raised brain NAD pluslevels at all.
SPEAKER_01 (14:48):
Wow.
The scans showed a flat line inthe central nervous system.
SPEAKER_00 (14:52):
That has to be deeply discouraging for anyone
buying these supplements formental clarity.
SPEAKER_01 (14:56):
It is, but it highlights how aggressively the
brain defends its chemicalenvironment.
But and here's the good news theresearchers extended the NR
supplementation protocol to fourweeks.
SPEAKER_00 (15:06):
Okay, and what happened?
SPEAKER_01 (15:07):
After that sustained 28-day period, brain NAD plus
did significantly increase inthose healthy individuals.
SPEAKER_00 (15:13):
So it just takes time.
SPEAKER_01 (15:14):
Exactly.
Right.
It requires a sustainedsaturation of the blood to force
the uptake into the brain.
And we also see a lot ofvariability across studies.
For instance, a University ofPennsylvania trial showed that a
900 milligram dose of NR couldbump brain NAD plus by 16% in
just four hours.
SPEAKER_00 (15:33):
Wait, really?
In just four hours?
SPEAKER_01 (15:35):
Yes.
So the critical takeaway here isimmense individual variability.
Your absorption depends heavilyon your baseline deficiency, the
state of your gut microbiome,and your specific liver
function.
That makes a lot of sense.
So let's transition from justchanging numbers on a blood
panel to actual humanphysiology.
Does artificially raising yourNAD plus actually translate to
(15:56):
repairing disease and extendingfunctional health span?
SPEAKER_00 (15:59):
Aaron Ross Powell The clinical trials presented at
the NIH workshop focus exactlyon the how and why of these
interventions.
And the mechanisms are reallyfascinating.
SPEAKER_01 (16:07):
Aaron Powell Let's start with Douglas Seals at the
University of Colorado.
Yeah.
Because he demonstrated that NRsupplementation reduces systolic
blood pressure and aorticstiffness in older adults.
SPEAKER_00 (16:16):
Aaron Ross Powell Right.
And arterial stiffness is aprimary driver of cardiovascular
disease.
The mechanism here relies on theendothelial cells that line your
blood vessels.
Okay.
These cells use NAD plus to fuelthe enzymes that produce nitric
oxide.
And nitric oxide is a signalingmolecule that literally tells
the smooth muscle around yourarteries to relax and dilate.
SPEAKER_01 (16:37):
So as NAD plus levels fall with age.
SPEAKER_00 (16:39):
Exactly.
Nitric oxide production stallsand the blood vessels become
rigid.
Replenishing the NAD plusrestores that flexibility.
SPEAKER_01 (16:46):
That is huge.
And then you have Samuel Kleinat Washington University.
He conducted a 10-week placebocontrolled trial using NMN in
overweight prediabetic women,and he saw a 25% improvement in
muscle insulin sensitivity.
SPEAKER_00 (17:01):
Which is significant because insulin resistance often
begins in the mitochondria ofthe muscle tissue.
When muscle cells lack NAD plusalanel, their mitochondria
becomes sluggish.
SPEAKER_01 (17:12):
Like a weak battery.
SPEAKER_00 (17:13):
Exactly.
They become inefficient atoxidizing or burning glucose and
fatty acids.
So glucose backs up in thebloodstream.
By providing NMN, the musclemitochondria regain their
energetic capacity, clearingglucose from the blood much more
effectively.
SPEAKER_01 (17:28):
Okay, what about the brain?
Wilhelm Bohr from the NationalInstitute on Aging brought some
really interesting data onAlzheimer's models and
age-related hearing loss.
He focused heavily on a processcalled mitophagy.
SPEAKER_00 (17:39):
Right.
Mitophagy is essentially thecell taking out its own trash.
Dissective, old mitochondriaactually leak reactive oxygen
species.
They become highly toxic to thecell, particularly in
long-living cells like ourneurons.
SPEAKER_01 (17:51):
And how does NAD Plus help with that?
SPEAKER_00 (17:53):
NAD Plus acts as the signaling mechanism that tells
the cell to identify, dismantle,and clear out these defective
power plants before they causeneurodegeneration.
SPEAKER_01 (18:03):
It's like the cleanup crew.
Also, Schalender Bossin's dataon severe COVID-19 infections
was really striking.
He noted that the virusdramatically depletes systemic
NAD plus late.
SPEAKER_00 (18:15):
It does.
The immune cells basically burnthrough the body's battery
supply to mount an innate immuneresponse.
And that leaves the surroundingtissues starved of energy.
SPEAKER_01 (18:24):
So boosting the supply gives the immune system
the energy it needs to fightwithout compromising the rest of
the body.
SPEAKER_00 (18:30):
Exactly.
And to add one more, MichaelZamel presented a synergy study
showing that combining NAD plusprecursors with the amino acid
leucine massively increaseslipid oxidation, which is fat
burning in human cells, whilealso extending lifespan in worm
models.
SPEAKER_01 (18:46):
So the clinical evidence overwhelmingly supports
that this isn't just someanti-aging fad.
There are tangible, measurablephysiological mechanisms at play
here across cardiovascular,metabolic, and neurological
systems.
SPEAKER_00 (18:57):
Absolutely.
The science is very real.
SPEAKER_01 (18:59):
But, and this is my favorite part of the research we
looked at today, before anyonepulls out their credit card for
a$500 IV drip or a massive stackof precursor pills, there was a
study from the journal NatureAging, which was highlighted by
the Restore Hyperwellness Clinicthat fundamentally changes the
narrative of this entire field.
SPEAKER_00 (19:18):
It really reframes everything.
The researchers wanted tomeasure natural NED plus levels
in actual human muscle tissueacross different demographics.
SPEAKER_01 (19:27):
So they looked at young people versus older
people.
SPEAKER_00 (19:29):
Right.
And the baseline assumption heldtrue.
Young adults in their 20s and30s had robust levels, while the
general population of olderadults aged 65 to 80 showed
significant depletion.
SPEAKER_01 (19:41):
Which is exactly what we've been talking about.
But then they isolated aspecific cohort within that
older group.
SPEAKER_00 (19:46):
They did.
They found older individuals whoengaged in highly rigorous
physical activity.
We're talking clocking over13,000 steps a day and
completing three or more hoursof dedicated exercise a week.
SPEAKER_01 (19:57):
And when they tested the muscle tissue of these
highly active 65 to 80 yearolds, their NAD plus levels were
practically indistinguishablefrom the healthy 20 to 30 year
olds.
SPEAKER_00 (20:09):
It's incredible.
SPEAKER_01 (20:10):
I mean, so you're telling me that after all the
fierce academic debates, all theadvanced machine learning
frailty clocks, the big battleover supplement bioavailability,
the ultimate physiological cheatcoat is just putting on sneakers
and going for a walk.
SPEAKER_00 (20:23):
Basically, yes.
Because exercise is an intenseenergy stressor.
When you demand that level ofATP production from your
muscles, you force the body toheavily upregulate its internal
NAD plus synthesis and recyclingpathways.
SPEAKER_01 (20:38):
So the body adapts to the demand.
SPEAKER_00 (20:39):
Exactly.
Supplements and IV therapies arebasically just mimicking the
chemical state that physicalactivity creates naturally.
SPEAKER_01 (20:46):
They are tools to simulate the biological signal
of a long run or a heavy liftingsession.
SPEAKER_00 (20:50):
Right.
And they are incredibly valuablefor individuals who are
compromised, recovering fromillness, or just metabolically
unable to reach that level ofexertion.
SPEAKER_01 (20:59):
But for the general population listening to this, I
mean that is so empowering.
You don't necessarily need abiohacker budget to achieve
youthful cellular energy.
Your body possesses the fullmachinery required to maintain
these youthful levels, providedyou give it the mechanical
stimulus it evolved to handle.
SPEAKER_00 (21:16):
Yes.
We can really synthesize thisentire deep dive through that
lens.
NAD Plus is the undeniablecurrency of cellular life.
The scientific community isfiercely split on the
evolutionary why.
You know, Sinclair sees it as aketolongevity genes, Brenner
sees it as a vital stress repairfuel.
Right.
But the clinical application isuniversally promising.
(21:38):
Replenishing it improvesarterial flexibility, it clears
out toxic mitochondria, and itrestores insulin sensitivity.
SPEAKER_01 (21:45):
And if you're taking pills, NR currently shows a
distinct advantage over NMN inoral blood saturation, though it
does require weeks of consistentuse to cross the blood brain
barrier.
SPEAKER_00 (21:55):
But above all those pharmaceutical interventions,
your own physical activityremains the absolute Absolute
most potent regulator of thisentire system.
SPEAKER_01 (22:03):
I love that.
And you know, I want to leaveyou listening with just a
slightly different way toconceptualize this whole process
of growing older based oneverything we've unpacked today.
Because we are so conditioned toview aging as this relentless
ticking clock, a purelymechanical wearing down of our
joints and tissues.
SPEAKER_00 (22:21):
Aaron Powell Like the car engine running out of
oil.
SPEAKER_01 (22:23):
Exactly.
But look at the actual biologywe just discussed.
SPEAKER_00 (22:27):
If your body fat is literally packaging enzymes into
vesicles to ship to your brainto keep your metabolism awake,
and your gut microbiome istrading nicotinic acid with your
intestinal cells to keep yourcellular batteries charged.
Perhaps aging isn't just aninevitable, unstoppable physical
decay.
SPEAKER_01 (22:44):
Maybe it is a communication breakdown.
SPEAKER_00 (22:46):
It's dropped calls and lost shipments across this
vast decentralized cellularnetwork.
The signals between the fattissue, the brain, and the gut
just get weaker.
SPEAKER_01 (22:55):
And whether you choose to intervene through a
highly targeted NR supplement, aclinical IV therapy, we're
simply hitting 13,000 steps aday.
You aren't fighting anunstoppable clock.
You are just picking up thesignal again.
You are repairing thecommunication lines.
SPEAKER_00 (23:12):
Exactly.
You're just getting the networkback online.
SPEAKER_01 (23:14):
Recharging the battery so the screen doesn't go
dark at 2.0 PM.
Keep your signals strong, andwe'll catch you on the next deep
dive.
So when most of us buy a new smartphone, we
completely obsess over like allthe visible things, right?
SPEAKER_00 (00:05):
Yeah, the sleek glass, the camera lenses.
SPEAKER_01 (00:07):
Exactly.
How thin it is.
But we completely ignore thebattery.
I mean, at least until it's like2.0 p.m., your screen goes dark,
and suddenly literally nothingelse about the phone matters.
SPEAKER_00 (00:17):
Right.
Because the hardware is entirelyuseless without the charge.
SPEAKER_01 (00:20):
Right.
And the thing is, we treat ourbodies the exact same way.
We obsess over this surfacelevel aging.
So wrinkles, gray hair, losingmuscle tone while just
completely ignoring the cellularbattery that actually, you know,
powers our existence.
SPEAKER_00 (00:34):
Aaron Powell Yeah, we're so entirely focused on the
cosmetic symptoms.
Meanwhile, the true mechanism ofaging is happening quietly on
this microscopic energeticlevel.
SPEAKER_01 (00:44):
Aaron Powell Which brings us to what we're doing
today.
We are taking a deep dive intothe raw science of that cellular
battery, a molecule called NADplus ornato or uh nicotinamide
adenine to nucleotide.
SPEAKER_00 (00:56):
Always a mouthful.
SPEAKER_01 (00:57):
Yeah, truly.
But we've got a massive stack ofsources today to help us just
cut through the multi-billiondollar hype of the whole
anti-aging industry.
SPEAKER_00 (01:05):
And the sources are fantastic.
We're looking at the highlycomprehensive 2021 National
Institutes of Health workshoptranscripts.
SPEAKER_01 (01:13):
Right, featuring literally the pioneers of aging
research.
Plus, we've got a historicalreview from the journal Cell
Metabolism, some really freshclinical trial data, and even
the operational notes from anactual IV therapy clinic, Santa
Fe Mobile MD.
SPEAKER_00 (01:28):
So we're really covering it from the theoretical
lab work all the way to theclinical application.
SPEAKER_01 (01:33):
Exactly.
Our mission for you listening isto basically bypass all those
flashy supplement ads you seeonline and figure out the actual
biology.
Because looking at these NIHworkshop transcripts, man, these
researchers are practically ateach other's throats.
SPEAKER_00 (01:47):
It is a phenomenal clash of perspectives, honestly.
But you know, to reallyunderstand why they're arguing,
we first have to look at whatNAD plus physically does in your
body.
SPEAKER_01 (01:55):
Right.
Let's lay the groundwork.
SPEAKER_00 (01:57):
At its core, it's what we call a coenzyme.
So it's this fundamental helpermolecule that is literally found
in every single living cell.
It acts as the essentialdelivery truck for cellular
energy.
SPEAKER_01 (02:09):
So when you eat a meal, right.
SPEAKER_00 (02:10):
When you eat, NAD Plus is absolutely required to
convert the nutrients from yourfood into ATP.
And ATP is the actual chemicalcurrency your cells spend to
keep your heart beating, to keepyou breathing.
SPEAKER_01 (02:22):
So without NAD Plus, your biology simply halts.
It's like the ultimatebiological spark plug.
SPEAKER_00 (02:28):
Exactly.
But it's the secondary role ofNAD Plus that actually triggered
this whole massive longevityindustry.
It fuels the enzymes that repairdamaged DNA.
SPEAKER_01 (02:37):
And looking at that cell metabolism historical
review, the trajectory of how wediscovered this is just wild.
SPEAKER_00 (02:44):
Oh, it really is.
It spans over a century.
SPEAKER_01 (02:46):
Yeah.
It starts back in 1906 withthese two researchers, Harden
and Young, and they wereliterally just studying yeast
fermentation for brewing.
SPEAKER_00 (02:53):
Right, a very different application.
SPEAKER_01 (02:54):
And then cut to 1949, scientist Conrad Elvium
links the NAD plus precursor,which is vitamin B3, to curing
Pellagra, which was thishorrific fatal disease.
SPEAKER_00 (03:06):
Right, characterized by dermatitis and severe
dementia.
SPEAKER_01 (03:09):
Yeah, and they initially studied it as black
tongue in dogs, which is crazyto think about.
SPEAKER_00 (03:13):
It really is.
And, you know, the jump frombrewing yeast and canine
pellagra to human longevity,that took decades.
SPEAKER_01 (03:20):
Decades.
So when did the paradigmactually shift?
SPEAKER_00 (03:23):
Aaron Ross Powell That would be around the year
2000.
Leonard Garante and ShinichiroImai made this truly monumental
connection.
They discovered that NAD plus isthe mandatory fuel for a class
of proteins called sirtuins.
SPEAKER_01 (03:37):
Sirtuins, you hear that word a lot in biohacking
circles.
SPEAKER_00 (03:40):
Oh, constantly.
Because sirtuins essentially actas your cellular guardians.
They repair DNA, they manageinflammation, they regulate your
metabolic health.
But and this is the key, theyare completely NAD dependent.
SPEAKER_01 (03:51):
Aaron Powell So they need the battery to run.
SPEAKER_00 (03:53):
Aaron Powell Exactly.
And the problem is as we age,our NAD plus supply just
plummets, which means theseguardians are essentially
starved of the fuel they need toactually protect us.
SPEAKER_01 (04:02):
Aaron Powell Okay.
Which brings us to thisheavyweight bout in the NIH
workshop notes.
Because there's a massive fightover how these sertuans actually
fit into the whole agingprocess.
SPEAKER_00 (04:10):
Aaron Powell Yeah, it gets quite heated.
SPEAKER_01 (04:12):
Aaron Powell David Sinclair from Harvard University
presented some incrediblyaggressive data here.
I mean he's arguing thatsertuans are dedicated longevity
genes.
SPEAKER_00 (04:20):
Aaron Powell Right, that they are explicitly
designed to keep us young.
SPEAKER_01 (04:23):
Exactly.
And he showed that supplementingmice with an NAD plus precursor,
NMN, dramatically improves theirmetabolic health.
He even uses these machinelearning algorithms.
They're called the FRIT andAFARAID clocks.
SPEAKER_00 (04:37):
Clever acronyms in this field.
SPEAKER_01 (04:38):
Very clever.
It stands for Frailty InferredGeriatric Health Timeline.
And he yells them to show thatchronic NMN treatment actually
lowers frailty scores in miceand predicts a longer lifespan.
He's basically framing NED plusas the key to just turning these
longevity genes back on.
SPEAKER_00 (04:56):
So Sinclair's whole narrative is that we have this
ancient survival circuit insideus that we can biohack.
SPEAKER_01 (05:01):
Right.
But then Charles Brenner fromThe City of Hope steps up and he
essentially just throws agrenade at that entire premise.
SPEAKER_00 (05:07):
He really does.
I mean, his abstract bluntlystates, and I quote, 99% of what
you've been told about Sirtuansand longevity is wrong.
SPEAKER_01 (05:15):
Yeah, he calls the global focus on Sirtuans as
longevity regulatorsintellectually bankrupt.
Which, I mean, that is notstandard academic politeness.
SPEAKER_00 (05:25):
Not at all.
Brenner is arguing from a verystrict evolutionary biology
perspective here.
His main point is that animalswere never evolutionarily
selected to have genes dedicatedto making them live longer.
SPEAKER_01 (05:37):
Because evolution only cares about reproduction.
SPEAKER_00 (05:39):
Exactly.
Evolution only selects fortraits that help you survive
long enough to reproduce andraise your young.
Once you've done that, strictlyspeaking, you are biologically
dispensable.
SPEAKER_01 (05:49):
Wow, harsh reality.
SPEAKER_00 (05:51):
It is.
So from that view, allocatingprecious cellular energy to
keeping a post-reproductiveorganism young, that would
actually be a severeevolutionary disadvantage.
SPEAKER_01 (05:59):
So what does Brenner think NAD Plus is doing then?
SPEAKER_00 (06:02):
He argues that NAD Plus and Sirtuans aren't these
magical anti-aging switches.
They're simply part of a stressresponse system.
It's just the fuel our cells useto repair the daily, unavoidable
damage caused by metabolizingfood and fighting off pathogens.
SPEAKER_01 (06:17):
Okay, I want to neutrally frame this debate for
anyone trying to make sense ofthe science, because we're not
taking sides here.
And both of these guys havebrilliant researchers behind
them.
SPEAKER_00 (06:27):
Absolutely.
SPEAKER_01 (06:27):
Let's think of NAD Plus as the oil in your car's
engine.
Sinclair is arguing that thisspecific oil interacts with this
hidden high-tech computer chipin the car, the Sirtuans, that
actually reverses the age of theengine components.
SPEAKER_00 (06:41):
Right.
SPEAKER_01 (06:41):
But Brenner is arguing that no, there is no
magic computer chip.
The oil simply stops the pistonsfrom grinding together and
seizing up when you push theengine too hard.
SPEAKER_00 (06:51):
That's a great way to put it.
SPEAKER_01 (06:52):
But regardless of the underlying mechanism,
whether it's unlocking truelongevity or just mitigating
stress, both camps absolutelyagree on one thing.
If your car runs out of oil, theengine dies.
You need the NAD plus NITUS.
SPEAKER_00 (07:04):
Yes.
The absolute consensus at theworkshop, despite all those
fiery disagreements onevolutionary intent, is that
replenishing the NAD plusmetabolome is highly beneficial
for maintaining tissue health.
SPEAKER_01 (07:16):
But the way our tissues actually manage that
supply, that is where thebiology gets genuinely strange.
Because you would assume amolecule this critical would
just be hoarded by everyindividual cell, right?
Every cell for itself.
SPEAKER_00 (07:28):
You would think so.
But Shinichiro Imai's researchoutlines something he calls the
NAD World 3.0, and it revealsthis highly complex,
decentralized communicationnetwork across your entire body.
SPEAKER_01 (07:41):
And the boss of this whole network is your adipose
tissue, which is essentiallyyour body fat.
SPEAKER_00 (07:46):
Right.
Which is wild because adiposetissue is historically viewed
just as passive energy storage,just blubber.
But Enai's work shows itactually acts as an endocrine
organ.
It controls the NAD plus levelsin your brain.
SPEAKER_01 (07:59):
Wait, really?
Body fat controls the brain?
SPEAKER_00 (08:01):
Specifically the hypothalamus, which is the
body's master control center.
The fat tissue secretes a vitalenzyme called EninMPT.
It packages this enzyme intothese tiny biological envelopes
called extracellular vesicles orEVs and ships them through the
bloodstream straight to thebrain.
SPEAKER_01 (08:18):
So that's like a care package.
SPEAKER_00 (08:19):
Exactly.
The brain receives these EVs anduses the enzyme inside to
manufacture its own NAD pluslocally.
SPEAKER_01 (08:27):
See, I have to push back on this because why would
the body design such aprecarious system?
I mean, relying on fat cells toconstantly ship enzymes to the
brain just to keep itfunctioning seems like a massive
single point of failure.
SPEAKER_00 (08:40):
It does sound risky.
SPEAKER_01 (08:41):
It's like the brain is outsourcing its critical
power plant machinery to like anexternal contractor.
SPEAKER_00 (08:47):
Right.
SPEAKER_01 (08:48):
Why not just make it all in-house?
SPEAKER_00 (08:49):
It looks like a vulnerability until you consider
energy allocation.
You see, the brain is anabsolute energy hog.
It consumes about 20% of thebody's total resources.
Right.
So by linking the brain's NADplus production to adipose
tissue, the body creates thisbrilliant feedback loop.
The fat tissue is essentiallytelling the brain, hey, we have
abundant healthy energy reservesdown here.
(09:10):
Keep the metabolism runninghigh, keep repairing the DNA.
SPEAKER_01 (09:13):
Oh, wow.
So it's a signal.
SPEAKER_00 (09:15):
Yes.
But as we age, or if that fattissue becomes highly
dysfunctional due to, say,metabolic disease, that shipping
network breaks down.
The brain's NAD plus drops, andthe brain signals the rest of
the body to slow down, whichaccelerates systemic aging.
SPEAKER_01 (09:31):
Aaron Powell That is fascinating.
We are basically just a constantnegotiation between our organs.
And looking at Joseph Bauer'sresearch from the University of
Pennsylvania, that negotiationactually extends to organisms
that aren't even human.
Trevor Burrus, Jr.
SPEAKER_00 (09:43):
The microbiome connection.
SPEAKER_01 (09:45):
Yeah.
He maps out this gut microbiomeloop that just blew my mind.
Our bodies actually secrete anNAD plus precursor nicotinamide
directly into our intestinaltract.
SPEAKER_00 (09:56):
Trevor Burrus Right.
We literally push it out intothe gut for our microbiome to
consume.
SPEAKER_01 (10:00):
So we feed them.
SPEAKER_00 (10:01):
We do.
And the gut bacteria processthat nicotinamide and excrete an
entirely different compoundcalled nicotinic acid.
SPEAKER_01 (10:08):
And then we take that back.
SPEAKER_00 (10:09):
Exactly.
Our host intestinal cells sweepup that nicotinic acid and use
it to synthesize NAD for us.
SPEAKER_01 (10:15):
It's like a mutually beneficial biological trade
agreement.
But why do the bacteria want ournicotinamide in the first place?
What's in it for them?
SPEAKER_00 (10:22):
Well, the microbiome needs to regulate its own local
environment.
The bacteria use our precursorsto manage their own metabolic
pathways so they can survive theharsh conditions of the human
gut.
Aaron Powell That makes sense.
And in doing so, they convert aprecursor we have in abundance
into a highly usable rawmaterial for us.
It creates incredible metabolicflexibility.
(10:44):
If your diet is lacking, yourgut bugs act as an outsourced
manufacturing plant.
SPEAKER_01 (10:49):
Aaron Powell But that also highlights a severe
modern risk, right?
I mean, if you obliterate yourmicrobiome with broad spectrum
antibiotics or a highlyprocessed diet, you aren't just
giving yourself an upsetstomach.
SPEAKER_00 (10:59):
No, you are actively shutting down a critical energy
manufacturing plant for yourcellular battery.
SPEAKER_01 (11:04):
Aaron Powell Which is terrifying.
Okay, so the system isincredibly intricate.
But we know the overarchingtrend.
As we age, those shippingnetworks slow down, the gut
efficiency drops, and oursystemic NAD plus levels just
fall.
SPEAKER_00 (11:16):
Right.
SPEAKER_01 (11:17):
Which brings us to the multi-billion dollar
question driving the clinicalside of these sources.
How do we effectively put NADplus back into the system?
Let's look at the actualdelivery methods.
SPEAKER_00 (11:28):
Well, the Santa Fe Mobile MD Clinic notes detail
the primary hurdle thatpharmacologists face, and that's
the bioavailability problem.
SPEAKER_01 (11:35):
Aaron Ross Powell Right.
Because you can't just swallow araw NAD plus pill, can you?
SPEAKER_00 (11:39):
You cannot.
The NAD plus molecule itself isphysically too large and too
unstable to survive thedigestive tract and enter the
bloodstream intact.
SPEAKER_01 (11:48):
Aaron Powell Which is why the oral supplement
industry relies entirely on theprecursors, you know, the
smaller building blocks like NRand NMN.
SPEAKER_00 (11:54):
Exactly.
But swallowing a precursor pillintroduces a new issue, the
first pass effect.
When you swallow an NR or NMNpill, it faces a gauntlet of
stomach acid.
SPEAKER_01 (12:06):
And even if it survives that.
SPEAKER_00 (12:07):
Right.
Whatever survives is routedstraight to the liver.
And the liver acts as a strictchemical checkpoint.
It metabolizes and breaks down amassive percentage of the
supplement before it everreaches your wider systemic
circulation.
SPEAKER_01 (12:19):
So you lose a vast amount of the active ingredient
almost immediately.
SPEAKER_00 (12:22):
You do, which is the exact reason IV therapy clinics
are booming right now.
By pushing NAD plus directlyinto a vein, you bypass the
stomach and the liver entirely.
You achieve 100%bioavailability.
SPEAKER_01 (12:35):
But reading the clinic's own operational
warnings from Santa Fe MobileMD, IV therapy is not just some
casual biohack you do on yourlunch break.
SPEAKER_00 (12:44):
Oh, not at all.
The physical sensation of arapid NAD plus infusion is
incredibly intense.
It causes severe chesttightness, nausea, and cramping.
SPEAKER_01 (12:54):
That sounds awful.
SPEAKER_00 (12:55):
Yeah, to mitigate that, clinics have to run the IV
drip very, very slowly, whichmeans you are tethered to an IV
pole for two to four hours.
SPEAKER_01 (13:05):
Plus it's super expensive.
SPEAKER_00 (13:06):
Exactly.
Combined with the high financialcost per session, it's a
significant barrier to entry forthe average person.
SPEAKER_01 (13:13):
So for the vast majority of you listening, daily
pills are realistically the onlyoption.
Which triggers basically themost common debate in the
longevity space online.
Nicotinamide robocyde, which isNR, versus nicotinamide
mononucleotide, which is NMN.
SPEAKER_00 (13:28):
The great precursor debate.
SPEAKER_01 (13:29):
Right.
Which precursor actually movesthe needle?
SPEAKER_00 (13:31):
Well, the Norwegian trial by researchers Dull and
Sulis provides some of the mostrigorous head-to-head human data
we currently have.
SPEAKER_01 (13:38):
What do they do?
SPEAKER_00 (13:38):
They took healthy middle-aged adults and
administered a high-dose 1200milligrams a day of either oral
NR or NMN for eight straightdays.
SPEAKER_01 (13:48):
And looking at the data tables from this trial, I
mean it wasn't even close.
NR basically blew NMN out of thewater in terms of blood
saturation.
SPEAKER_00 (13:56):
It did.
The NR group saw their blood NADplus levels spike by 161%,
whereas the NMN group only saw a69% increase.
SPEAKER_01 (14:05):
So NR was over twice as effective at boosting blood
levels.
SPEAKER_00 (14:09):
Right.
In the blood, NR is remarkablyefficient.
The compound is uniquely suitedto survive the digestive tract,
get taken up by cells, andconvert into NAD plus mock.
SPEAKER_01 (14:17):
But and this is a big but raising blood levels is
really only half the battle.
If we're talking aboutpreventing cognitive decline
and, you know, maintaining thathypothalamus control center we
talked about earlier, the bloodbrain barrier is notoriously
stubborn with molecules thissize.
SPEAKER_00 (14:31):
Oh, absolutely.
SPEAKER_01 (14:32):
So did these oral supplements actually make it to
the brain?
Because if it doesn't reach thebrain, are we just creating
really expensive blood?
SPEAKER_00 (14:39):
It's a great question.
In the initial eight-day windowof that Norwegian study, neither
NR nor NMN raised brain NAD pluslevels at all.
SPEAKER_01 (14:48):
Wow.
The scans showed a flat line inthe central nervous system.
SPEAKER_00 (14:52):
That has to be deeply discouraging for anyone
buying these supplements formental clarity.
SPEAKER_01 (14:56):
It is, but it highlights how aggressively the
brain defends its chemicalenvironment.
But and here's the good news theresearchers extended the NR
supplementation protocol to fourweeks.
SPEAKER_00 (15:06):
Okay, and what happened?
SPEAKER_01 (15:07):
After that sustained 28-day period, brain NAD plus
did significantly increase inthose healthy individuals.
SPEAKER_00 (15:13):
So it just takes time.
SPEAKER_01 (15:14):
Exactly.
Right.
It requires a sustainedsaturation of the blood to force
the uptake into the brain.
And we also see a lot ofvariability across studies.
For instance, a University ofPennsylvania trial showed that a
900 milligram dose of NR couldbump brain NAD plus by 16% in
just four hours.
SPEAKER_00 (15:33):
Wait, really?
In just four hours?
SPEAKER_01 (15:35):
Yes.
So the critical takeaway here isimmense individual variability.
Your absorption depends heavilyon your baseline deficiency, the
state of your gut microbiome,and your specific liver
function.
That makes a lot of sense.
So let's transition from justchanging numbers on a blood
panel to actual humanphysiology.
Does artificially raising yourNAD plus actually translate to
(15:56):
repairing disease and extendingfunctional health span?
SPEAKER_00 (15:59):
Aaron Ross Powell The clinical trials presented at
the NIH workshop focus exactlyon the how and why of these
interventions.
And the mechanisms are reallyfascinating.
SPEAKER_01 (16:07):
Aaron Powell Let's start with Douglas Seals at the
University of Colorado.
Yeah.
Because he demonstrated that NRsupplementation reduces systolic
blood pressure and aorticstiffness in older adults.
SPEAKER_00 (16:16):
Aaron Ross Powell Right.
And arterial stiffness is aprimary driver of cardiovascular
disease.
The mechanism here relies on theendothelial cells that line your
blood vessels.
Okay.
These cells use NAD plus to fuelthe enzymes that produce nitric
oxide.
And nitric oxide is a signalingmolecule that literally tells
the smooth muscle around yourarteries to relax and dilate.
SPEAKER_01 (16:37):
So as NAD plus levels fall with age.
SPEAKER_00 (16:39):
Exactly.
Nitric oxide production stallsand the blood vessels become
rigid.
Replenishing the NAD plusrestores that flexibility.
SPEAKER_01 (16:46):
That is huge.
And then you have Samuel Kleinat Washington University.
He conducted a 10-week placebocontrolled trial using NMN in
overweight prediabetic women,and he saw a 25% improvement in
muscle insulin sensitivity.
SPEAKER_00 (17:01):
Which is significant because insulin resistance often
begins in the mitochondria ofthe muscle tissue.
When muscle cells lack NAD plusalanel, their mitochondria
becomes sluggish.
SPEAKER_01 (17:12):
Like a weak battery.
SPEAKER_00 (17:13):
Exactly.
They become inefficient atoxidizing or burning glucose and
fatty acids.
So glucose backs up in thebloodstream.
By providing NMN, the musclemitochondria regain their
energetic capacity, clearingglucose from the blood much more
effectively.
SPEAKER_01 (17:28):
Okay, what about the brain?
Wilhelm Bohr from the NationalInstitute on Aging brought some
really interesting data onAlzheimer's models and
age-related hearing loss.
He focused heavily on a processcalled mitophagy.
SPEAKER_00 (17:39):
Right.
Mitophagy is essentially thecell taking out its own trash.
Dissective, old mitochondriaactually leak reactive oxygen
species.
They become highly toxic to thecell, particularly in
long-living cells like ourneurons.
SPEAKER_01 (17:51):
And how does NAD Plus help with that?
SPEAKER_00 (17:53):
NAD Plus acts as the signaling mechanism that tells
the cell to identify, dismantle,and clear out these defective
power plants before they causeneurodegeneration.
SPEAKER_01 (18:03):
It's like the cleanup crew.
Also, Schalender Bossin's dataon severe COVID-19 infections
was really striking.
He noted that the virusdramatically depletes systemic
NAD plus late.
SPEAKER_00 (18:15):
It does.
The immune cells basically burnthrough the body's battery
supply to mount an innate immuneresponse.
And that leaves the surroundingtissues starved of energy.
SPEAKER_01 (18:24):
So boosting the supply gives the immune system
the energy it needs to fightwithout compromising the rest of
the body.
SPEAKER_00 (18:30):
Exactly.
And to add one more, MichaelZamel presented a synergy study
showing that combining NAD plusprecursors with the amino acid
leucine massively increaseslipid oxidation, which is fat
burning in human cells, whilealso extending lifespan in worm
models.
SPEAKER_01 (18:46):
So the clinical evidence overwhelmingly supports
that this isn't just someanti-aging fad.
There are tangible, measurablephysiological mechanisms at play
here across cardiovascular,metabolic, and neurological
systems.
SPEAKER_00 (18:57):
Absolutely.
The science is very real.
SPEAKER_01 (18:59):
But, and this is my favorite part of the research we
looked at today, before anyonepulls out their credit card for
a$500 IV drip or a massive stackof precursor pills, there was a
study from the journal NatureAging, which was highlighted by
the Restore Hyperwellness Clinicthat fundamentally changes the
narrative of this entire field.
SPEAKER_00 (19:18):
It really reframes everything.
The researchers wanted tomeasure natural NED plus levels
in actual human muscle tissueacross different demographics.
SPEAKER_01 (19:27):
So they looked at young people versus older
people.
SPEAKER_00 (19:29):
Right.
And the baseline assumption heldtrue.
Young adults in their 20s and30s had robust levels, while the
general population of olderadults aged 65 to 80 showed
significant depletion.
SPEAKER_01 (19:41):
Which is exactly what we've been talking about.
But then they isolated aspecific cohort within that
older group.
SPEAKER_00 (19:46):
They did.
They found older individuals whoengaged in highly rigorous
physical activity.
We're talking clocking over13,000 steps a day and
completing three or more hoursof dedicated exercise a week.
SPEAKER_01 (19:57):
And when they tested the muscle tissue of these
highly active 65 to 80 yearolds, their NAD plus levels were
practically indistinguishablefrom the healthy 20 to 30 year
olds.
SPEAKER_00 (20:09):
It's incredible.
SPEAKER_01 (20:10):
I mean, so you're telling me that after all the
fierce academic debates, all theadvanced machine learning
frailty clocks, the big battleover supplement bioavailability,
the ultimate physiological cheatcoat is just putting on sneakers
and going for a walk.
SPEAKER_00 (20:23):
Basically, yes.
Because exercise is an intenseenergy stressor.
When you demand that level ofATP production from your
muscles, you force the body toheavily upregulate its internal
NAD plus synthesis and recyclingpathways.
SPEAKER_01 (20:38):
So the body adapts to the demand.
SPEAKER_00 (20:39):
Exactly.
Supplements and IV therapies arebasically just mimicking the
chemical state that physicalactivity creates naturally.
SPEAKER_01 (20:46):
They are tools to simulate the biological signal
of a long run or a heavy liftingsession.
SPEAKER_00 (20:50):
Right.
And they are incredibly valuablefor individuals who are
compromised, recovering fromillness, or just metabolically
unable to reach that level ofexertion.
SPEAKER_01 (20:59):
But for the general population listening to this, I
mean that is so empowering.
You don't necessarily need abiohacker budget to achieve
youthful cellular energy.
Your body possesses the fullmachinery required to maintain
these youthful levels, providedyou give it the mechanical
stimulus it evolved to handle.
SPEAKER_00 (21:16):
Yes.
We can really synthesize thisentire deep dive through that
lens.
NAD Plus is the undeniablecurrency of cellular life.
The scientific community isfiercely split on the
evolutionary why.
You know, Sinclair sees it as aketolongevity genes, Brenner
sees it as a vital stress repairfuel.
Right.
But the clinical application isuniversally promising.
(21:38):
Replenishing it improvesarterial flexibility, it clears
out toxic mitochondria, and itrestores insulin sensitivity.
SPEAKER_01 (21:45):
And if you're taking pills, NR currently shows a
distinct advantage over NMN inoral blood saturation, though it
does require weeks of consistentuse to cross the blood brain
barrier.
SPEAKER_00 (21:55):
But above all those pharmaceutical interventions,
your own physical activityremains the absolute Absolute
most potent regulator of thisentire system.
SPEAKER_01 (22:03):
I love that.
And you know, I want to leaveyou listening with just a
slightly different way toconceptualize this whole process
of growing older based oneverything we've unpacked today.
Because we are so conditioned toview aging as this relentless
ticking clock, a purelymechanical wearing down of our
joints and tissues.
SPEAKER_00 (22:21):
Aaron Powell Like the car engine running out of
oil.
SPEAKER_01 (22:23):
Exactly.
But look at the actual biologywe just discussed.
SPEAKER_00 (22:27):
If your body fat is literally packaging enzymes into
vesicles to ship to your brainto keep your metabolism awake,
and your gut microbiome istrading nicotinic acid with your
intestinal cells to keep yourcellular batteries charged.
Perhaps aging isn't just aninevitable, unstoppable physical
decay.
SPEAKER_01 (22:44):
Maybe it is a communication breakdown.
SPEAKER_00 (22:46):
It's dropped calls and lost shipments across this
vast decentralized cellularnetwork.
The signals between the fattissue, the brain, and the gut
just get weaker.
SPEAKER_01 (22:55):
And whether you choose to intervene through a
highly targeted NR supplement, aclinical IV therapy, we're
simply hitting 13,000 steps aday.
You aren't fighting anunstoppable clock.
You are just picking up thesignal again.
You are repairing thecommunication lines.
SPEAKER_00 (23:12):
Exactly.
You're just getting the networkback online.
SPEAKER_01 (23:14):
Recharging the battery so the screen doesn't go
dark at 2.0 PM.
Keep your signals strong, andwe'll catch you on the next deep
dive.
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