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Aug 2, 2026
The enzyme that eats your NAD
The enzyme that eats your NAD
00:00
07:24
Transcript
0:00
Welcome to The Longevity Expert. I'm Dave, and this is the show where we take one piece of real science about aging well and turn it into something you can actually use.
0:11
No hype, no thirty-step routines, just what the evidence says and what to do about it in about ten minutes. Today, the other half of a story we covered a few months back. We talked about NAD and the case for raising it.
0:26
That case still stands, but it was only half the equation, and the other half explains something that almost never gets discussed.
0:34
Everything I cover on this show comes from The Longevity Expert, my free weekly newsletter. The podcast gives you the science. The newsletter gives you the exact protocol to act on it.
0:46
So let's talk about the half nobody mentions. Almost every conversation about NAD focuses on production. Take a precursor, make more NAD, and that part is well supported. It is worth doing.
1:00
But your NAD level is not a production number. It is a balance, what you make minus what you lose, and the loss side is dominated by a single enzyme. Here is the study that reframed the whole field.
1:14
In twenty sixteen, researchers at the Mayo Clinic published work in cell metabolism looking at what actually happens to NAD as animals age. And what they found was not what anyone expected.
1:27
The enzymes responsible for making NAD did not fall very much. What changed dramatically was an enzyme called CD38. Its levels and its activity climbed across multiple tissues with age.
1:41
By thirty-two months, normal mice had roughly half the NAD of a young mouse. Now here is the part worth sitting with. Mice engineered without CD38 showed no age-related NAD decline at all. None.
1:57
Remove one enzyme, and the decline that defines NAD aging largely does not happen. Then comes the detail that matters most if you take a precursor. CD38 does not only break down NAD, it breaks down NMN.
2:14
So in an older body where CD38 activity is elevated, a portion of the NMN you take is degraded before it can be converted into NAD. Now, be careful how you read that because it is easy to draw the wrong conclusion.
2:29
It does not mean NMN stops working. Human trials consistently show that NMN raises blood NAD, and that finding is solid. Think of a daily precursor as basic housekeeping, foundational, worth doing,
2:45
the thing you keep doing. What it does not do is touch the drain. Fill faster and the level still rises. Narrow the drain as well and the same dose goes further.
2:57
There is a third piece here, and it connects this to almost everything else we cover on this show. CD38 is expressed heavily on senescent cells and on inflammatory immune cells.
3:08
Senescent cells are the ones that stop dividing but refuse to die and keep leaking inflammatory signals into healthy tissue.
3:15
As those accumulate with age, CD38 rises with them, which means chronic inflammation, the thing we covered in the inflammaging episode, is one of the things holding your NAD drain open.
3:28
These are not two separate problems. They are the same problem seen from two angles. Let me explain the mechanism properly because it tells you where the leverage is.
3:38
CD38 sits on cell membranes and consumes NAD as part of immune signaling. In a young body, its activity is modest.
3:48
With age, driven by rising inflammation and accumulating senescent cells, it climbs across the liver, the brain, the heart, muscle, and fat tissue. Every unit of CD38 activity is a unit of NAD consumption.
4:04
And because it also cleaves NMN, some of the precursor you take is broken down by that same enzyme before it can be converted.
4:12
So the practical result is this: NAD decline is a destruction problem as much as a production shortfall. Adding raw material works.
4:20
Adding raw material while also lowering inflammation works better because you are widening the inflow and narrowing the outflow at the same time. So the obvious question, can you close the drain? In animals, yes.
4:34
Blocking CD38 with an experimental compound extended median lifespan in aged mice by about ten percent.
4:43
And a twenty thirteen study found that a plant flavonoid called apigenin inhibits CD38 and raised NAD in mouse tissue. Apigenin is the one you can actually buy. It is found in parsley, celery, and chamomile.
4:58
Now, strength of evidence, 'cause this is where I try to be straight with you every week. The CD38 biology itself is high confidence. The twenty sixteen work is widely replicated.
5:11
CD38 is now broadly accepted as the main NAD-degrading enzyme in mammalian tissue, and it clearly rises with age. The animal data on blocking it is strong, so the mechanism is real and well-characterized.
5:27
The other interventions for protecting your NAD are the unglamorous ones. Exercise, controlling inflammation, sleep, reducing visceral fat. Those come first, and nothing you buy replaces them. One note before I wrap.
5:42
In this week's newsletter, I do include a product recommendation because Solensis has just launched a formula built around exactly this two-sided idea.
5:51
NMN at five hundred milligrams for production plus apigenin at fifty milligrams aimed at the loss side with six other actives around it. It is the one I take alongside my usual powder rather than instead of it.
6:06
Seventy-one ninety-six for readers with a ninety-day guarantee. The link is in the show notes and so is the honest evidence caveat I just gave you. That is the science, and that is where this episode stops.
6:19
Because in the newsletter, I have laid out the practical side, the levers that actually lower CD38 activity with human evidence behind them. How to think about your precursor if you already supplement.
6:33
A drug interaction that genuinely matters if you take prescription medication, plus a thirty-day plan you can follow. The link is in the show notes. One safety note before I go.
6:44
Apigenin inhibits several cytochrome P450 liver enzymes, which your body uses to metabolize a lot of common medications.
6:53
If you take prescription drugs, especially blood thinners or statins, talk to your doctor or pharmacist before adding a concentrated apigenin supplement. That is a real interaction, not boilerplate.
7:06
And if you are new here, the single best thing you can do is subscribe to the newsletter. It is free, it lands every week, and it is where the science becomes something you can actually do. The link is in the show notes.
7:18
Until next week, keep building a body that lasts. This has been The Longevity Expert.
The Longevity Expert
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