NAD the topic of today NAD+
it's the youth molecule depleted by inflammation and for those of you who say well Doc you're
pronouncing it wrong it should be inflammaging sorry maybe I'll use one way one time and the
other the other what is NAD in the first place the long term is nicotinamide adenine dinucleotide
easy for me to say huh it's a coenzyme found in all living cells it promotes cellular
energy production and metabolism it exists in two forms NAD+ and NADH you may recognize that if
you get into your high school chemistry what we're talking about here is a difference of an electron
NAD+ picks up an electron to become NADH and NADH donates an electron to become NAD+ now
where does that happen mostly in the mitochondria if you look at this image here this orange and
yellow thing that's a obviously oversimplified image of a mitochondria again those of you who
took maybe high school bio I mean well high school but for sure college-level biochemistry
maybe some of this stuff will start coming back remember glycolysis and then the Krebs
cycle where you go into the mitochondria the mitochondria starts taking a carbon
off of that TCA tricarboxylic acid cycle as it takes those carbons off and replaces those with
those carbon-carbon bonds with electron bonds you get energy it pulls energy out of that molecule
that's what gives us energy and that process uses oxygen the fact that it uses oxygen makes it much
more it creates a huge advantage for us over other life forms like yeast yeast can't do that so out
of a typical glucose molecule yeast will pull six energy units whereas humans using oxygen and this
tricarboxylic acid TCA cycle will pull like 36 and I've gone off script here let me go back on
script this continuous give and take of electrons generates energy used to power various biological
processes NAD+ has gone from being a metabolic player to a crucial substrate required by sirtuins
now you may remember that term and that starts to get us to David Sinclair David Sinclair
an Australian who moved to the US to work at Harvard and has become a globally acknowledged
anti-aging expert he's done a lot in terms of the discovery of sirtuins and they are proteins
that help us control longevity there are lots of supplements aimed at restoring NAD+ to
youthful levels like NMN which you'll hear more about in this discussion today now which ones
actually work this is one of the places where I'd say this is not really an advertisement for NMN
or for David Sinclair I've personally tried NMN I use niacin a lot still in my patients and
personally I've used some other supplements all of which revolve around this niacin
base NAD which is a niacin base as well unfortunately NAD+ levels decline with
age that's what the problem is and that's why everybody keeps circling around the mitochondria
and NAD which is part of the major substrate or fuel or energy transfer molecule that's used
by the mitochondria here's the title of the article by the way senescence cells that's old and
dying cells promote tissue NAD+ decline during aging via the activation of a CD38+ macrophage
that sounds extremely technical we're going to get a little bit technical but we water this down
a whole lot much more for our level viewer and our level viewers not really a sixth grader but
more of a health nut somebody who wants to live a long time and knows that if they depend on their
local primary care doc they may not be getting the information that they need so this is the level of
information that we're presenting it's out of Nature Metabolism and as you know the Nature
magazines are globally some of the absolute best magazines for science in the world today
it's Nature Metabolism November 2020 and it supports this discussion of NAD+ degradation
Buck Institute you may have heard of Buck Institute that's where Dale Bredesen you
know The End of Alzheimer's guy he does a lot of work there at the Buck Institute those researchers
at Buck Institute have identified inflammaging or age-related chronic inflammation as a driver
of NAD+ decline mechanism one aging and bouts of inflammation lead to the accumulation
of pro-inflammatory you know or inflammatory M1-like macrophages a certain type of immune
cell that's what a macrophage is metabolic tissues like liver and visceral fats so it's these immune
cells as you see a picture over here these CD38 M1 macrophages impacting and being impacted by
these senescent cells to increase inflammation increase NADase an enzyme impacting NAD's
activity in other words and then usually when you see in a something "are" in it it's talking
about an enzyme and it's also talking about an enzyme that breaks something down so NADase
is an enzyme that breaks down NAD so guess what that final step is a decrease in NAD now these
macrophages express a protein called CD38 while CD38 is just one of several NAD-consuming enzymes
it's a major consumer of NAD+ here's another mechanism aging also leads to the accumulation
of senescent cells now when the cell is stressed or the DNA is damaged the cell stops dividing to
make new cells this is called cellular senescence it's designed to be a proactive or a protective
measure against cancer and other diseases however senescent cells increase with age if
they accumulate and they're not cleared ironically they lead to cancer now speaking of David Sinclair
and aging he wrote a book called Lifespan I did a series on that book with about there were
about nine videos in that series one of those videos focuses specifically on senescence cells
senescent cells do play a positive role it's a protective role it's helping those cells and
other cells shut down when sometimes cells need to shut down in order to protect themselves cancer is
a perfect example cancer is an overactivity of growth and replication senescence helps
slow that down obviously you don't want too many cells taking that kind of vacation slowing down
they can also influence other cells to do exactly that so you may want to take a look at that
series that I did on Lifespan very very interesting I've got a major interest in
anti-aging so I'm very interested in a lot of the stuff in that book it was a great book and a
lot of the stuff that Dr. Sinclair does senescent cells also produce inflammatory proteins called
SASP SASP drives in M1-like macrophages to proliferate in other words replicate multiply in
mechanism 1 these macrophages drive an increase of CD38 remember that protein that breaks down
NAD and later resulting in a decrease of the NAD+ according to Dr. Anthony J. Covarrubias
one of the authors and a postdoctoral fellow at of the Verdin lab these inflammatory proteins
in the SASP induce macrophages to proliferate in other words it's there's a spiral effect here
more macrophages producing CD38 more creating more senescent cells more senescent cells creating the
CD38+ macrophages so like many many things in the body like clotting like some inflammatory
processes like this inflammatory process there's a spiraling effect a little bit creates more and
more and more it's a maladaptive process but drugs that target the SASP for CD38 may offer
us another way to deal with the decline of NAD+ so we've been talking about
the mechanism for aging and disaster and bad stuff happening why have we been talking
about it to get to that sentence are there ways that we can impact it now obviously we
as our society is we go too quickly to drugs and one of the problems that I have with Dr. Sinclair
is that he goes to a supplement he wants to give a pill he's been quoted as saying
that many many times I'm going to give you a pill that will keep you from getting sick
continue to get great feedback regarding the webinars and here's why you know on the
internet when you hear a webinar you expect for somebody to try to sell you something
we're not doing that we're trying to tell you something people are coming in with their labs
from Quest inflammation panel OGTT insulin survey response and then they're finding out do I have
inflammation do I have insulin resistance and where does that fit in terms of other folks
we're getting ready to start one for CIMT as well so again people are really
excited about finding out their own status looking forward to seeing you there thanks