The more involved I become with stem cells and
the field of Regenerative Medicine, the more convinced I become of the
importance of the mitochondria. Many of us in clinical medicine seem to brush
over mitochondria. We now realize that many diseases are related in some way to
deficiencies of the mitochondria. Success in stem cell procedures may depend on
the health of the mitochondria. The above illustration shows the structure of
the mitochondria. Mitochondria
are rod-shaped organelles that can be considered the power generators of the
cell, converting oxygen and nutrients into adenosine triphosphate (ATP).
ATP is the chemical energy "currency" of the cell that powers the
cell's metabolic activities. Mitochondria
are often referred to as the powerhouses of the cell. They help turn the energy
we take from food into energy that the cell can use. But, there is more to
mitochondria than energy production. In
fact, only about 3 percent of the genes needed to make a mitochondrion go
into its energy production equipment. The vast majority are involved in other
jobs that are specific to the cell type where they are found. Here is another illustration of the inner
workings of the mitochondria
The mitochondria have two
membranes, an outer one and an inner one. Each membrane has different
functions. The Outer membrane allows small molecules to pass freely through the
outer membrane. This outer portion includes proteins called porins, which form
channels that allow proteins to cross. Most cellular stress
responses converge on the mitochondria. Consequently, the mitochondria must
rapidly respond to maintain cellular homeostasis and physiological demands by
fine-tuning a plethora of mitochondria-associated processes. The outer
mitochondrial membrane proteins are central to mediating mitochondrial
dynamics, coupled with continuous fission and fusion. These proteins also have
vital roles in controlling mitochondrial quality. When
cellular components like mitochondria become damaged or defective, they can be
recycled by cells through a process called autophagy, which literally means
self-eating. When mitochondria are degraded by autophagy, the process is
specifically referred to as mitophagy. Mitophagy often
occurs in defective mitochondria following damage or stress. This is
actually one of the important aspects of aging. As we age, mitophagy will
diminish resulting in increased damaged mitochondria. This has a snowball effect
in that it leads to increased reactive oxygen species (ROS), decreased
bioenergetics, and many age-related diseases. Mitochondrial damage may be the
seminal event in many different diseases. If we increase mitophagy we will slow
down aging. The following illustration shows the consequences of accumulated
The next structure to discuss is the inner mitochondrial membrane. It is
extensively folded and compartmentalized. The numerous invaginations of the
membrane are called cristae. Which are separated by crista
junctions from the inner boundary membrane juxtaposed to the outer membrane.
Cristae significantly increases the total membrane surface area compared to a
smooth inner membrane and thereby the available working space. The inner membrane is also loaded with proteins involved in electron transport and
ATP synthesis. This membrane surrounds the mitochondrial matrix, where the citric
acid cycle produces the electrons that travel from one protein complex to the
next in the inner membrane. The crista membranes contain most, if not all, of
the fully assembled complexes of the electron transport chain and the ATP
synthase. The following illustration demonstrates this concept. We see the two
membranes and subsequent ATP production. In review, at the inner mitochondrial
membrane a high energy electron is passed along the electron
released pumps hydrogen out of the matrix
space. The gradient created by this drives hydrogen back through the membrane,
through ATP synthase. As this happens, the enzymatic activity of ATP synthase
synthesizes ATP from ADP. This whole process is called oxidative
phosphorylation (OXPHOS), which is the main method and most efficient method
the body uses to make ATP. The more efficient this process the better in shape
Another structure present is the
mitochondrial ribosomes. Mitochondrial
ribosomes (mitoribosomes) perform protein synthesis inside mitochondria.
Throughout evolution, mitoribosomes have become functionally specialized for
synthesizing mitochondrial membrane proteins. Mitochondrial ribosomes resemble bacterial ribosomes and both bacteria
and mitochondria ribosomes share a slightly different genetic code from that in
the nucleus. Actually, we see that ribosomes have two parts, a large and a
Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. This genetic material is known as mitochondrial DNA or mtDNA. Mitochondria are a trans-kingdom enigma. At the molecular level, the components of Human mitochondria are assembled from viruses, bacteria, and other organisms. As such, the organelle we see in human cells today is called a trans-kingdom mixture that doesn't fully resemble any of its ancestors.
genome is built of
16,569 DNA base pairs, whereas the nuclear genome is made of 3.3 billion DNA base pairs. In keeping with its bacterial ancestry, mtDNA
is also circular and multicopy with hundreds to thousands of copies present in
every cell. mtDNA is very genetically compact and encodes only 13 proteins, all
of which are core subunits of the oxidative phosphorylation (OXPHOS) complexes.
These OXPHOS complexes, found only within mitochondria, are unique in human
biology as they are the only cellular structures formed of proteins encoded by
genes from the two separate genomes. The nuclear DNA provides around 90% of the
required proteins for OXPHOS, and the mtDNA provides the remaining 10%.
Remember that the OXPHOS complexes are responsible for ATP production.
Mitochondria are the only organelle to have their own DNA. Mitochondrial
DNA (mtDNA) is more susceptible to damage (including mutations) than nuclear
DNA. The reason for this is many folds. Most likely this is due to a lack
of histones to protect the DNA from damage. The below diagram gives a brief
explanation of histones. Histones package and order the DNA into structural units called nucleosomes. They
act as spools around which the DNA gets coiled and thus a very long strand of
DNA can be fit into a much smaller space. This is demonstrated in the
DNA damage is also caused by the proximity of mtDNA to
Reactive Oxygen Species (ROS) production. We must remember that the
mitochondria are engaged in oxidative phosphorylation which means that they are
using oxygen to produce energy. The by-product of the energy production is the
ROS. Also, mtDNA has limited DNA repair systems and limited proofreading
capacity during replication all of which can lead to accumulated mitochondrial
DNA damage. Furthermore, the mitochondrial DNA is ever changing. When a cell divides, its
mitochondria are partitioned between the two daughter cells. However, the
process of mitochondrial segregation occurs in a random manner and is much
less organized than the highly accurate process involved in nuclear DNA
division during cell replication commonly called cell mitosis. As a result,
daughter cells receive similar, but not identical, copies of their
WHAT REGULATES THE
MITOCHONDRIA? THE SIRTUIN FAMILY OF PROTEINS
Sirtuins are a
family of proteins that regulate cellular health. Sirtuins play a key role in
regulating cellular homeostasis. Homeostasis involves keeping the cell in
balance. Sirtuins can only function in the presence of NAD+,
nicotinamide adenine dinucleotide, a coenzyme found in all living cells. NAD+
is vital to cellular metabolism and hundreds of other biological
processes. Humans contain
seven sirtuins (SIRT1-7) that modulate distinct metabolic and stress response
pathways. Three sirtuins, SIRT3, SIRT4 and SIRT5, are located in the mitochondrion.
The others are found in the nucleus and one in the cytoplasm. The basic role of sirtuins, however, is that they remove
acetyl groups from other proteins. Acetyl groups control specific reactions.
They are physical tags on proteins that other proteins recognize will react
with them. Sirtuins work with acetyl groups by doing whats called
deacetylation. This means they recognize theres an acetyl group on a molecule
then remove the acetyl group, which tees up the molecule for its job. One way
that sirtuins work is by removing acetyl groups (deacetylating) biological
proteins such as histones. When the histones have an acetyl group, the chromatin is
open, or unwound. When the histones
are deacetylated by sirtuins, the chromatin is closed, or tightly and neatly
wound, meaning gene expression is stopped, or silenced. This is not that common
for the Sirtuins in the mitochondria.
Mitochondria regulation is where things get interesting. If we start
manipulating the regulation of the mitochondria then there are a whole host of
conditions from aging to chronic neuro-degenerative conditions which we might
be able to impact. Recent findings have shed light on how the mitochondrial
Sirtuin functions in the control of basic mitochondrial biology, including
energy production, metabolism, apoptosis, intracellular signaling and perhaps
most importantly mitochondrial genesis. The following diagram shows some of
What these Sirtuins
do is help in the generation of cellular energy. As high-energy
electrons derived from glucose, amino acids or fatty acids fuels are passed
through a series of protein complexes (I-IV), their energy is used to pump
protons from the mitochondrial matrix through the inner membrane into the
inner-membrane space. This is referred to as the electron transport chain.
Ultimately, the electrons reduce oxygen to form water, and the protons flow
down their gradient through ATP synthase, driving the formation of ATP from
ADP. Reactive oxygen species (ROS) are a normal side-product of the respiration
process. ROS are essentially free radicals. During cellular stress or damage,
mitochondria release a variety of signals to the cytoplasm and the nucleus to
alert the cell of changes in mitochondrial function. In response, the nucleus
generates transcriptional changes (stimulates certain genes) to activate a
stress response or repair the damage. The main function of mitochondria is to metabolize or
break down carbohydrates and fatty acids in order to generate energy.
In review, ATP
generation occurs within the mitochondrial matrix, though the initial steps of
carbohydrate (glucose) metabolism occur outside the organelle. Glucose is first
converted into pyruvate and then transported into the matrix. Fatty acids on
the other hand, enter the mitochondria as is.
ATP is produced
through the course of three linked steps. First, using enzymes present in the
matrix, pyruvate and fatty acids are converted into a molecule known as
acetyl-CoA. This then becomes the starting material for a second chemical
reaction known as the citric acid cycle or Krebs Cycle. This step produces
plenty of carbon dioxide and two additional molecules, NADH and FADH2,
which are rich in electrons. The two molecules move to the inner mitochondrial
membrane and begin the third step: oxidative phosphorylation. In this last
chemical reaction, NADH and FADH2 donate their electrons to
oxygen, which leads to conditions suitable for the formation of ATP. As an
interesting aside, the optimal ratio of NAD+ /NADH is 700/1. Greater
amounts of NADH lead to aging. NADH is considered a marker of aging. A
secondary function of mitochondria is to synthesize proteins for their own use.
They work independently, and execute the transcription of DNA to RNA, and translation
of RNA to amino acids (the building blocks of protein), without using any
components of the cell.
Another aspect that the Sirtuins control is the control of
Apoptosis. Apoptosis is a cellular process of programmed cell death. This
occurs when the mitochondrial outer membrane allows much more permeability than
normal. This will ultimately commit the
cell to death. Mitochondrial
sirtuins act in synergistic or antagonistic ways to promote respiratory
function, antioxidant defense, insulin response and adipogenesis all of which
can protect individuals from aging and aging-related metabolic abnormalities.
If these cells are not dealt with they might become senescent cells. A
senescent cell is one that should have died but continues to remain alive. The problem
with the senescent cells is that they will release a number of inflammatory
growth factors which can cause havoc in the body.
HOW DO WE KEEP OUR
We have seen the ins and outs of the mitochondrial structure and
function. The question that begs is how do we keep the mitochondria healthy? More and more research
articles demonstrate the foundational importance of optimal mitochondrial
function for health. There is a growing body of research
showing that mitochondrial dysfunction is surprisingly common and associated
with most chronic diseases. The above and below illustrations give us an idea
of how to keep our mitochondria running smoothly. The first illustration shows
some supplements which keep things running smoothly:
The second illustration shows not only specific supplements but also
classes of supplements such as polyphenols (Polyphenols are micronutrients that we get through certain
plant-based foods) and proanthocyanidins (these are chemical
compounds that give the fruit or flowers of many plants their red, blue, or purple
colors). It also stresses some lifestyle factors that can increase mitochondrial
efficiency. The specific supplements that enhance mitochondria function are
evident in the list. Let us talk specifically about some of the polyphenols. They are included in many supplements, though they're also
easy to get in your diet from foods like fruits, vegetables, teas, and spices.
There are more than 8,000 types of polyphenols. A lack of polyphenols isnt associated with specific
side effects. However, they are regarded as lifespan essentials'' for
their potential to reduce the risk of chronic diseases. This is especially true
based on their effects on the mitochondria. Research suggests that supplementation with
pyrroloquinoline quinone, also known as PQQ, can improve the number of
mitochondria in the body while enhancing their functionality. This research
also suggests that effective treatment for many diseases caused
by mitochondrial dysfunction may rest at least partly in this
coenzyme. PQQ is readily found in the soil, so it
makes sense that the best dietary sources are fruits and vegetables grown in
that soil. Fermented foods are rich in these molecules. One of the best sources of PQQ is very dark chocolate.
The above illustration shows some of the main peptides produced by the
mitochondria. Mitochondria derived peptides (MDPs) are a series of peptides encoded by mitochondrial DNA, and have similar
functions to mitochondria. They are new metabolic regulators of human body, and play a
cytoprotective role in maintaining mitochondrial function and cell viability
under pressure. Peptides
are biomolecules comprised of amino acids which play an important role in
modulating many physiological processes in our body. Peptides are
short strings of amino acids, typically comprising 250 amino acids. Amino
acids are also the building blocks of proteins, but proteins contain
more. Peptides may
be easier for the body to absorb than proteins because they are smaller and
more broken down than proteins.
Mitochondria produce numerous small polypeptides from their short open
reading frame (sORF) regions of mtDNA that have significant biological
activity. These include humanin, six small-humanin like peptides, and MOTS-c
(mitochondrial open reading frame of the 12S rRNA type-c), together termed
mitochondrial derived peptides (MDP). MOTS-c is a peptide which is called an exercise mimetic. Exercise
Mimetics are novel ways
of getting the benefits of exercising, without having to exercise. Multiple
studies have demonstrated MOTSc's ability to enhance lipid
beta-oxidation, increase thermogenic brown fat, decrease fat gain on a high-fat
diet, and improve glucose uptake during glycolysis. Various mitochondrial
peptides are produced but their use is not allowed in the USA under the current
regulations. Hopefully, this will change with time.
As time goes on we are discovering more and more about the importance of
the mitochondria and their ramifications to our health lifespan. We see that
methods to boost mitochondria efficiency are varied. But when all is said and
done. Some of the most important factors are exercise especially intermittent
high intensity training, intermittent fasting, a variety of supplements
including NAD. Low levels of oxidative stress such as is produced by
intravenous ozone therapy are also important in the proper function of the
mitochondria. We must remember that mitochondrial decay is inevitable; it cannot be prevented, at least with todays technology.
What is not inevitable is the rate of decay. The mitochondrial rate of
decay is determined by one thing: oxygen efficiency. Perhaps the following
diagram sums it all up:
We see many bad things happen when our mitochondria are not working
constantly pushing the envelope to come up with methods to improve our results
clinically. We think that our new cytokine formula may be such a game changer.
Our new formula makes use of Velvet Deer Antler. But the formula is much
different from those formulas out there both in strength and the formula
itself. It is a proprietary mix.
illustration represents the growing portion of the antler. Deer Antler Velvet
has been used in traditional Chinese medicine for thousands of years but has recently
gained popularity in Western medicine. Deer antler can enhance immune system
function, improving athletic performance, increasing muscle recovery, enhance
sexual function, improve disease recovery, enhance cardiovascular function, and
a host of other conditions.
Antler Velvet covers the growing bone and cartilage that develops into deer
antlers. The growing antler
contains a number of necessary cells, including fibroblasts, chondroblasts,
chondrocytes and osteocytes. The tips of the antlers begin as undifferentiated
mesenchymal stem cells which are transformed into cartilage. Later, the
cartilage is turned to bone, due to the effects of testosterone. Deer antler
velvet is antler that is still in its cartilaginous stage.
of the problems with Velvet Deer Antler is the purity and concentration of the
product. Our antler product is sourced from a very reliable source. Typically,
there is a concentration of 1500 mg of velvet extract per bottle. Honestly,
that will have some effects but it is not exactly what we are looking for. We
have sourced a concentration of 4500 mg of Velvet Deer Antler per bottle. This
concentration would not be legal for any professional athlete and thus we would
not use it on them. Typically, these higher concentrations will help balance
hormones and promote tissue repair. In addition to this we have actually added
certain supplements to this very potent formula. These supplements will
increase stem cell efficiency and output from the bone marrow. This combination
is totally unique to our practice and network and it is proprietary in
WHAT ARE THE MAIN COMPONENTS OF
above diagram gives some idea of the many benefits of deer extract. An
important concept that is a common theme of many research papers is that the
combination of all components of velvet antler provides a synergistic effect
that is greater than the total effect that would be achieved by the separate
use of each of its individual constituents. That means that if velvet antler is
broken down into its constituents that are used separately, their combined
effect is significantly less than the effect realized when the nutrients are
provided in the naturally combined form of velvet antler. In summary, the
effect of the complete product is greater than the summed effect of all
Let us take a
better look at exactly what is found in the antler products. Most of the antler
product consists of protein. The active ingredients include collagen, lipids,
glycosaminoglycans, minerals, and various growth factors. We will take a look at the major subgroups of
components. The first component to take a look at are the glycosaminoglycans
are complex carbohydrates.
Glycosaminoglycans (GAGs), have widespread functions
within the body. GAGs play a critical role in Regenerative Medicine. They play
a crucial role in the cell signaling
process, including regulation of cell growth, proliferation, promotion of cell adhesion,
anticoagulation, and wound repair. They are an integral component of what is
called the extracellular matrix. The extracellular matrix (ECM) is the non-cellular
component present within all tissues and organs, and provides not only
essential physical scaffolding for the cellular constituents but also initiates
crucial biochemical and biomechanical cues that are required for tissue
morphogenesis, differentiation and homeostasis.
shown GAGs exist in velvet antler in several forms including:
Chondroitin Sulphate a carbohydrate that
helps protect and rebuild degenerating cartilage and is regarded as a potent
Glycosphingolipids are compounds
involved with growth and metabolism of cells and with memory and learning
Glucosamine Sulphate is a component of
Chondroitin Sulphate and is a major component of cartilage and synovial fluid
Hyaluronic acid a substance that binds
cartilage cells together and lubricates joints. It also acts as a signaling
molecule in many biological processes.
Phospholipids the major structural lipid
of most cell membranes
Here is a good illustration of the ExtraCellular Matrix. It is the substance between the cells.
Antlers grow by endochondral
ossification, the same way that long bones do. A major non-collagenous protein,
proteoglycan, a protein substituted with glycosaminoglycan chains, occurs in
the cartilaginous tissue of antler. While its use in the antler is not
understood, it has been shown that proteoglycan in cartilage, also called
aggrecan, regulates differentiation of chondrocytes and may control calcium
concentration in the growth plates where endochondral ossification occurs. This
may have important implications when we are treating joints with regenerative
the next two illustrations show the ramifications of the ExtraCellular
Matrix and repair of various tissues. We can see why enhancing the ExtraCellular Matrix is so important in Regenerative Medicine. We can
see that these represent the pillars of regenerative cell therapy. There are
few if any other products which have these effects on the extracellular matrix.
This is certainly a huge benefit that comes with the Velvet Deer Antler
Glycosaminoglycans have a hand in all of the above repair processes. Most
products are only addressing the cellular portions of repair while the antler
products are more comprehensive in their approach.
next illustration shows how the Glycosaminoglycans are involved in the new
field of tissue engineering. In the case of tissue engineering we call the
synthetic ECM a scaffold.
GROWTH FACTORS: THE CLONES OF WHAT STEM CELLS PRODUCE
we look at velvet antler growth factors, we see a list of whos who in
the growth factor universe. Growth factors, which are generally considered
as a subset of cytokines, refer to the diffusible signaling proteins that
stimulate cell growth, differentiation, survival, inflammation, and tissue repair. The major
growth factors which are found in deer antler include Insulin Like growth
factors (IGF-1), Bone morphogenetic growth factors (BMPs), Transforming growth
factor family (TGF), Fibroblast growth factor (FGF), Platelet derived growth
factor (PDGF), Vascular endothelial growth factor (VEGF), Epidermal growth
factor (EGF), Interleukins, and a variety of other factors. When looking at the
various growth factors we realize that this appears to be similar to what is
found in a Platelet Rich Plasma (PRP) product, and for that matter stem cells
Another aspect of deer antler deals with
its Amino acid contents. Remember that amino acids are natures building blocks. Amino acids, often referred to as the
building blocks of proteins, are compounds that play many critical roles in
your body. They're needed for vital processes like the building of proteins and
synthesis of hormones and neurotransmitters. These are broken down to essential and
non-essential amino acids. Another type of amino acid is the free form amino acid. These
amino acids aren't joined together with any other amino acids in a
protein 'string'. This allows the individual amino acids to be
instantly absorbed and used by the body without digestion. All of o
Of all the growth factors the most
consequential might be IGF-1. IGF-1 is a banned substance in the world of
professional sports. The precursor of IGF-1 is Human Growth Hormone (HGH).
IGF-1 is actually the active form of HGH. It is considered performance
enhancing. In the smaller doses this is typically not an issue but in the higher
doses we are using this is a problem and across the board we will not give this
formula to any athlete in the high school, college, or the professional sports
arena. Putting this aside, why do we like IGF-1? We can see some of the
Perhaps more importantly, we need to look at
IGF-1 on the basis of cell biology. IGF-1 has been shown to enhance
the migratory response of stem cells. We must realize that the IGF-1 supplied
by deer antler is a natural form. It seems to be safer than taking the
synthetic anabolic agents which can have disastrous consequences to ones
health. The following diagram is somewhat complicated but we see the importance
of IGF-1. It will interact with the stem cell and cause the cell to go on to
repair tissue or differentiate into that tissue.
and the other growth factors can also result in a number of other health
benefits. These extra health benefits may include preservation of a persons
muscle mass, improving the functioning of the immune system, increasing bone
density thus helping to improve Osteoporosis, a valid treatment for
fibromyalgia conditions, and lastly it may help in weight loss. The bottom line
is that these growth factors are all very important in treating damaged tissue.
This tissue could be a tendon, a joint, or muscle. Remember, with the antler we
are complimenting the growth factors that are supplied by the stem cells and
the Platelet Rich Plasma. Also, by taking these supplements on a daily basis we
continue the repair process. The one small caveat that we follow is that in
those patients who have a history of certain cancers we will typically
recommend a lower dose of the antler product. We should also keep in mind that
antler products also contain small amounts of the sex hormones testosterone and
estrogen. In the right doses these are also important for regeneration.
Another related factor found in
the antler is Prostaglandins.
They are substances with varying physiologic effects, acting as a
vasodepressor, smooth muscle contraction or relaxation, inflammation and
uterine stimulation. As components of deer antler velvet, prostaglandins may
assist in the capacity of the extract to reduce the swelling associated with
arthritis and injury. They also have physiological responses in lipid
metabolism, as seen in the cholesterol-lowering effects of deer antler velvet
on laboratory animals.
antler contains many different types of amino acids. Amino acids, often
referred to as the building blocks of proteins, are compounds that play many
critical roles in your body. Amino acids are organic compounds composed of
nitrogen, carbon, hydrogen and oxygen, along with a variable side chain group.
Your body needs 20 different amino acids to grow and function properly. Though
all 20 of these are important for your health, only nine amino acids are
classified as essential. These are histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, threonine, tryptophan, and valine. Unlike
nonessential amino acids, essential amino acids are those that cant be made by
your body and must be obtained through your diet. Another type of amino acid is
a Free-form amino acid. This
refers to single amino acid that is already in a pre-digested form and ready to
be used by your body. Some nutritional products, especially amino acid blends,
contain whole proteins and large peptides (chains of amino acids), which the
body must first break down into smaller peptides and individual amino acids
before use. For faster utilization and better bioavailability, look for
free-form amino acids. We can see that all the various different types of amino
acids work synergistically. They all have their purpose.
WHAT SUPPLEMENTS ARE ADDED TO THE FORMULA TO ENHANCE THE EFFECTS?
In addition to the Velvet Deer
Antler which provides all the aforementioned compounds. There are a host of
other compounds which enhance the efficacy of the product. These include a natural matrix of herbs bounded by research and science
to help ones stem cells become more active and body supportive. The following
compounds highlight these ingredients.
found in the cell walls of certain seaweed species that is has been used
medicinally for a wide variety of health purposes. Okinawa inhabitants have a diet rich in Wakame seaweed,
which contains the highest concentrations of Fucoidan. Okinawa is also known
for its high concentration of centenarians (people who are at least a century
old), which researchers believe is linked to their fucoidan-rich diet. The
anti-aging effects are associated with Fucoidan's remarkable ability to
facilitate tissue regeneration, immune function as well as improving cell-to-
cell communication. Not only is fucoidan known for its anti-aging effects, it
is also believed to combat cancer, metabolic syndrome and other degenerative
disorders. With stem cell therapy, there is always the risk that the adult stem
cells could migrate to other areas of the body unintentionally. However, the
daily use of fucoidan has been proven to increase mobilization of stem cells to
the appropriate area/ site of injury. Not only can fucoidan point the stem
cells in the proper direction, it has also shown to improve the stem cells'
survival during the differentiation process.
PTEROSTILBENE is a stilbene molecule and demethylated
derivative of resveratrol ( it is more bioavailable than resveratrol) that is
found in antioxidant-rich foods like blueberries, cranberries and grapes. These all help to slow down
the aging process. It is an antioxidant that helps fight free
It is known to stimulate a series of pathways in the body called Sirtuin gene
pathways. The sirtuin genes have effects on a variety of other pathways in the
body. Ultimately, the Sirtuins are involved in the regulation of the
mitochondria and subsequent ATP production. Research has shown Pterostilbene
protects against memory loss, high cholesterol, high blood
and even certain types of cancer.
CARNOSINE is an important nonessential amino acid
that helps support brain, heart, and eye health. It offers antioxidant
protection from free radicals and oxidative stress, boosts endurance, aids in
the recovery process, and offers electrolyte support.
BLACK RASPBERRY EXTRACT, one of
the least known, but yet strongest anti-oxidants that insures chromosomes
retain their health and rebuild themselves to optimum health.
RHODIOLA an adaptogenic herb that can elevate your mood and
mental stamina, reduce the stress hormone, cortisol and fight
depression due to its protective effects on key mood
neurotransmitters. Rhodiola rosea extracts have recently demonstrated its anti-aging,
anti-inflammation, immuno-stimulating, DNA repair and anti-cancer effects in
different model systems. An adaptogenic herb helps the body adapt
to and resist physical, chemical, and environmental stress.
ASTRAGIN is a 100%
natural compound which is patented and promotes a healthy gut lining reducing
inflammation in the intestinal lining and increasing absorption of nutrients. AstraGin has the ability to increase the assimilation of
important amino acids which increase nitric oxide levels in the human body,
making it the perfect performance enhancer when taken
pre-workout. Higher levels of nitric oxide result in enhanced blood
flow to the muscle which leads to better pumps, muscular contraction, and
improved nutrient transportation. AstraGin also aids in glucose absorption so
having this pre-workout ensures that you have sufficient energy levels whilst
THE FINAL QUESTION HOW DOES THE ANTLER PRODUCT GET TO
WHERE IT IS NEEDED?
have the absolute best formula on paper but the question is will it work? When
we evaluate medications and supplements a very important aspect to consider is
what we call the pharmacokinetics of the product. This concerns the science of
how the drug moves around in the body. Unfortunately, on paper many compounds
seem very promising but in real life are a failure. The main reason for this is
that they cannot be absorbed by the body.
The mode of
absorption of the antler product is what is referred to as sublingual. This
means it is absorbed under the tongue. This is many times a very effective mode
of absorption. It bypasses the gut and goes directly into the bloodstream where it is needed. The components are not broken down.
Also, in the saliva are very small particles called exosomes which can be
considered a rising star in drug delivery. Saliva is a very rich source of
exosomes. Thus, we have a very efficient method of delivering the velvet
components in a safe and reliable manner.
If we were to
undertake the task of trying to design a complete supplement to utilize in
Regenerative Medicine and Stem Cell therapy, Velvet Deer Antler would be at the
top of our list. It has most of the ingredients needed for success.
Furthermore, there is a very efficient way to deliver the goods to the cell
where they are needed. Deer antler will not be the only modality we will use,
but it certainly has an important place on our mantle. We are constantly
working to push the envelope and I suspect more advances will come.
The above is the title to a new article published by Dr. Sinclair and his group from Harvard. I had the good fortune of being sent this paper by an associate of mine. The paper is still not officially published but it drives home some significant points. David A. Sinclair, Ph.D., A.O. is a Professor in the Department of Genetics and co-Director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. I hold Dr. Sinclair in great esteem for his work on understanding why we age and how to slow its effects. Dr. Sinclair has taught us about Resveratrol and more recently NAD and its supplements.
The paper contains an excellent synopsis of the relationship between Covid-19 and the aging immune system, namely immunosenescence. It gives a comprehensive breakdown on the failures of the innate and acquired immune systems. These are the two major components of our immune system.
The paper itself is a rather technical one and I will try to discuss it in layman terms. First off, let’s take a quick look at some of the benefits of the NAD to our bodies. We can see the effects are wide ranging.
Among other things we see in the above diagram that NAD affects both immunity and inflammation. Many of the other effects indirectly affect immunity and inflammation. We now know that as we age there is steady increase in the abundance and activity of NLRP3 protein. NLRP3 which is a major protein component of an inflammasome. Inflammasomes are a group of protein complexes found in the cytoplasm of the cell. They are formed to mediate host immune responses to microbial infection and cellular damage. NLRP3 is responsible for a host of problems including auto immune diseases, metabolic disorders, and severe damages from infections such as a cytokines storm. You will definitely be hearing more about NLRP3 as time goes on. It is on the cusp of major scientific research. Now just how does NAD come into the picture when dealing with the NLRP3 inflammasome? The real crux of the matter is that the NLRP3 activation is under the control of SIRT2 gene. Sirtuins are a family of proteins that regulate cellular health. SIRT2 is a member of the NAD+ dependent sirturn family of deacetylases enzymes. If NLRP3 is activated and at the same time one is exposed to Covid-19 virus the combination may cause quite a few problems to the patient. However, it one maintains NAD levels and there is a good chance of alleviating Covid 19 symptoms by the Sirtuin suppression of the NLRP3 inflammasome.
In 2013, Sinclair further reported scientific studies that demonstrated NAD fuels the activity of a group of proteins called the sirtuin proteins, including SIRT2. Sirtuins are a fascinating family of enzyme-genes. It is now clear that sirtuins are involved in the regulation of many fundamental biological processes throughout the body. The following is a diagram of the various Sirtuin genes and where they are found in the cell.
If we look in the above diagram we see the SIRT2 gene which is located in the cell cytoplasm. The cell cytoplasm also contains the NLRP3 inflammasome. The bottom line is if the SIRT2 gene is activated it will squash the actions of the NLRP3 and the Covid-19 virus will have a harder time getting established.
What has been a common thread in many patients infected with the Covid-19 virus is that co-morbidities seem to dramatically affect the symptoms of the patient. One of the biggest co-morbidities seems to be obesity. It is well known that obesity will increase the complications of the Covid-19. Obesity will dramatically increase the activity of the NLRP3 inflammasome. Thus, anyone who is obese should absolutely be taking NAD supplements and possibly even take it intravenously. NLRP3 inflammasome is found in the cytoplasm of the cell while many times when we are dealing with infections it is the cell receptors on the cell surface membrane that detects the infection and elicit a response. Multiple studies show that calorie restriction and exercise-mediated weight loss in obese individuals with type 2 diabetes is associated with a reduction in adipose tissue expression of NLRP3 as well as with decreased inflammation and improved insulin sensitivity. Remember the control of NLRP3 activity is under the direct control of SIRT2, which is dependent upon NAD and its derivatives. Studies have shown old mice, especially those deficient in SIRT2, have accelerated inflammaging, along with decreased glucose tolerance and increased insulin resistance. So, the bottom line is take your NAD!!
THE BIOLOGIC CLOCKS OF AGING
The second part of the article talks about BIOLOGICAL CLOCKS. We have developed a number of biological clocks that have been shown to predict human health and longevity more accurately that chronological age. These biological clocks are based on various aspects of aging. There are at present any number of approaches to measuring biological age, the burden of cell and tissue damage that leads to dysfunction.
THE EPIGENIC CLOCK OF AGING
The first clock to discuss is the EPIGENETIC CLOCK. Epigenetic age seems like a concept pulled from a futuristic science-fiction movie where a drop of blood is fed into a machine, in which an algorithm churns through an accumulation of chemical groups coating a strand of DNA and spits out an individual's true age reflecting a lifetime of experiences and exposures. In simplistic terms, epigenetics involves putting a methyl group on a DNA strand. Methyl groups are organic molecules. What we are really dealing with is called DNA methylation. DNA methylation occurs when a methyl group is added to a DNA strand. DNA methylation is a tool to typically lock genes into their off position. Aberrant DNA methylation, which is a nearly universal finding in cancer results in disturbed gene expression. DNA methylation is modified by environmental factors such as diet that may modify cancer risk and tumor behavior. Abnormal DNA methylation has been observed in several cancers. These alterations in DNA methylation may play a critical role in cancer development and progression. Dietary nutrient intake and bioactive food components are essential environmental factors that may influence DNA methylation. In recent decades, researchers have learned a great deal about DNA methylation, including how it occurs and where it occurs, and they have also discovered that methylation is an important component in numerous cellular processes. The following diagrams illustrate some of these concepts:
We are able to see from the above diagram that healthy lifestyles cause age deceleration. While the opposite is true with unhealthy lifestyles. Another way of looking at things is found in the diagram below. The blue arrows represent anti-aging while the red arrows represent pro-aging effects on blood chemistry.
Pictorial summary of our main findings. The blue and red arrows depict anti‐ aging and pro‐aging effects in blood respectively. The two clocks symbolize the extrinsic epigenetic clock (enhanced version of the Hannum estimate) and the intrinsic epigenetic clock (Horvath 2013) which are dependent and independent of blood cell counts, respectively.
What does this boil down to? Age-associated changes to the epigenome, essentially our DNA, have profound effects on the immune system, including T cell function, cytokine production and macrophage (white blood cell) pattern recognition. DNA methylation is believed to set the pace of the aging clock in several of our tissues, including hematopoietic (Red and White Blood) cells of the immune system. Recently there was a study that restoration of the thymus gland using a drug cocktail of metformin, growth hormone and DHEA (dehydroepiandrosterone) led to the reversal of features of immunosenescence which is the decline in the immune system that comes with aging. This is actually a monumental study that may have profound implications on our health. Most of the existing research suggests that DNA methylation relies at least in part on folate, vitamin B-12, vitamin B-6, and choline, in addition to other vitamins and minerals. Increasing your intake of these nutrients may help to support DNA methylation, preventing certain genes from being expressed. One parting thought is that the pattern of methylation in DNA has been shown to be an even better predictor of not just biological age, but also lifespan and healthspan.
THE GLYCOSYLATION CLOCK
The above diagram is a very real biological clock. One method of measuring the glycosylation clock can be measured be a simple blood test which is called the A1C hemoglobin blood test. This is a common blood test performed in diabetic patients. It gives a snapshot of blood glucose levels over a period of time. It gives a picture of the amount of glucose that is binding to the hemoglobin protein molecule. The higher the number of the A1C the greater the number of glucose molecules attached to the hemoglobin protein and thus the worst the control of the diabetes.
The glycosylation clock is clearer than most biological clocks. It is a very direct assessment of the chronic inflammation associated with aging. In more technical terms, Glycosylation is the enzymatic process by which carbohydrates called glycans are attached to proteins or lipids, typically on the cell surface or in the bloodstream. An individual's repertoire of glycans, a notable example being the type of N-glycans attached to immunoglobulins, changes with age and environmental factors such as such as smoking and poor diet. The type of glycans attached to IgGs affects their pro- and anti-inflammatory properties. IgGs are a type of antibody representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. It is instrumental in fighting most infections. The real problem with glycosylation is the production of what are called “advanced glycation end products” (AGEs). This occurs when the sugars bind to proteins causing a host of problems as can be seen in the following diagram. Advanced glycation end products (AGEs) are proteins or lipids that become glycated as a result of exposure to sugars. They are a bio-marker implicated in aging and the development, or worsening, of many degenerative diseases, such as diabetes, atherosclerosis, chronic kidney disease, and Alzheimer's disease. Animal-derived foods that are high in fat and protein are generally AGE-rich and prone to new AGE formation during cooking. In particular, grilling, broiling, roasting, searing, and frying propagate and accelerate new AGE formation. The following diagram shows the variety of the clinical manifestations of glycosylation.
GLYCOSYLATION’S MANY DEADLY SINS
As we can see these are very damaging to various systems in the body. Remember, glucose is one of the main driving forces in the production of AGE products! Another great diagram of the effects of AGEs is found in the following diagram. Realize that AGEs and glycosylation can lead to significant musculoskeletal symptoms.
THE IMMUNE CLOCK
The last clock to mention is the IMMUNE CLOCK. There is an old saying that we are as old as our immune system. There is some good scientific literature that the immune system may be made “younger” by among other things a type of cell found in the body called a V cell. Here is the study from a research journal which explains this concept.
What the V cells do is extend the Telomere length of the cells of the immune system. Telomeres are the ends of the DNA of the cells. When cells reproduce they lose a snippet of DNA which is called the telomere. The smaller the DNA length typically the less effective the cell becomes. Well the V cells restore the length of the DNA telomere and thus increase the effectiveness of the cell. They are literally making the cell take on younger characteristics. V cells are found in each and every one of us. The trick is to activate them (which we have mastered) to than let them perform their good deeds.
When all is said and done what effect will this article have upon myself? The answer quite a bit. I am already a big believer in NAD and I am becoming more to cognizant of Nature’s Biological Clocks and how we can manipulate them. I practice what I preach. V cells have been on my horizon and will continue to remain there. Hopefully this article has opened your eyes on the “Biological” clocks in the body and how we can influence them with certain life style changes, procedures, and medications such as NAD which I consider one of nature’s elixirs. Remember time always moves forward but there is no reason why we cannot slow down its progression.
ONE FINAL THOUGHT IS THAT I AM PROUD TO SAY IS THAT OUR OFFICE WILL BE ONE OF THE FIRST TO OFFER A BLOOD TEST FOR DNA METHYLATION. IT IS THE MOST ACCURATE, REVOLUTIONARY, BIOLOGICAL AGE PREDICTOR.
THE TEST UTILIZES STATE-OF-THE-ART TECHNOLOGY AND A POWERFUL ALGORITHM WHICH LOOKS AT SPECIFIC LOCATIONS ON YOUR DNA, ALLOWING US TO PREDICT YOUR BIOLOGICAL AGE! ONCE WE HAVE THAT INFORMATION THAN WE CAN START MAKING RECOMMENDATIONS.
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