Why NAD+ Drops With Age And What The Science Says About NMN And NR

We track the real biology behind the NAD+ craze, from how cells turn food into energy to why that energy system breaks down with age. We also weigh what NMN and NR actually do in human trials against what marketing claims they do, including the messy roles of CD38 and the gut microbiome. 
• NAD+ as an electron carrier that powers ATP production 
• Mitochondrial dysfunction as NAD+ declines with age 
• Sirtuins as NAD+-dependent regulators of repair and stress responses 
• Why “sirtfood” claims collapse on dose and bioavailability 
• The failed PARP1 explanation and the disposable soma theory 
• CD38 as an NADase that rises with age 
• Knockout and overexpression studies that point to causation 
• Why oral NAD+ cannot raise intracellular NAD+ directly 
• NR and NMN as precursors using salvage pathways and transporters 
• CD38 degrading precursors in vivo and acting as an ectoenzyme 
• What 2025–2026 human clinical trials show on safety and biomarkers 
• Muscle biopsy paradox of unchanged steady-state NAD+ 
• Metabolic flux, species differences, and why humans are not mice 
• Microbiome conversion of NR into niacin and the NAAD signal 
• Conflicts of interest, surrogate markers versus real clinical endpoints 
• Supplement purity problems and the theoretical cancer-fueling risk 
• Why CD38 inhibitors may be a better long-term target than higher dosing 

This podcast is created by Ai for educational and entertainment purposes only and does not constitute professional medical or health advice. Please talk to your healthcare team for medical advice. 

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Transcript

The Cellular Battery Metaphor

SPEAKER_01 0:00

I want you to imagine something for a second. Imagine if your cells. Uh every single one of the trillions of microsopic cells keeping you alive right now had a tiny battery indicator floating right above them.

SPEAKER_00 0:13

Like exactly what you see in the top right corner of your phone screen.

SPEAKER_01 0:16

Yes, exactly like that. And you know, when you're a kid, that battery is just pegged at 100%. It is bright solid green. Right. You can run around a playground all day, scrape your knee, bounce back the next morning, and your internal machinery just hums along. But as you get older, that little battery icon starts draining. It drops to 80%, then 50%. And eventually, somewhere in middle age, it starts blinking that terrifying, anxious, flashing red.

SPEAKER_00 0:44

Which is honestly a very visceral way to visualize chronological aging versus biological aging. Trevor Burrus, Jr.

SPEAKER_01 0:50

It's the worst feeling when your phone does it, and it's worse when your body does it. You know, your energy dips, your muscles just don't recover after a workout, your focus blurs. The fundamental machinery of your body just sort of it grinds down.

SPEAKER_00 1:02

Aaron Powell And that blinking red battery isn't just a metaphor, it is the exact biological mechanism we are unpacking for today's deep dive. Because that cellular battery is powered by a very real, very heavily researched molecule called NAD plus Nair.

SPEAKER_01 1:19

Right. NAD plus C, which stands for nicotinamide adenine dinucleotide.

SPEAKER_00 1:25

Right. You nailed the pronunciation.

SPEAKER_01 1:26

Thank you. I practiced. But seriously, I mean, I can't even open my phone lately without seeing a tech billionaire or some fitness influencer trying to sell me a pill that supposedly boosts this stuff. The obsession is just everywhere.

SPEAKER_00 1:38

It really is. It sits at the absolute center of the modern anti-aging industry, but uh more importantly, it sits at the center of the human aging process itself.

SPEAKER_01 1:47

Yeah.

SPEAKER_00 1:48

So today we are going to cut straight through the marketing campaigns. We have a massive stack of scientific literature in front of us.

SPEAKER_01 1:53

Well, it is a mountain of papers.

SPEAKER_00 1:55

Literally. We've got clinical reviews from 2025 and 2026, deep cellular biology studies, metabolic profiles. And our mission today is to look at exactly what happens inside human cells when that battery drains.

SPEAKER_01 2:07

Because the hype right now is completely unhinged. You have entire supplement empires built overnight, people claiming they've found the literal cure for aging, and you know, consumers spending billions on NAD plus precursors like NMN and NR.

SPEAKER_00 2:20

Aaron Powell Which is why we need to separate the genuine, fascinating cellular biology from the frankly dangerous commercial hype. The transition from we reversed aging in a laboratory mouse to this pill works in complex human beings is incredibly fraught.

SPEAKER_01 2:37

So fraught. Let's unpack the actual biology first, because before we can understand why we're

What NAD+ Actually Does

SPEAKER_01 2:42

losing our vitality, we really need to understand what powers it in the first place.

SPEAKER_00 2:45

Exactly.

SPEAKER_01 2:46

So uh NAD plus gas, the battery fluid, what exactly is this molecule doing inside of us?

SPEAKER_00 2:52

Aaron Ross Powell Well, at its core, NAD plus is an essential coenzyme for energy production. You can kind of think of it as a biological shuttle bus. Aaron Powell A shuttle bus? For what? For electrons. It is absolutely critical for the fundamental metabolic processes. And I'm talking about the foundational mechanics of keeping a mammal alive. Things like glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation.

SPEAKER_01 3:14

Okay, wait, hold on. Let's not lose anyone in the biochemistry right out of the gate. Let's break those down. Glycolysis is just, I mean, that's just breaking down sugar, right?

SPEAKER_00 3:23

Basically, yes. Glycolysis literally means splitting sugar. When you eat a carbohydrate, it enters the cell and an enzymatic process splits that glucose molecule to extract energy. Right. But to do that, the cell needs to move electrons around. This involves what we call redox reactions.

SPEAKER_01 3:41

Redox, meaning reduction and oxidation.

SPEAKER_00 3:44

Precisely. Oxidation is when a molecule loses an electron, and reduction is when a molecule gains an electron. NAD plus is the molecule that swoops in, grabs those high-energy electrons from the sugar you ate. Which reduces the NAD plus it into a form called NADH, and then it acts as that shuttle bus, physically carrying those electrons to the mitochondria.

SPEAKER_01 4:04

Aaron Powell, so it's literally like a microscopic dump truck just moving energy from my breakfast into my cellular engines.

SPEAKER_00 4:10

Aaron Powell That is exactly what it is. And once it drops off those electrons at the mitochondria, it powers that third process I mentioned, oxidative phosphorylation.

SPEAKER_01 4:18

That's a mouthful.

SPEAKER_00 4:19

It is, but it's just the actual assembly line inside your mitochondria where ATP is generated.

SPEAKER_01 4:23

Aaron Powell And ATP is the energy currency.

SPEAKER_00 4:25

Right. The chemical energy currency your body uses to contract muscles, fire neurons, keep your heart beating.

SPEAKER_01 4:30

So to put it in completely different terms, uh I want you to imagine your body is this massive, high-tech, smart home.

SPEAKER_00 4:38

Okay, like this.

SPEAKER_01 4:39

Without NAD plus show, it's like the electrical grid just goes offline. Right. Without that physical carrier moving the electrons, the lights, which are your mitochondria, they just flicker and die. The security system, which would be your DNA repair mechanisms, it completely shuts down. The whole house just goes dark.

SPEAKER_00 4:56

Aaron Powell That is a highly accurate analogy. Because in healthy cells, the entire respiration-driving ADP synthesis relies entirely on the ratio between the empty dump trucks. And NAD plus NADH. When your NAD plus levels decline, the transport system halts. That leads directly to mitochondrial dysfunction.

SPEAKER_01 5:16

Which is bad.

SPEAKER_00 5:16

It's universally recognized as one of the primary hallmarks of aging. Your cells literally suffocate because they just can't

Sirtuins And DNA Repair Fuel

SPEAKER_00 5:24

process energy.

SPEAKER_01 5:25

Dude, that's wild. And it doesn't stop with just the mitochondria shutting down because when we talk about NAD plus area, we also have to talk about the sirtuins.

SPEAKER_00 5:33

Ah, yes, the sirtuins.

SPEAKER_01 5:35

Which, going back to the smart home thing, those would be the security guards running the house, right?

SPEAKER_00 5:40

The sirtuins are fascinating. In humans, we have seven of them, Sert T1 through CirceRT7. In the longevity community, you'll hear them constantly referred to as the longevity proteins.

SPEAKER_01 5:50

Right.

SPEAKER_00 5:51

Biochemically, they are NAD plus independent diabetylysis.

SPEAKER_01 5:56

Okay, stop right there. Diacylase explain what that actually means in plain English, because that gets thrown around a lot in these longevity blogs, and it sounds super intimidating.

SPEAKER_00 6:05

Let's break the word down. A deacetylase is an enzyme that removes a specific chemical tag called an acetyl group from other proteins. Think of an acetyl group as a physical clamp on a piece of machinery. When the clamp is on, the machine behaves one way, or maybe it's turned off completely.

SPEAKER_01 6:21

So the sirtuin comes along, rips the clamp off, and suddenly the machine changes behavior, like flipping a molecular switch.

SPEAKER_00 6:28

Yes, that is the exact mechanism. And through this deacetylase activity, sirtuans manage immense cellular responsibilities. They regulate cellular stress responses, they initiate DNA repair when you're exposed to radiation or toxins.

SPEAKER_01 6:44

Wow.

SPEAKER_00 6:45

And they control mitochondrial biogenesis.

SPEAKER_01 6:47

Which means building new mitochondria.

SPEAKER_00 6:49

Exactly. It's the cell's ability to build brand new mitochondria when the old ones wear out.

SPEAKER_01 6:54

That's incredible. So they're just constantly patrolling the cell, flipping switches, telling the body, hey, clean up this misfolded protein, fix that broken strand of DNA, build more engines.

SPEAKER_00 7:03

They are the master regulators. For example, look at Sort3. Sort 3 is localized specifically inside the mitochondria. Its job is to regulate key metabolic enzymes like IDH2 and LCAD.

SPEAKER_01 7:14

And what do those do?

SPEAKER_00 7:15

Well, IDH2 is an enzyme that protects the cell against severe oxidative stress. It neutralizes the toxic byproducts of energy production.

SPEAKER_01 7:24

Sort of like cleaning up the exhaust fumes.

SPEAKER_00 7:26

Exactly. And LCAD stands for long-chain acylcoa dehydrogenase. It's the enzyme that allows your body to break down stored fat for energy instead of just relying on sugar.

SPEAKER_01 7:35

Oh wow. So Certi3 is basically the boss that turns on the fat-burning furnace and the antioxidant defense shield.

SPEAKER_00 7:41

Yes. But here is the critical, non-negotiable catch in all of this biology. Sertuans are strictly dependent on NAD plus Shay.

SPEAKER_01 7:51

Right. The NAD plus a dependent part of the name. If there's no electricity in the smart home, the security guards can't do their jobs. They don't have the fuel.

SPEAKER_00 7:59

They are physically incapable of functioning without it. When sirtuans remove that acetyl plant we talked about, they actually consume a molecule of NAD plus in the process.

SPEAKER_01 8:09

Oh, they use it up?

SPEAKER_00 8:10

Yes. If NAD plus levels drop below a certain threshold, the sirtuins just go dormant. The DNA damage accumulates, the mitochondria

Why “Sirtfoods” Fail In Humans

SPEAKER_00 8:18

don't get rebuilt, and you age.

SPEAKER_01 8:20

Okay. That makes perfect terrifying sense. But wait, since we're talking about fueling sirtuins, uh, I have to ask about this. Because maybe four or five years ago, the internet completely lost its mind over cert foods.

SPEAKER_00 8:30

The certfood diet, I knew we would end up here.

SPEAKER_01 8:33

Dude, people were obsessed. I mean, the entire pitch was that certain foods contain natural compounds that basically force these sirtuan pathways to activate.

SPEAKER_00 8:40

Yes, I remember.

SPEAKER_01 8:41

We're talking drinking green tea for the catechins, eating bowls of berries for anthocyanins, red onions, turmeric for curcumin, and the big one, drinking red wine and eating dark chocolate for the resveratrol.

SPEAKER_00 8:53

The dream diet.

SPEAKER_01 8:54

Literally, people genuinely believe they could drink their way to genetic longevity.

SPEAKER_00 8:59

It is a brilliant marketing pitch because it tells people exactly what they want to hear. Drink wine, eat chocolate, live forever.

SPEAKER_01 9:06

Yeah.

SPEAKER_00 9:07

Unfortunately, the clinical reality is significantly more sobering.

SPEAKER_01 9:12

Come on, ruin the red wine dream for me. Why doesn't it work?

SPEAKER_00 9:15

Well, the premise isn't entirely fabricated. It is based on isolated biochemistry. Many of these plant-derived bioactive molecules, which fall under the general category of polyphenols, they do show an ability to interact with and influence sertuan activity.

SPEAKER_01 9:30

Okay, so it's not a total lie.

SPEAKER_00 9:32

No, but almost all of that foundational evidence comes from preclinical studies.

SPEAKER_01 9:36

Meaning in vitro, like isolated cells floating in a petri dish.

SPEAKER_00 9:40

Exactly. Or, at best, genetically identical mice living in highly sterile cages. The problem happens when you try to translate a chemical reaction in a glass dish to the digestive system of a living human being eating a salad. You run straight into the brick walls of dose, matrix, and bioavailability.

SPEAKER_01 10:00

Okay, explain bioavailability in this context, because I assume when I eat a blueberry, my body is absorbing the nutrients, right?

SPEAKER_00 10:06

Aaron Powell It absorbs some, yes. But polyphenols like resveratrol are heavily subjected to what we call first pass metabolism. What's that? When you swallow it, it goes straight to your liver. And your liver's primary job is to look at foreign chemical compounds, break them down, and excrete them.

SPEAKER_01 10:21

Oh.

SPEAKER_00 10:22

So the bioavailability, the actual amount of intact resveratrol that makes it past the liver and into your bloodstream to reach your cells is fractions of a percent.

SPEAKER_01 10:30

Oh wow. So the liver basically just views it as biological waste and filters it out.

SPEAKER_00 10:35

Mostly, yes. The amount of resveratrol you would need to consume to actually alter your Sirtuan pathways in a meaningful way, is staggeringly high. You couldn't physically drink enough red wine to reach that therapeutic dose without dying of acute alcohol poisoning first.

SPEAKER_01 10:51

Which would, ironically, be very bad for your longevity.

SPEAKER_00 10:54

It would, very bad. And we also have the matrix effect.

SPEAKER_01 10:58

The matrix effect, like living in a simulation.

SPEAKER_00 11:01

Not quite. In a petri dish, you are applying pure isolated curcumin directly to a cell. In human life, you are eating turmeric mixed with fats, fibers, and stomach acid. All of those things physically alter how the chemical is absorbed.

SPEAKER_01 11:16

That makes sense.

SPEAKER_00 11:17

So while these are undeniably healthy foods with general antioxidant properties, the idea that adding capers and green tea to your diet is going to biologically hyperactivate your sertuan genes is just not supported

Why NAD+ Declines With Age

SPEAKER_00 11:28

by clinical reality.

SPEAKER_01 11:29

Okay, so salads and wine aren't the magic fix. Which brings us back to the core mechanical problem. The NAD plus decline itself. If NAD plus is so universally important, if it literally keeps the mitochondrial lights on and the security system running, why do we run out of it? Like, does the human body just get tired of manufacturing it, or is something actively destroying it?

SPEAKER_00 11:50

That has been the central investigative question in aging research for decades. We know empirically that NAD plus levels drop severely with age. The data we are looking at from human tissue samples shows a roughly 50% drop by middle age.

SPEAKER_01 12:04

50%? That's massive.

SPEAKER_00 12:06

It's a huge loss. And for a very long time, the scientific community blamed that decline on enzymes like PRP1 and SRT1.

SPEAKER_01 12:13

Wait, PRP1, that's the enzyme that repairs DNA damage, right?

SPEAKER_00 12:16

Yes. PRP1 is a major consumer of NAD plus cell auto. So the prevailing theory was beautifully simple. As we get older, we are exposed to more UV radiation, more toxins, and we accumulate more cellular damage. Right. Therefore, PRP1 has to work overtime to fix all that broken DNA. And because it consumes NAD plus to do its job, it just aggressively burns through our entire molecular fuel supply.

SPEAKER_01 12:38

Honestly, that sounds completely logical. You get older, you sustain more damage, the repair crew uses up all the supplies. So uh why are you saying prevailing theory in the past tense?

SPEAKER_00 12:49

Because it turned out to be wrong.

SPEAKER_01 12:51

Really?

SPEAKER_00 12:51

Yes. When researchers finally developed the tools to accurately measure the actual protein levels of PARIP1 and SERAT1 in aging mammalian tissues, looking at the liver, white adipose tissue, the spleen, skeletal muscle, they found the exact opposite of what everyone expected.

SPEAKER_01 13:07

Hang on, you're telling me the entire longevity field pointed at PRP1 and said, that's the guy draining the tank, but they didn't actually check the real levels in aging bodies. How does an entire scientific community get that backward?

SPEAKER_00 13:20

It's a great question, and it comes down to methodology. Early studies often measured enzyme activity during states of acute stress.

SPEAKER_01 13:26

Okay.

SPEAKER_00 13:27

If you blast a cell with radiation, PRP1 activity skyrockets. Scientists extrapolated from those acute damage states to assume that chronic aging worked the same way.

SPEAKER_01 13:36

Ah, I see.

SPEAKER_00 13:37

But when they measured resting baseline protein levels across a natural lifespan, they found that PRP1 and RCPA1 levels actually decrease during chronological aging.

SPEAKER_01 13:48

Wait, so the things we thought were eating all the NAD plus are actually disappearing from the cell too?

SPEAKER_00 13:52

Exactly. They are fading away right alongside the NAD plus fiddle number. And while it shocked researchers at first, it actually aligns perfectly with a much older evolutionary concept called the disposable soma theory.

SPEAKER_01 14:05

Okay, what is the disposable soma theory?

SPEAKER_00 14:08

It's a theory proposed in the late 1970s. It suggests that organisms have a strictly limited energy budget. Evolutionarily speaking, a species only needs an individual to survive long enough to reach sexual maturity, reproduce, and maybe rear the next generation.

SPEAKER_01 14:23

Right. Get your genes into the next pool.

SPEAKER_00 14:25

Yes. So it is biologically advantageous to invest your limited cellular energy into immediate growth and reproduction, rather than investing massive amounts of energy into permanently maintaining and repairing the physical body, the soma indefinitely.

SPEAKER_01 14:38

So the body basically says, look, you reproduced, you passed on your genes, my job here is done. I'm not wasting any more energy keeping your DNA pristine.

SPEAKER_00 14:46

Essentially, yes. Evolution has no incentive to keep you vibrant at 80 years old.

SPEAKER_01 14:51

Man, that is just brutally coldly efficient and kind of depressing, honestly. But if parap1 is fading away and the repair crew is packing up and going home, it means they aren't the ones draining the NAD plus Soka. Correct. Which means there's a missing culprit.

SPEAKER_00 15:06

Precisely. Scientists realized they were hunting the wrong suspect. If Parap1 isn't draining the reservoir, what is? And that brings us to the actual undeniable villain of our cellular biology

CD38 Emerges As The Culprit

SPEAKER_00 15:18

story.

SPEAKER_01 15:18

Okay, let's hear it.

SPEAKER_00 15:19

An enzyme called CD38.

SPEAKER_01 15:20

CD38, it sounds like a tax form or some bureaucratic filing curve. What does it do?

SPEAKER_00 15:25

It is what we call an Nidase, meaning its primary biological function is to locate, bind to, and literally chew up NAD plus molecules.

SPEAKER_01 15:33

Oh wow.

SPEAKER_00 15:34

And unlike PRP1, which fades as we age, the expression in the activity of CD38 increase aggressively over time. The studies show that in all tissues tested, CD38 levels increased by two to three times during chronological aging.

SPEAKER_01 15:50

So wait, the body actively ramps up the production of the very thing, destroying its own energy supply.

SPEAKER_00 15:55

Yes. If you look at tissue stains of an aging liver, both the total number of CD38 positive cells and the intensity of the CD38 expression within those cells shoot up dramatically.

SPEAKER_01 16:05

That is wild. It's like a metabolic game of Pac-Man. But as you get older, the game glitches, and suddenly there are three times as many Pac-Men on the board, and they're just aggressively hunting down and eating all your energy pellets.

SPEAKER_00 16:16

That is a phenomenal visualization, truly. And the data supports it perfectly. When researchers plotted the rising curve of C D38 activity against the falling curve of NAD plus levels in aging tissues, the inverse correlation was nearly flawless. As the Pac-Man multiplies, the NAD plus drops.

SPEAKER_01 16:32

But hold on, correlation isn't causation, right? How did they prove this wasn't just two things happening at the same time? Like maybe we just get gray hair and more CD38, but one doesn't cause the other. How did they prove CD38 is actually the one pulling the trigger?

Knockout Mice Prove Causation

SPEAKER_00 16:48

They proved it through genetic manipulation. It's detailed in a really fascinating study published in the journal Cell Metabolism. They use water called CD38 knockout mice.

SPEAKER_01 16:58

Knockout mice! Meaning they went into their DNA and literally deleted the gene that creates CD38.

SPEAKER_00 17:04

Exactly. They engineered a lineage of mice to completely lack the CD38 enzyme. So we have our wild type mice.

SPEAKER_01 17:11

Which is the normal mice, right?

SPEAKER_00 17:12

Right. The normal unmutated mice you'd find in nature. And we have our CD38 knockouts. The researchers just let them age normally and watch what happened to their cellular batteries.

SPEAKER_01 17:21

Did the knockouts turn into super mice?

SPEAKER_00 17:23

Biochemically, you could definitely call them that. The results were striking. The knockout mice maintained youthful, high capacity NAD plus levels, even when they were chronologically old.

SPEAKER_01 17:35

No way.

SPEAKER_00 17:36

Their NAD plus reservoir simply didn't crash because the Pac-Man wasn't there to eat it.

SPEAKER_01 17:40

Whoa. So just by deleting that one enzyme, the battery stays green.

SPEAKER_00 17:45

Yes. And because their NAD plus stayed high, their downstream cellular machinery remained totally intact. The researchers specifically measured the activity of the mitochondrial complexes, complex one, three, and four.

SPEAKER_01 17:58

Which are the physical stations on that ATP assembly line we talked about earlier?

SPEAKER_00 18:02

Correct. In normal old mice, those complexes degrade. In the knockout mice, their function was perfectly preserved. They demonstrated higher oxygen consumption, and their SRT3 activity, that mitochondrial security guard, stayed highly functional.

SPEAKER_01 18:17

Okay, that is incredibly compelling. But did they test it in reverse? Like if you take a young, healthy cell and force it to make too much CD38, does it instantly age?

SPEAKER_00 18:25

They did exactly that. They took normal, healthy human cells, kidney cells in this specific experiment, and they genetically forced them to overexpress CD38 to just flood the intracellular environment with the NIDAS.

SPEAKER_01 18:36

Let me guess. Complete metabolic collapse.

SPEAKER_00 18:39

Total dysfunction. By artificially ramping up CD38, they induced severe NAD plus loss, which, as we now know, immediately suffocated the mitochondria. The respiration rate plummeted, and the fill showed a massive increase in lactate release.

SPEAKER_01 18:53

Why lactate like lactic acid from working out?

SPEAKER_00 18:56

Exactly the same thing. When mitochondria fail and can no longer process oxygen for energy, the well panics. It falls back on a primitive, highly inefficient backup system called fermentation to survive. A byproduct of cellular fermentation is lactate. So a spike in lactate is a massive flashing warning light that the mitochondria are suffocating. The CD38 literally choked out the cell's energy supply by degrading all the NAD plus and NADH.

SPEAKER_01 19:24

Okay, so CD38 is definitively the saboteur. We've

Why NAD+ Pills Cannot Work

SPEAKER_01 19:28

solved the mystery of why the battery is blinking red. So I mean, logically, if we know CD38 is the thing eating our NAD plus Dell, the obvious next step is figuring out how to outpace the destruction.

SPEAKER_00 19:38

That's where most people's minds go, yes.

SPEAKER_01 19:40

Can we just swallow more NAD plus steps? Because I've seen bottles of straight NAD plus online. Can we just take a pill and flood the system faster than the Pac-Man can eat it?

SPEAKER_00 19:48

You would think it would be that simple, but unfortunately, it is physically impossible. You cannot just take NAD plus pills to raise intracellular levels.

SPEAKER_01 19:57

Why not? If it's the exact molecule the body needs.

SPEAKER_00 20:00

Because of the physical structure of the molecule itself. NAD Plus is a very large, bulky molecule, and crucially, it carries a heavy electrical charge.

SPEAKER_01 20:10

Okay, and why does that matter?

SPEAKER_00 20:11

The membrane that surrounds every cell in your body is specifically designed to repel large, charged molecules to protect the interior. If you put pure NAD plus into your bloodstream, it just bounces right off the cellular walls. It cannot enter the cell where it's actually needed.

SPEAKER_01 20:28

Oh, so it's like trying to shove a completely assembled Ferrari through the front door of your house instead of just bringing in the parts and building the car in the living room.

SPEAKER_00 20:36

Exactly. The cell membrane is a locked door for the fully assembled car. And those individual car parts are what biologists call precursors. If you want to raise the NAD plus levels inside the mitochondria, you have to feed the cell the smaller, uncharged raw materials that it can easily absorb, pull inside, and then assemble into NAD plus MELLER.

SPEAKER_01 20:57

Okay, and this brings us to the massive billion-dollar supplement industry, the precursors. You

NR Versus NMN And Bottlenecks

SPEAKER_01 21:02

hear two acronyms constantly, NMN and NR.

SPEAKER_00 21:06

Yes. Nicotinamide mononucleotide, which is NMN, and nicotinamide riboside, which is NR. Both of these molecules exist to utilize what we call the NAD plus salvage pathway.

SPEAKER_01 21:17

The salvage pathway, like a molecular recycling center.

SPEAKER_00 21:20

That's exactly what it is. Biology is highly efficient. Normally, when enzymes like certumans use a molecule of NAD plus to repair some DNA, they don't destroy it completely. They break off a piece, leaving behind a byproduct called NAM or nicotinamide. The salvage pathway takes that leftover NAM and painstakingly recycles it back into fresh NAD plus mellar.

SPEAKER_01 21:39

So why do we need supplements if we have a built-in recycling center?

SPEAKER_00 21:42

Aaron Ross Powell Because the recycling center has a bottleneck. The conversion relies on a very specific enzyme called NAPT. That is the rate limiting step in the salvage pathway.

SPEAKER_01 21:51

Rate limiting meaning uh like rush hour traffic all trying to merge into a single lane. It can only go so fast no matter how many cars are waiting.

SPEAKER_00 21:59

Correct. Now a very common question people ask is why spend a hundred dollars on fancy NMN supplements when I can go to the pharmacy and buy a giant bottle of basic vitamin B3 niacin for five dollars. Niacin is an NAD plus precursor too.

SPEAKER_01 22:15

Right. I've seen longevity guys talk about basic niacin. Does that work?

SPEAKER_00 22:19

It does raise NAD plus NA, but it comes with severe biological penalties. Taking high doses of nicotinic acid basic niacin triggers a massive release of prostaglandins in the body.

SPEAKER_01 22:30

And what does that do?

SPEAKER_00 22:31

This causes intense dilation of the blood vessels, resulting in severe full body skin flushing. It feels like a horrible sunburn from the inside out, and it's incredibly uncomfortable.

SPEAKER_01 22:41

Okay. Nobody wants a permanent internal sunburn. What if we just take pure NAM, the recycled byproduct you mentioned?

SPEAKER_00 22:47

If you try to flood the system with too much NAM, it runs straight into that NAMPT traffic jam we mentioned. It can't process it fast enough.

SPEAKER_01 22:54

So it just backs up.

SPEAKER_00 22:55

Worse than that, if massive amounts of NAM pool up inside the cell waiting to be recycled, it actually causes feedback inhibition. The excess NAM literally binds to the sertuans and turns them off, which is the exact opposite of the longevity effect you're trying to achieve.

SPEAKER_01 23:13

Oh wow. So cheaping out on basic B vitamins could actually accelerate aging by shutting down the security guards. That is terrifying. Okay, so basic vitamins are out. What makes NR and NMN so mathematically special?

SPEAKER_00 23:25

They are molecularly designed to bypass those exact bottlenecks. They essentially jump the line. NR is highly praised in the literature because it's a very small molecule, meaning it easily slips right through the cell membrane without needing a special door.

SPEAKER_01 23:38

Okay, what about NMN?

SPEAKER_00 23:39

NMN is slightly larger, but recent groundbreaking research discovered that our bodies have evolved specific transporters, a protein called SLC12A8, found heavily in the gut, that act as dedicated turnstiles, actively pulling NMN directly into the cells.

SPEAKER_01 23:53

So they slip past the cell walls, bypass the traffic jam, and immediately assemble into NAD plus C. We did it. We figured out the puzzle. Just take NMN, build the battery fluid, and outpace the C D38 Pac-Man.

SPEAKER_00 24:06

If only human biology

CD38 Eats Precursors In Blood

SPEAKER_00 24:08

were that cooperative. Yeah. This is where the literature drops a massive frustrating bombshell. You remember our saboteur?

SPEAKER_01 24:14

CD38, the Pac-Man.

SPEAKER_00 24:16

Well, what researchers found is that CD38 doesn't just destroy fully assembled NAD plus and B, it is also the primary enzyme in the mammalian body that degrades NMN in vivo.

SPEAKER_01 24:27

Wait, what? Are you serious?

SPEAKER_00 24:28

Completely serious. In vivo just means inside the living organism rather than in a test tube. CD38 acts as what we call an ectoenzyme.

SPEAKER_01 24:36

Meaning what?

SPEAKER_00 24:37

It means that while the enzyme is anchored in the cell membrane, a large portion of its catalytic destructive machinery actually faces outward into the extracellular space.

SPEAKER_01 24:45

Into the bloodstream.

SPEAKER_00 24:46

In your bloodstream. Oh no. Yes. When you swallow an expensive NMN supplement and it enters your bloodstream, it doesn't just neatly float to the cells that need it. The outward-facing CD38 enzymes recognize the NMN in the blood and actively chew it up before it can even cross the membrane to do its job.

SPEAKER_01 25:05

That is genuinely devastating. So you're spending all this money on these cutting-edge supplements, and your body is literally using its own aging enzymes to intercept and eat the medicine before it even reaches the cellular living room.

SPEAKER_00 25:17

In a very large part, yes. They tested this dynamic directly. They took wild type mice and gave them an intravenous injection of NR. Then they measured the blood. The levels of NR dropped violently, a 25% decrease in just the first 75 minutes.

SPEAKER_01 25:31

Because the CD38 was immediately ripping it apart in the blood.

SPEAKER_00 25:34

Exactly. But then they took the C D38 knockout mice, the ones without the Pac-Man enzyme, and gave them the exact same injection. In those mice, the circulating levels of NR and MN and fully formed NAD plus stayed significantly more stable. Wow. Even two and a half hours later, the knockout mice had vastly higher levels of the precursor circulating their plasma.

SPEAKER_01 25:55

So the Pac-Man isn't just eating the power pellets inside the cell, it has its mouth hanging outside the cell, eating the delivery trucks bringing the new power pellets?

SPEAKER_00 26:03

That is a perfect way to conceptualize an ectoenzyme.

SPEAKER_01 26:06

Wait, hold on. I'm looking at a logical gap here. If CD38 is sitting in the bloodstream chewing up all the NMN, how do all these human clinical trials claim that taking NMN raises blood NAD plus levels? If the delivery trucks are getting destroyed, how is the cargo getting delivered?

SPEAKER_00 26:24

That is a very askewed question. It comes down to two factors: saturation and tissue distribution. When you take a massive clinical dose, say a thousand milligrams of NMN, you're throwing so many delivery trucks at the system that you temporarily saturate the CD38 enzymes.

SPEAKER_01 26:40

Oh, they just can't eat it fast enough.

SPEAKER_00 26:41

Exactly. They are eating as fast as they can, but a certain percentage of the NMN simply slips past the bottleneck and makes it into the cells. Furthermore, certain tissues, particularly the liver, are incredibly efficient at absorbing these precursors the second they enter circulation, converting them into NAD plus D and then releasing them back into the blood in different forms.

SPEAKER_01 27:01

Okay, so it's a brute force attack. You just overwhelm the Pac-Man with sheer volume.

SPEAKER_00 27:05

Precisely. But it brings us to the most crucial part of this entire deep dive. We've talked extensively about mice. Mice living in sterile environments get longer lifespans, better muscles, and preserve mitochondria from these precursors.

SPEAKER_01 27:18

Right.

SPEAKER_00 27:18

But what actually happens when complex human beings take them? Because I know regular people right now taking a thousand milligrams of NMN every single morning.

What Human Trials Show

SPEAKER_00 27:28

I need to know if the expensive powder sitting in their medicine cabinets is actually reversing their biological age, or if they just have really, really expensive NMN-rich urine.

SPEAKER_01 27:37

This is where we make the critical transition from the preclinical hype to the harsh clinical reality, right? Let's look at the human clinical trials, specifically focusing on the comprehensive reviews compiled in 2025 and 2026.

SPEAKER_00 27:49

The reality check.

SPEAKER_01 27:50

Bring it on. I need the truth. Start with the good news, if there is any.

SPEAKER_00 27:54

There is definitively good news. The trials unequivocally prove that oral precursors, specifically NR, at doses of around 1000 milligrams a day, and NMN at similar doses, are safe for human consumption.

SPEAKER_01 28:07

Okay, so it won't hurt you acutely.

SPEAKER_00 28:09

Right. They do not cause acute toxicity. And as we just discussed, they do successfully and reliably raise NAD plus levels in human whole blood.

SPEAKER_01 28:18

So the brute force method works, the blood battery gets charged.

SPEAKER_00 28:22

Yes, and we see significant NAD plus increases specifically in PBMCs.

SPEAKER_01 28:26

Which are what?

SPEAKER_00 28:27

Peripheral blood mononuclear cells. They are a critical component of your immune system, things like T cells and B cells circulating in your blood. Elevating NAD plus in those cells could theoretically help maintain immune function as we age.

SPEAKER_01 28:40

That's definitely a plus.

SPEAKER_00 28:41

But beyond just blood markers, there are some very promising specific clinical applications emerging. For example, a landmark 2026 study focused on patients with Parkinson's disease.

SPEAKER_01 28:51

Oh, neurodegeneration. That's a huge target for anti-aging.

SPEAKER_00 28:55

Massive. In this trial, they gave Parkinson's patients a high daily dose of NR using magnetic resonance spectroscopy, which is a specialized MRI technique that uses powerful magnets to actually measure the chemical bonds of specific metabolites inside living tissue. They proved that the oral NR actually increased cerebral NED plus levels.

SPEAKER_01 29:14

Whoa. Wait, it crossed the blood-brain barrier. That is notoriously difficult to do. Most drugs just bounce right off the brain's defense system.

SPEAKER_00 29:22

It is a phenomenal finding. Showing that an oral supplement can alter the neurochemical environment of the human brain opens up massive therapeutic potential for diseases like Parkinson's and Alzheimer's.

SPEAKER_01 29:34

That is legitimately incredible.

SPEAKER_00 29:36

Additionally, in broader populations, we see some trials showing mild but statistically significant improvements in muscle endurance in older adults. We also see some slight cardiometabolic improvements, like reduced arterial stiffness and more favorable lipid profiles in certain demographics.

SPEAKER_01 29:54

Okay, so it's not totally fake. It is doing something tangible in the human body. But uh you use the words mild and slight. You're an analytical person. I sense a massive butt hovering over this data.

SPEAKER_00 30:04

A very large butt. While the blood levels of NAD plus reliably go up across the board, the human trials consistently reveal something deeply baffling to the researchers. When they take physical biopsies of the patient's skeletal muscle, the NAD

Muscle NAD+ Stays Flat

SPEAKER_00 30:18

plus steady state levels remain completely unchanged.

SPEAKER_01 30:21

Wait, what? Unchanged? But you just said they recorded mild improvements in muscle endurance. How on earth is the endurance improving if the battery inside the muscle tissue isn't actually charging?

SPEAKER_00 30:32

That is the grand mystery currently confounding the field. It's not that the supplement isn't reaching the muscle tissue. We know for a fact it is getting there.

SPEAKER_01 30:41

How do we know that if the levels don't go up?

SPEAKER_00 30:44

Because when researchers analyze those muscle biopsies, they see massive spikes in the metabolites of NAD plus breakdown. When NAD plus is used and discarded by the cell, it creates clearance products, specifically things like MenAM, which stands for methylated nicotinamide. The muscle biopsies are absolutely flooded with MenAM.

SPEAKER_01 31:03

Let me make sure I'm wrapping my head around this. So the engine is running, the exhaust pipe is blowing out massive clouds of smoke, meaning all those breakdown metabolites. But when you check the gas tank, the actual NAD plus level looks exactly the same.

SPEAKER_00 31:14

That is a brilliant analogy. Yes. It suggests there is a massive metabolic flux occurring. The muscle tissue is rapidly pulling in the precursors, aggressively building NAD plus ray, and then instantly burning it up to power the cell, but it never allows the baseline, steady state reservoir to actually rise. Wow. And this highlights a fundamental, inescapable difference between laboratory mice and human beings. Humans are not simply giant mice.

SPEAKER_01 31:40

I mean, I would hope not, but biochemically, what's the difference here?

SPEAKER_00 31:43

It comes down to the basal metabolic rate. A mouse lives incredibly fast and dies very young. Their baseline cellular metabolism is roaring constantly. So when you flood a mouse with NAD plus precursors, their rapid metabolism immediately incorporates it, yielding these massive, highly visible physiological rejuvenations.

SPEAKER_01 32:01

Oh, I see.

SPEAKER_00 32:01

In humans, our evolutionary strategy is a slow burn. Our metabolic rate is significantly lower. This slower biology dictates a very different, much more conservative response to how NAD plus deficits are generated and how they were repaired. The human body is highly resistant to rapid cellular reprogramming.

SPEAKER_01 32:18

Okay, that actually makes total sense. A mouse is like a Formula One sports car constantly redlining, so if you inject premium fuel into the system, the engine screams to life immediately. Humans are more like a massive diesel freight train just idling along. You pour in premium fuel and the train just keeps idling exactly the same way.

SPEAKER_00 32:36

Well said. But the slower metabolism isn't even the most complex hurdle. There's another uniquely human complication that researchers recently uncovered, and it completely rewrites how we view these oral supplements. We have to talk about the microbiome.

SPEAKER_01 32:51

The gut bacteria.

Metabolism Differences Between Species

SPEAKER_01 32:52

What do the microbes in my stomach have to do with my cellular DNA repair?

SPEAKER_00 32:56

Everything, it turns out. During these human trials, researchers noticed a very strange anomaly in the blood work. When human participants swallow oral NR capsules, their blood work suddenly shows a massive, unexpected spike in a specific molecule called NAD.

SPEAKER_01 33:12

NAAD, what is that?

SPEAKER_00 33:14

NAD is a chemical intermediate, is a part of the priesthandler pathway. And if you recall from our earlier biochemistry discussion, the priest handler pathway is the specific metabolic route the body uses to process nicotinic acid, which is basic, cheap, flush-inducing niacin.

SPEAKER_01 33:31

But wait, you explicitly said earlier that NR uses the salvage pathway to bypass the bottleneck. It doesn't use the price handler pathway. Why would a niacin marker be spiking in the blood if they are taking NR?

SPEAKER_00 33:43

Exactly. It made absolutely zero biochemical sense until researchers zoomed out and look at what was happening in the human digestive tract before the supplement even reached the bloodstream. When you swallow a capsule of NR, it drops into your gut. And your gut microbiome, the trillions of bacteria living in your intestines, intercepts a huge portion of it.

SPEAKER_01 34:01

Wait, the bacteria eat the supplement.

SPEAKER_00 34:03

Yes. Specific strains of gut microbiota express an enzyme called nicotinidase. When the highly advanced, expensive NR molecule floats by, the bacteria snatch it up and use that enzyme to physically cleave the riboside group right off the molecule. They strip it down. And what's left over after they strip it? Nicotinic acid, basic niacin.

SPEAKER_01 34:25

You've got to be kidding me.

SPEAKER_00 34:26

I am not. The bacteria covert it to niacin. Then your intestinal wall absorbs that bacteria created niacin, which forces your liver to process it through the price handler pathway, generating all that NAAD we see in the blood tests.

SPEAKER_01 34:39

So let me get this straight. You go online, you pay absolute top dollar for chemically advanced, highly stabilized nicotinamide ribocytes specifically designed to bypass the cellular bottlenecks. And your own gut bacteria just mug the supplement in your stomach, strip it down, and turn it back into the cheap $5 pharmacy niacin before your body even gets a chance to use it.

SPEAKER_00 34:56

In a significant number of cases, yes, it completely reshapes our understanding of how oral precursors actually work in a living human. It's a prime example of why human biology is so much more stubbornly complex than isolated cell cultures in a lab.

SPEAKER_01 35:11

Okay, this is genuinely blowing my mind. So if we review the facts, the clinical results in humans are mostly mild. The muscle battery levels don't really rise at all. The CD38 Pac-Man is eating the supplement in the blood, and our gut bacteria are intercepting the payload in the stomach.

SPEAKER_00 35:27

Aaron Powell Yes. That is an accurate summary.

SPEAKER_01 35:29

Aaron Powell Why is the hype so deafening? Why is everyone from tech billionaires to fitness influencers pushing NMN and NR as a miracle fountain youth cure? Why is there a billion-dollar industry built on this right now?

SPEAKER_00 35:40

Aaron Powell We have to have a very frank

Microbiome Hijacks NR Into Niacin

SPEAKER_00 35:42

conversation about the hype problem in modern science. The anti-aging industry has historically always been susceptible to hyperbolic claims, but NAD plus boosters are currently the absolute epicenter of the storm. The commercialization of NR and NMN has been vastly artificially amplified by a combination of celebrity endorsements and highly prominent vocal researchers.

SPEAKER_01 36:02

Yeah, I mean, you can't talk about NMN without talking about those huge celebrity scientists from places like Harvard, right? They're on every major talk show, writing books, constantly talking about this stuff.

SPEAKER_00 36:14

Aaron Powell Yes, their advocacy, along with others, has brought massive mainstream visibility to molecules like NMN. And while the foundational biology they study is real, we absolutely must look at the structural conflicts of interest driving the narrative. Many of the human clinical trials validating these supplements are heavily industry funded. Shocking. For example, companies like Chromodex are massive funders of NR research, and they are simultaneously one of the largest patent holders and commercial sellers of NR supplements in the world.

SPEAKER_01 36:44

That feels like a massive red flag. We investigated our own product and found it to be amazing.

SPEAKER_00 36:49

To be fair to the scientific process, industry funding does not automatically invalidate a study's raw data. The blood levels really do go up. But the conflict of interest dictates how that data is framed. They are highly motivated to highlight surrogate markers, shouting, look, blood NAD plus increase by 40%, rather than acknowledging the lack of hard clinical endpoints.

SPEAKER_01 37:13

Explain the difference between a surrogate marker and a clinical endpoint.

SPEAKER_00 37:17

A surrogate marker is a biological number on a piece of paper. Blood pressure, cholesterol levels, or in this case NAD plus concentration in the blood. A clinical endpoint is an actual physical health outcome. Did the patient live longer? Did they avoid a heart attack? Did their biological aging actually slow down? Right. The industry markets the surrogate marker as if it is a guaranteed clinical endpoint.

SPEAKER_01 37:38

Right. We changed a number on your blood test, is biologically very different from we just made your organs genetically 10 years younger.

SPEAKER_00 37:45

Exactly. And the direct consumer marketing machine completely blurs that line for the average buyer. But honestly, the marketing spin isn't even the most concerning part of the industry right now. It's the catastrophic lack of quality control and the hidden theoretical risks that nobody wants to talk about.

SPEAKER_01 38:02

Aaron Powell Quality control. Like are people just straight up not getting what they pay for?

SPEAKER_00 38:06

Far from it.

SPEAKER_01 38:06

Okay.

SPEAKER_00 38:07

Because NMN and NR are legally classified and sold as dietary supplements, they are not regulated by the FDA like pharmaceutical drugs. Independent laboratory analyses of the commercial market have found massive widespread purity issues. Some of the most popular commercial NMN supplements on Amazon contain 30 to 70 percent less active ingredient than what is legally claimed on the label.

SPEAKER_01 38:28

So it's basically expensive flour.

SPEAKER_00 38:30

Or worse. Some independent tests found batches heavily contaminated with basic unrefined nicotinamide, the NAM we discussed earlier.

SPEAKER_01 38:38

Oh no.

SPEAKER_00 38:39

And as we established, if you take massive unregulated doses of raw NAM, it actually causes feedback inhibition, shutting down your Sertuan longevity genes. You are essentially paying premium prices for highly unpredictable, unregulated chemistry that could be actively working against you.

SPEAKER_01 38:57

That is infuriating. You think you're buying a highly engineered Ferrari part for your cellular engine, and you're actually getting a counterfeit dirty lawnmower spark plug.

SPEAKER_00 39:05

And this brings us to a much darker, much more serious biological reality. A theoretical risk that the longevity

Marketing Hype And Conflicts

SPEAKER_00 39:12

influencers almost universally ignore.

SPEAKER_01 39:14

Okay, I'm braced. What is it?

SPEAKER_00 39:15

We have spent the last half hour talking about how NAD plus is the fundamental non-negotiable fuel for cellular energy and rapid DNA repair, correct?

SPEAKER_01 39:24

Yeah, it's the battery fluid. It fuels everything.

SPEAKER_00 39:26

Well, think about human pathology for a second. What specific type of cell has the highest, most aggressive energy demand in the entire human body? What type of cell is constantly, furiously multiplying, ignoring all biological stop signs, and is utterly desperate for raw metabolic fuel and constant DNA repair mechanisms to survive its own rapid mutation?

SPEAKER_01 39:46

Oh man, oh no, cancer cells.

SPEAKER_00 39:49

Exactly, cancer. Preclinical models have recently illuminated a very concerning dark side to artificial NAD plus augmentation. In highly specific mouse models of lymphoma and certain types of breast cancer, researchers found that providing the mice with NAD plus precursors actually rapidly accelerated tumor progression.

SPEAKER_01 40:09

Because cancer relies on glycolysis and the salvage pathway, right? So if you flood the body with NMN, you aren't just fueling the healthy cells. You're giving the cancer cells the exact premium fuel and repair kits they need to multiply out of control.

SPEAKER_00 40:22

That is the exact mechanism. Cancer cells experience massive amounts of oxidative stress and DNA damage because they divide so recklessly. They desperately rely on PREP enzymes to constantly patch their broken DNA so they don't simply die. And as we know, PRP strictly requires NAD plus to function. Man. By taking massive doses of precursors, you are theoretically ensuring the cancer's repair mechanisms never run out of fuel.

SPEAKER_01 40:45

That is a staggering reality check.

SPEAKER_00 40:48

Now, it is absolutely crucial that I state this clearly. We do not have clinical evidence that taking NR or NMN causes new cancers to form in healthy human beings. It does not seem to be a carcinogen in that way.

SPEAKER_01 41:00

Okay. That's somewhat of a relief.

SPEAKER_00 41:02

But human biology is messy. If a person has an undiagnosed, dormant microtumor, which many aging adults do, or if they have a personal history of cancer and remission, flooding their systemic circulation with highly bioavailable NAD plus precursors could theoretically act as a metabolic accelerant for those dormant cells. It is a profound biological gamble that the bright, optimistic, direct-to-consumer marketing completely ignores.

SPEAKER_01 41:29

Wow, okay. That is that's a lot to process. That completely changes how I view those little white bottles. If I'm taking all this in, let me try to synthesize the big takeaways from this entire deep dive.

SPEAKER_00 41:39

Please do. It's a complex web.

SPEAKER_01 41:40

Okay. On a fundamental level, NAD plus is undeniably our vital cellular fuel. It is the literal electricity for the mitochondria. It's the required fuel that allows the Sertuan security guards to repair our DNA, and

Purity Problems And Cancer Risk

SPEAKER_01 41:52

losing it is a core reason why we biologically age. That part is true.

SPEAKER_00 41:55

Completely true. The foundational biology is solid.

SPEAKER_01 41:58

But as we age, a rogue outward-facing enzyme called CD38 acts like a biological Pac-Man. It aggressively multiplies and just starts eating our NAD plus supply, causing the whole system to choke. And while laboratory scientists have figured out that you can use precursor parts like NR and NMN to bypass the cell walls and theoretically rebuild the battery, the human translation is an absolute mess.

SPEAKER_00 42:22

A messy, unpredictable translation.

SPEAKER_01 42:24

Yes. The CD38 Pac-Man intercepts the supplements in the blood. Our gut bacteria hijack the capsules in our stomachs and downgrade them to cheap niacin. The actual anti-aging results in human muscle tissue are incredibly modest compared to the marketing hype. You're probably buying counterfeit or underdose supplements anyway, and worst of all, if you happen to have a hidden microtumor, you might just be handing it the exact premium peel it needs to kill you.

SPEAKER_00 42:47

You have captured the nuance perfectly. The biochemistry of NAD is undeniably fascinating. And as we saw with the Parkinson's brain data, it holds profound, legitimate therapeutic promise for specific degenerative diseases when administered correctly. But biology is incredibly stubbornly complex. Preserving human health span and delaying mortality is never ever going to be as simple as swallowing a single isolated compound from a plastic bottle you bought on the internet.

SPEAKER_01 43:18

Yeah. It's a sobering reminder for you listening right now. Whenever someone promises you a biological shortcut or tries to sell you immortality for 80 bucks a month, rid the fine print.

SPEAKER_00 43:27

Exactly. You cannot outsmart millions of years of evolutionary biology with a single chemical loophole. And honestly, looking at the totality of this research, it leaves us with a lingering, somewhat provocative question about the entire future direction of the longevity field. What's right now, the entire industry is spending billions of dollars trying to out supplement the aging process. We are desperately trying to flood our bodies with massive, unnatural doses of NAD plus precursors, just hoping that enough molecules slip past the gut bacteria, survive the liver, and eventually. The cellular defenses to make a tiny difference in the tissue.

SPEAKER_01 44:03

Right. We're just blindly throwing thousands of power pellets into the maze, hoping we outpace the Pac-Man by sheer volume.

SPEAKER_00 44:09

Aaron Powell Precisely. But if C D thirty eight is the primary undeniable driver of this age-related decline, if it's the Pac-Man that not only drains our natural endogenous

The Case For CD38 Inhibitors

SPEAKER_00 44:20

NAD plus reservoir, but also actively chews up the expensive NMN supplements we swallow before they even reach the cell, shouldn't the future of anti-aging medicine pivot completely? Instead of trying to endlessly fuel the system, shouldn't we be focused on finding a safe, precise way to simply switch off the Pac-Man?

SPEAKER_01 44:36

Oh wow, yeah. Don't buy more gas, just unplug the C D thirty eight.

SPEAKER_00 44:39

Yeah. Exactly. Instead of constantly trying to refill a biological bucket that has a massive growing hole in it, perhaps the next great leap in human longevity won't be a new highly marketed precursor supplement at all. Perhaps the true breakthrough will be a targeted molecular C D thirty eight inhibitor, something that just patches the hole, turns off the enzyme, and allows our bodies to naturally restore their own youthful energy levels without interference. Just something to critically think about the next time your feed serves you an ad for a miracle longevity pill.