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September 29, 2014. Internal development on Grey Defence®GeneJOLT! Professional Strength has finally been completed. You will find full details below. Be advised, this is an early stage developmental product and a ‘double blind, placebo controlled, randomized study’ on it has not been conducted, nor are there any plans to do so. Instead, we will be conducting an Open Label Trial (OLT) (similar to what we did for Grey Defence®XTREME) prior to the general release between July and August 2015. You are all welcome to participate in the OLT, which commences on November 1st 2014. Also please note, GeneJOLT! is a dietary supplement for healthy adults. It is not recommended for children, or for adults with cardiovascular or liver disease, undergoing cancer treatment or using medications for same. GeneJOLT! should not be used for the cure, mitigation, treatment, or prevention of any disease and was not design for such usage.
GeneJOLT! picks up where XTREME lets off. XTREME simply removes the hydrogen peroxide from the base of the hair follicle, it does not try to repair damage cells. With no hydrogen peroxide to bleach the hair, the hair follicle is able to revert to its normal colour over time, assuming it still has active melanin producing cells.
Follicular melanocyte stem cells (FMSC) are responsible for the pigmentation of hair follicles and are the primary targets of GeneJOLT!, with the remaining eukaryote cells being secondary targets.
Mitochondria are our cells’ power plants. They are where cellular respiration takes place and tend to face functional decline with age. The mitochondria of FMSC are no different; they also degrade with age. FMSC are responsible for colouring our hair, and a decline in their mitochondria has important negative implications for greying [Graying: gerontobiology of the hair follicle pigmentary unit]. Additionally, chromosomal telomeres control a cell’s ability to divide and for fast dividing cells like FMSC, declining telomere length also has important negative implications for greying.
This type of greying in which our cells experience oxidative damage we refer to as genetic greying [Genetic analysis of ageing: role of oxidative damage and environmental stresses]. This is not a statement about the inheritance of a particular trait from your ancestors, but a mechanistic description of the greying pathway – thus the name of our tool to fight it GeneJOLT!.
The functional objectives we set for GeneJOLT! takes it beyond the conversation on reversing grey hair and into the realms of fighting systemic biological aging. Yes GeneJOLT! is designed to reverse greying due to cellular aging, but it was designed to be much more than just a grey hair pill.
The design goal for GeneJOLT! is the systemic rejuvenation of our cells including FMSC, in an effort to turn back our biological clocks.
GeneJOLT! attempts to achieve its design goal by employing a number of pathways: first, it seeks to strengthen the liver to promote overall toxins elimination and ameliorate immunosenescence (the decreased function of the immune system with age) by strengthening the immune system via promoting the increase in natural killer (NK) cells, T cells, T Helper cells, Macrophages as well as a range of Cytokines signalling compounds. Next it seeks to neutralize superoxides, a potent free radical that damages cells and can lead to age related diseases. Third, GeneJOLT! works to extend chromosomal telomeres length to improve cells’ ability to replace aging members via cell division. Fourth, GeneJOLT! seeks the rejuvenation of cellular mitochondria to make our cells more resistant to reactive oxygen species (ROS), which are harmful to cells. Fifth, it mutes the physiological responses to everyday life stresses (psychophysiological stress) to reduce the negative consequences of chronic stress in cellular aging. Finally, of course, it removes hydrogen peroxide from the base of the hair follicle in a similar manner as does Grey Defence®XTREME.
To understand the specifics of the pathways outlined above requires a detailed understanding of the functional ingredients whose therapeutic actions provides GeneJOLT! with its ability.
MICROPARTICLES
However, before discussing the functional ingredients, we will take a slight detour so as to discuss a brand new technology being introduced with GeneJOLT!. This is the extensive use of particle science; specifically, the use of microparticles, to promote acid resistance, enhance bioavailability and extended release capabilities to several difficult to handle ingredients included in GeneJOLT!.
Microparticles (microspheres) are particles with a dimension between 1 μm > 1000 μm. Where μm = microns. 1000 μm is equal to a millimeter.
In GeneJOLT! we use the copolymer poly(lactic-co-glycolic acid) (PLGA) to make microparticles.
PLGA was chosen because it is one of the most studied biocompatible, biodegradable copolymer used in in-vivo drug delivery; it is pH nonreactive – making it an excellent acid resistant encapsulant for acid sensitive ingredients. PLGA materials biodegrades over time in blood serum, this allows for the development of extended release formulations. These copolymers also have the added benefit of enhancing intestinal absorption by sticking to the mucous membranes of the intestines [Mucoadhesive Drug Delivery: Mechanism…]. PLGA also has FDA approval.
THE MECHANICS OF GENEJOLT!
As mentioned previously, to best understand the way that GeneJOLT! attains its functional objectives, we need to understand the bioactive ingredients in the formula. In alphabetical order, the key functional ingredients are Cycloastragenol, Epigallocatechin gallate, Glutathione, Honokiol, L-Theanine, Nicotinamide Riboside, Pyrroloquinoline quinone, Silybin, Silymarin and Vitamin C.
Of course the ingredients currently in Grey Defence®XTREME are also present in GeneJOLT! and at the same concentrations. We however will not be covering them in this post since they have already been covered elsewhere.
Active Hexose Correlated Compound (AHCC)
AHCC is a specialized compound extracted from the hybridization of several subspecies of mushrooms (Shiitake and Basidiomycota). Like the extracts of Ganoderma lucidum (see below), AHCC is included as an immunomodulator and tumericidal agent. AHCC boost immune response to abnormal cell growth, infectious agents and protects against age related health issues [Effects of active hexose correlated compound (AHCC) on the frequency of CD4+ and CD8+ T cells producing IFN-γ and/or TNF-α in healthy adults].
Cycloastragenol
Cycloastragenol is an extract from the root of Astragalus Membranaceus. Cycloastragenol is a telomerase activator [Dietary safety of Cycloastragenol from Astragalus…].
Telomerase
is an enzyme that has the ability to add DNA sequence repeats (“TTAGGG”) to eukaryotic chromosomes; in short, it lengthens telomeres. The length of a cell’s telomeres is one of the key biological markers of aging, since telomeres gets progressively shorter with age. The longer are the telomeres, the better able a cell to sub-divide and produce newer versions of itself [How stem cells age and why this makes us grow old].
To understand why this is important for GeneJOLT!, we need to understand the process by which the hair produces color throughout each new growth cycle (anagen phase).
Sitting at the base of each hair follicle are several undifferentiated follicular melanocyte stem cells (uFMSC). At the start of a new anagen phase, these uFMSC splits into two to create a daughter cells. The daughter cells then moves up the hair follicle traveling along the hair shaft as it grows. The new daughter cells becomes differentiated producing the melanin pigment that gives the hair follicle its color.
In the meantime, the original half – the uFMSC – remains at the base of the hair follicle awaiting future Anagen phases to split again and produce more differentiated daughter cells that can colour future hair shaft.
The natural aging process of the uFMSC is such that every time it divides, its telomeres shorten, until it gets to a point where it can no longer divide. Once it can no longer divide to produce differentiated daughter cells, then the follicle loses its ability to colour the hair [Aging, graying and loss of melanocyte stem cells…].
Of course, this shortening of telomeres process is sped up by damage caused by reactive oxygen specie reactions (ROS) like hydrogen peroxide and superoxides [Oxidative Stress, Oxygen Free Radicals and Telomere Shortening…].
GeneJOLT! employs Cycloastragenol – a telomerase activator – in its functional objective of directly stimulating the growth of telomere length, so that uFMSC can continue to produce differentiated daughter cells that can colour the hair shaft during future anagen phases [Telomerase reactivation reverses tissue degeneration…].
While it has been demonstrated that Cycloastragenol extends telomeres, research has also shown that it under goes extensive first pass hepatic clearing by the liver, as a result only around 8% of the ingredient actual gets into the blood stream [In vitro Intestinal Absorption and First-pass Intestinal and Hepatic Metabolism of Cycloastragenol…]. To optimize this ingredient’s bioavailability, each serving of GeneJOLT! contains 10 mg of Cycloastragenol embedded in a PLGA microsphere matrix with a mean diameter measuring approximately 10 μm.
Epigallocatechin Gallate
GeneJOLT! contains the catechins Epigallocatechin gallate, Epicatechin gallate, Gallocatechin gallate, with Epigallocatechin gallate being the largest composition. Catechins are antioxidant extracts from green tea and have several demonstrated therapeutic functions. In GeneJOLT! these catechins are included for their ability to unravel the DNA of abnormal cell growth.
This is important for our formulation because theoretically speaking (there has been no evidence to support this hypothetical) Cycloastragenol may promote the growth of benign tumors (abnormal cell growth) by extending their telomeres, causing them to become immortal. Green tea catechins have been shown to arrest abnormal cell growth [Green Tea (Camellia Sinensis) Extract and Its Possible Role…].
Glutathione
Reduced Glutathione (GSH) is an important antioxidant that prevents damage to cellular components caused by reactive oxygen species such as free radicals and peroxides [The changing faces of glutathione, a cellular protagonist…].
The early generation of reactive oxygen species such as hydrogen peroxide during mitochondrial inhibition contributes to cell damage and reduce Glutathione serves as a first line of defense in their removal [Hydrogen peroxide removal and glutathione…]. Glutathione also has the ability to regenerate other antioxidants and as a result is sometimes referred to as the master antioxidant.
To optimize this ingredient’s bioavailability,Setria branded Glutathione is used in GeneJOLT!.
Honokiol
Honokiol is an extract from the bark, seed cones, and leaves of trees belonging to the genus Magnolia. It has the same function in GeneJOLT! as the green tea catechins. Essentially arresting the growth of abnormal cells [Honokiol, a Small Molecular Weight Natural Product, Inhibits Angiogenesis in Vitro and Tumor Growth in Vivo…].
L-Theanine
There are many articles on our website discussing oxidative stress but none addressing everyday life stresses (psychophysiological stress) and their impact on aging, hopefully this section rectifies that a bit. Psychophysiological stress may affect cell aging through at least three non-mutually exclusive pathways: 1) triggering immune cell function or distribution, 2) triggering oxidative stress responses, 3) reducing telomerase activity [Accelerated telomere shortening in response to life stress…].
It is our belief that for greying, the most important effects are the combined oxidative and reduced telomerase activity on fast dividing cells such as uFMSC. This combination results in the accelerated declined of the telomeres length in the uFMSC preventing it from creating colour producing daughter cells.
L-Theanine is an amino acid extracted from green tea and has been clinically shown to reduce anxiety caused by psychophysiological stress [The effects of tea on psychophysiological stress responsivity…].
GeneJOLT! is our first product purpose built to address psychophysiological stress. It employs the SunTheanine brand of L-Theanine at a concentration of 200 mg per serving.
Nicotinamide Riboside
Nicotinamide Riboside is a precursor of Nicotinamide Adenine Dinucleotide (NAD), and is a source of Vitamin B3. It is normally found in milk. Commercial quantities are synthesized from organic chemicals.
NAD has several essential roles in metabolism. It acts as a coenzyme in redox reactions (electron donation) and as a substrate for a group of enzymes called Sirtuins that use NAD+. “The NAD requirements for Sirtuins suggest that there is a link between aging and metabolism, and a boost in Sirtuin activity may in part explain how calorie restriction extends life span” [Sirtuins in aging and disease].
Sirtuins are a special class of cellular proteins with major roles in mitochondria biogenesis, for example Sirtuin 1 takes part in mitochondrial biogenesis, glucose regulation and the protection against age related disease [Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial…].
By adding Nicotinamide Riboside to GeneJOLT!, we hope its consumption will increased the levels of NAD+ in the mitochondria, resulting in the improvement of mitochondrial performance, energy metabolism and cell rejuvenation [Effective treatment of mitochondrial myopathy by Nicotinamide Riboside…].
Rhodiola Rosea
Rhodiola Rosea is an adaptogen that assist in the handling of mental stress. It increases resistance to stress, without disturbing normal biological functions [Rhodiola rosea in stress induced fatigue—a double blind cross-over study…].
Silybin & Silymarin
Overtime the body naturally collects toxins due to metabolic activity, environmental pollution, lifestyle choices and a myriad of other causes. The liver is a key organ in the elimination of most of these toxins. Therefore, keeping the liver well tuned and working optimally is of vital importance – especially as we age.
Silybin & Silymarin are extracts from Milk Thistle that’s been shown to protect liver cells against toxins and support detoxification of the body [Comparative study of the hepatoprotective effect of silymarin and silybin…]. Further, in laboratory experiments, Silymarin was shown to demonstrate substantial protective effect and free radical scavenging ability against hydrogen peroxide induced oxidative stress damages [Silymarin Protection against Major Reactive Oxygen Species…].
Superoxide Dismutase
Cellular respiration is the process in which nutrients are converted into useful energy in the mitochondria. Superoxides are free radicals that are created during cellular respiration. Superoxides are extremely damaging to cells because they steal electrons, which can lead to cell aging (senescence) or even cell death (apoptosis).
Superoxide dismutase (SOD) is an enzyme found in all living cells (systemic enzyme) and it serves as a first line defence against superoxides [Induced Overexpression of Mitochondrial Mn-Superoxide Dismutase Extends…]. SOD neutralizes superoxides by being an electron donor, converting superoxides into hydrogen peroxide, which in turn is broken down to water and oxygen by the enzymes Catalase and Glutathione Peroxidase.
Figure 5: Superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) are the main endogenous enzymatic defense systems of all aerobic cells. They give protection by directly scavenging superoxide radicals and hydrogen peroxide, converting them to less reactive species. SOD catalyzes the dismutation of superoxide radical (•O2) to hydrogen peroxide (H2O2). Although H2O2 is not a radical, it is rapidly converted by fenton reaction into •OH radical which is very reactive. GPx neutralizes hydrogen peroxide by taking hydrogens from two GSH molecules resulting in two H2O and one GSSG. GR then regenerates GSH from GSSG. CAT the important part of enzymatic defense, neutralizes H2O2 into H2O.
It is estimated that approximately 2% to 3% of the oxygen consumed by aerobic cells is diverted toward the generation of superoxide free radicals and hydrogen peroxide [Hydroperoxide metabolism in mammalian organs]. This is a significant amount of oxygen diversion and it gets worse with age as the becomes less efficient.
As we get older, our bodies start reducing the amount of systemic enzymes it produces. This of course eventually leads to cellular aging [Superoxide dismutase evolution and life span regulation…]. Therefore supplementation is an important route to maintain a healthy balance. Unfortunately enzymes are very sensitive to stomach acid and as such must be given acid protection when taken orally.
Superoxide dismutase is an intracellular enzyme not generally found in blood serum, as a result, it under goes hepatic first pass clearance when consumed orally and very little if any enters the blood stream – even when it is protected from stomach acid. In fact, serious SOD therapies are generally administered parenterally [Protection against oxygen toxicity by intravenous injection…].
Biocompatible, biodegradable, acid nonreactive materials such as PLGA provide an attractive solution to the first pass clearance problem [Biodegradable Microspheres as Carriers for Native Superoxide Dismutase…]. Encapsulating SOD proteins into PLGA microparticle matrixes neutralizes first pass clearance. Further such encapsulations provides an extended dose release capability, allowing for versions of SODs with half-lives measured in days, weeks or even months, as opposed to the minutes of non-encapsulated SOD.
To optimize Superoxide dismutase bioavailability, it was embedded in a PLGA microsphere matrix with a mean diameter measuring approximately 10 μm. This we call SuperSODTM.
More specifically SuperSODTM consist of Cu-Zn SOD (SOD1) and Mn SOD (SOD 2) that are combined in a specific proportion and embedded into a biodegradable, biocompatible copolymer to extends its bioavailability and half-life in the human body.
Triterpenes & Polysaccharides (Ganoderma lucidum Extract)
Triterpene & Polysaccharides extract provides a broad spectrum of action including antioxidant, immunomodulation and others. It is in the formula on the same basis as AHCC, the green tea catechins and Honokiol, and that is as a immunomodulator and tumoricidal agent [Anticancer Effects of Ganoderma lucidum: A Review of Scientific Evidence]. For clarification, GeneJOLT! should not be used for the cure, mitigation, treatment, or prevention of any disease, this includes cancer.
SUMMARY
The above overview in detail provides a pretty solid accounting of the work we’ve been doing to develop GeneJOLT!, a powerful tool that can rejuvenate follicular melanocyte stem cells, as well as, other eukaryote cells in our bodies. Thereby delivering to our customers, what we believe to be a powerful weapon not only in the anti-greying fight, but also one against biological aging.
The next stage in the developmental cycle for GeneJOLT! is a limited product release starting November 1st 2014. The available supply of GeneJOLT! is limited because though cutting edge, microparticle technologies are not very scalable. This places a limit on the amount of product that can be manufactured in any given time period. We are calling this limited release the Advance Trial Group (ATG) release. To be in on the ATG, please visit the link below. Please note, we do expect the ATG to be oversubscribed, to avoid disappointment you should place your order as soon as you are able to.
Grey Defence® GeneJOLT! Professional Strength is being given a limited release Click here if you are interested in participating.
