NAD+ is at about half the concentration in older adults that it was in their youth, thus older adults have lower sirtuin activity resulting in lower repair and more aging. The lower NAD+ levels seem not to be the result of lower NAD+ synthesis in older adults but the increased activity of CD-38 in older adults that degrades NAD+ as well as its precursor NMN. So without lowering the activity of CD-38, additional NAD+, at best would be very inefficient. Sirtuins are also turned off by natural feedback loops, as many biological pathways are by their enzymatic end products, nicotinamide in this case coming back and binding in the sirtuin enzyme. There is a specific nicotinamide binding site in sirtuin enzymes and sirtuins turn off when nicotinamide is bound in its binding site. So nicotinamide binding to the sirtuin enzyme needs to be stopped if the sirtuin enzyme activity is to be kept on. Next sirtuin enzymes have a thiol group in their enzymatic site. Thiol groups are part of proteins and enzymes that make them sensitive to the reduction/oxidation balance of the cell. When the thiol group in the sirtuin enzymatic site is oxidized the sirtuin enzymatic site does not work. So sirtuin enzymes need the cellular environment to be in a reduced state to be active.
In summary, we have listed 4 events that have to take place for the sirtuin enzymes to be active. They are:
NAD+ has to be present for sirtuin enzymes to be active; the NAD+ is used up by the reaction.
CD-38 has to be inactive. If CD-38 is active it will breakdown NAD+ and it precursor NMN.
The enzymatic end product nicotinamide cannot be allowed to bind to the sirtuin enzyme; if it binds in its designated site it will stop the sirtuin enzymatic activity.
The thiol group in the enzymatic site of the sirtuin enzyme cannot be oxidized, if it is it will render the sirtuin enzyme inactive.
Thus the sirtuin enzymes are pattern recognizing and sensing enzymes and are not activated by any singular event in the cell, they must “see” the appropriate pattern to be, and remain, active.
If it is the desire to turn on the sirtuin enzymes and keep the sirtuin enzymes on, such that one can turn on and keep on cellular repair, to get rid of cellular damage, to reverse human age these three sensing pathways and one competitor for NAD+ (there are others, but solved in the same manner) have to be considered and solutions have to be made such that the pattern sensing siruin enzymes see the cellular pattern that induces them to turn on and stay on. This is the challenge.
The concept behind the EGA® product is to override the biological switch making the evolutionary programmed choice that is preventing energy use for the biological repair of cells. That switch is the sirtuin enzymes pattern recognition system. To override evolution’s programmed choice, at the chemical level, the sirtuin enzymes have to be made to “see” the full pattern that turns them to active mode.
We present EGA® as the solution to these 4 problems:
EGA® vs the 4 problems:
EGA® provides high quality and high quantity nicotinamide mononucleotide (NMN). EGA® is a water based drink, that allows the NAD+ precursor NMN to be quickly absorbed and quickly turn into NAD+ to augment the natural, twice daily, peaks of NAD+ already in one’s body. This then is available for sirtuin use when it is needed, solving problem #1.
EGA® has a compound that turns on antioxidant defense activation, Nrf2, to increase cellular antioxidant enzymes that decrease oxidation and increase cell reduction. This cellular reduction in turn turns off CD-38 which is only active when it is under oxidizing cellular conditions. This solves problem #2.
EGA® provides a compound that increases methyl-donor SAM, for cellular methylation. This along with reducing cellular conditions provided in the above antioxidant defense activation, enables methylation, including the methylation of nicotinamide, which when methylated cannot physically fit into the nicotinamide binding site in the sirtuin enzymes because it is now too big to fit. So now the end product of the sirtuin enzymatic reaction cannot feedback to turn the sirtuin enzyme off, solving problem #3.
EGA® has, as stated in the second solution, a compound that turns on antioxidant defense activation, Nrf2, to increase cellular antioxidant enzymes that decrease oxidation and increase cell reduction. This lowering of oxidation and increasing of reduction keeps the thiol group in the sirtuin reactive site chemically reduced, therefor keeping the sirtuin active site able to do its enzymatic activity. This solve problem #4.
So EGA® theoretically solves the 4 problems that need to be solved to keep sirtuin enzymatic activity working, but does it work in practice in humans? The initial study of 12 human males from 46 to 66 years old (see study section) answers that question with a resounding yes it does. We will continue to study more individuals, especially older individuals and females. We are planning a large placebo controlled double blind study. The confirmation of this theory first with a single individual then another three then another 8 are all good positive signs for this science. See the study section for present and future studies.