Replenishing falling levels of NAD+ may be a strategy for reducing some symptoms of aging

Replenishing falling levels of NAD+ may be a strategy for reducing some symptoms of aging

[Rhonda]: Something else that really seems
to change with fasting is the NAD levels, and that’s something that, you know, your
lab has studied extensively with the sirtuins. So, maybe could you talk a little bit about… Because NAD is also extremely exciting to
me, and it’s pretty popular these days as well. [Dr. Verdin]: Yes. So, NAD has emerged as one of these critical
intermediary metabolites. Think of ketone bodies, NAD, all, I call them
currencies. I mean, so think about the organism as a country. You need to circulate energy, and NAD is one
way that our body is utilizing within the cell to convert and transfer energy. It’s almost like the Brinkman truck. It carries the money. And NAD is a hydride acceptor. While we oxidize foods, it can actually serve
as an acceptor for electron, and then it can transfer them, for example, to the respiratory
chain. So, it’s one way for the energy to be circulated
within the cell, and there’s growing evidence that its level decrease during aging. Why that happens is still one of the big mysteries,
and so this has yielded a whole approach. They’re trying to understand, first, what
are the consequences of decreased NAD levels, and one of the consequences is that enzymes
like sirtuins which rely on NAD to exert all of their beneficial activities actually function
less well. That’s what happens during aging. But, also many other enzymes that are involved
in our metabolism are relying on NAD, and so they function less well, so your intermediary
metabolism functions less well. The sirtuins, which are global regulators,
function less well. Your… Anyways, I lost my… [Rhonda]: You’re basically falling apart. [Dr. Verdin]: Yeah. Essentially, you know, everything becomes
a little less efficient. So, out of these discoveries came the idea
that maybe we should replenish the decreasing levels of NAD, and so this has yielded some
discoveries, such as nicotinamide riboside, nicotinamide mononucleotide, which are now
being taken by a lot of people with the hope that they will, you know, correct some of
these problems. One word of caution I think there is, we do
not know why these levels decrease. They could decrease because we have decreased
production of NAD, but it could also decrease because we have accelerated destruction of
NAD, which means, if it’s accelerated destruction, bringing more into it is sort of like pouring
more NAD in a leaky sink. So, I think a lot of our work right now is
trying to understand what is the cause of the decrease in NAD during aging, because
I think it will yield very different solutions. If you find that there’s a leaky sink, we’ll
work at plugging the sink versus keeping pouring water. [Rhonda]: I have a theory. [Dr. Verdin]: Yes. [Rhonda]: So, I know, you know, I did a lot
of work with DNA damage, and knowing that one of the main enzymes… [Dr. Verdin]: PARP. [Rhonda]: Exactly. I mean, if you think about… So one of the main enzymes that repairs damage
as we age, DNA damage, PARP, requires NAD, and it’s like if you’re accumulating more
and more damage as you age, you have to repair more of that damage, and the more and more
damage you’re having, maybe it’s sucking the NAD sort of like almost a triage where
you got to keep repairing that damage, so then other things like the mitochondria suffer. So… [Dr. Verdin]: I completely agree, and so there
are two major theories right now that have been proposed in terms of why does NAD go
down. 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. The second one is we all have in our body
a so-called salvage pathway for NAD, because NAD turns over. There’s this so-called salvaged pathway
that allows it to be recycled back to…so we can get NAD from the food, but also we
salvage the one that we utilize, and the salvage pathway has been shown to becoming paralyzed
while you age. There’s an enzyme called NAMPT that has
received a lot of attention. That enzyme tends to be inhibited by chronic
inflammation and a high-fat diet. So, it could be a combination of both of these
things, but it could be actually working on another mechanism, which is that there might
be accelerated destruction by other enzymes beyond par. And getting some exciting results in this
direction. [Rhonda]: Cool.


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  2. Re: the notion that NAD levels are going down a "leaky sink" — that's why many of us are now taking apigenin (found in parsley). It dampens the activity of an enzyme which destroys NAD in the body. Visit the Facebook group:

  3. Dear Rhonda,
    I’m primarily a Farmer but also trained as an advanced supplements adviser and nutritional therapist. I focus on improving mitochondrial function and their numbers as a key step to recovering from most chronic illness states. An area that I have found surprisingly effective is the use of NR, ubiquinol and PQQ in banishing anxiety and depression, sometimes very quickly. I also use Zach Bush’s Restore with high quality Probiotics as I believe our gut bacteria communications also play a vital role in positive epigenetic changes. However, I have not seen any work showing how NR might be helping anxiety and depression. Is it simple through improved RNA transcription and repair in neurotransmitter construction? Cleaner code equals cleaner less conflicted metabolism.

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