DNA repair enzymes like PARP use NAD+ as a substrate, contributing to NAD+ decline with age.

“we don't have enough of the substrate that the ceran needs to repair DNA and that substrate is NAD”

“thankfully our bodies have a system to repair that it's called Park which is an enzyme called poly adp-ribose polymerase and nad is actually a molecule that has two it has one ATP there's an actual molecule of adp within a in any day a lot of people don't know that but it is so what this part benzine does is it sucks out that ATP molecule and it makes these this matrix of ribose polymers that essentially serve as a substrate so the DNA repair enzymes can come in and repair that damage but you they can't work without that substrate or the matrix”

“the DNA breaks from the non ionizing radiation and the carbonyl radicals are causing the PARP enzyme staff to work over time and that's gonna consume nad yeah and the converse of that obviously if you're any D levels are low like you have low muscle mass or you've got this chronic EMF exposure then yeah the particles would consume that if they could but if there's not enough nad they can't and then you have DNA damage and you're you're getting these mutations that are not being repaired”

“when parp goes to make these tails or these flags on the dna it takes nad nicotinamide adenine dinucleotide and the the nicotinamide molecule is cleaved off and you get these adp ribose chains is that right”

“what we found was that by raising the levels of nad the fuel for the enzyme park uh that we could restore the activity of dna repair”

“is that its activity goes down with age uh coincident and probably caused by lower levels of nad as as the animals got older”

“as they point out in this paper the main use of nad the i would say the overarching use the preferential use is the parps and cd38 not the sirtuins”

“in addition to that there's a very important DNA repair enzyme part that literally syncs up nad I mean it's like an nad sync I mean it you know so you know we're constantly having damage where does it reside that enzyme we're in the cell yeah is it nuclear it must be right yeah and the reason I ask is how do we know that these supplements that we take orally are going to actually reach their bioavailability in the place we want them okay but that said we'll come back to that after um I think it's in the nucleus I mean it would otherwise the shuttles there but I think it is so it's very important for repairing you know DNA damage and so that's one of the major sinks”

“when you damage cells with that DNA damaging agents a chemotherapy drug the cells themselves to pleat nad naturally with this enzyme called PARP 1 which is an nad consuming enzyme and that actually that's very well known that if you hit a cell with a DNA damage agent the reason that it dies is an ad depletion”

“if you're talking about nad amount levels dropping then you're looking at consumption by the parts and circuits that are consuming it for the purpose of repair damage”

“well they also have nad depletion because the sirtuins and the PARP switch is the other class of enzymes sort of using nad for the purpose of protecting DNA and telomeres and and all the things that are postulated to be important to aging and longevity they consume they're consuming the nad”

“One argument, just to make sure I understand what you're saying is, look, if you're getting older, you're going to have more DNA damage. That's just stochastic. And if your little guy that repairs it requires NAD as fuel, that would explain one reason potentially why NAD would decline as we age. Yeah. And it's certainly a sink for it. Yeah. And so the other thing is, well, if your immune system's constantly activated too, if you have more inflammation, you have all that energy is required. So NAD is being consumed more for that as well. So that's sort of another sink.”

“And then in addition to that, there's a very important DNA repair enzyme PARP that is literally syncs up NAD. I mean, it's like an NAD sync. I mean, you know, so, you know, we're constantly having damage. Where does it reside, that enzyme? Where in the cell? Yeah. Is it nuclear? It must be, right? Yeah. And the reason I ask is how do we know that these supplements that we take orally are going to actually reach their bioavailability in the place we want them? Okay. But that said, we'll come back to that after. I think it's in the nucleus. I mean, as far as I remember. It would make sense to be there, but yeah. Otherwise, it shuttles there, but I think it is. So it's very important for repairing DNA damage.”

“In addition to these enzymes that utilize the NADAH couple there's a whole series of other enzyme that actually are digesting cleaving NAD and these would be the PARPS bodus polymerase. So these are enzymes mostly involved in DNA repair.”

“How PARP enzymes consume NAD”

“One is activated PARP, and, indeed, as we age, we accumulate DNA damage. That’s been shown, especially in the brain recently, and so the idea is, by activating PARP, you constantly deplete your NAD levels.”

“for example excessive DNA damage in subsequent park1 activation have been shown to decrease nad levels to 20 to 30% of its normal levels”

“that is partly because nad promotes DNA repair capacity and its decline is associated with an increase in DNA damaging reactive oxygen species”

“nad plays a very important role in mitigating DNA damage you need nad to repair damage to DNA that is because nad is a cofactor for one of the most important enzymes involved in repairing DNA damage called PARP 1 the activation of PARP 1 requires an enormous amount of nad”

“So what about the role of NAD in repairing DNA damage? So I think about for example, PARP. Yeah. So part one is incredibly important. It's a huge NAD consumer and this is the first time I word used the word consumer this morning. So in in the N in the classic NAD co-enzyme function high energy electrons are being basically transferred onto NAD forming NADH. NADH can become can basically distribute those electrons again which reoxidizes it to NAD+. The same thing happens with NADP+ and NADPH. But when an enzyme, an NAD dependent enzyme called PARP one sees DNA damage, it basically gets excited if enzymes get excited and um it actually starts churning NAD and forming a polymer.”