A depiction of the Fountain of Youth by Lucas Cranach the Elder (1472 – 1553)

EGA® can be dissolved and drunk in water, a “Fountain of Youth”.

The scientific history of how humans got to understand their own aging

This list is kept short by only listing the key ideas, not the embellishments of these ideas, that led to successful age reversal strategies and does not include many of the paths scientists went down, and needed to go down, but have not proven fruitful to date, but may prove fruitful in the future.

History of Aging Research

The dream of a “Fountain of Youth” dates back to writings of Herodotus (Book III:23) who lived between 484–425 BC. The tale of such a fountain has been recounted across the world now for thousands of years. The Fountain of Youth is a legendary spring that supposedly restores the youth of anyone who drinks its waters. Juan Ponce de Leon, the explorer and first Governor of Puerto Rico, dreamed of this Fountain of Youth and searched for it on a 1513 exploration of what is now Florida.

In 450 BC Herodotus spoke of the longevity, physical prowess, beauty, and general youthfulness of a group he called the Macrobians. The Macrobians were a people that thrived during the first millennium B.C. Herodotus attributes no magical qualities to a fountain of youth and paints no portrait like the one of modern fantasy. He suggests, rather, that given their strength and longevity, the Macrobians likely reaped some unique nutrition from their waters. The Macrobians most likely lived in the vicinity of the Rift Valley of what is now Ethiopia.

This idea was important and not ill-founded because:  Let’s take a minute to defend Herodotus’ writings of observations from a long time ago that are often ridiculed and thought of as fanciful. The rift valley of Ethiopia (where the fountain of youth was supposedly located) at that time may well have had a number of the characteristics we now know to correlate with the health, beauty, and longevity reported. Included in this list are: Hunter gatherers in this arid region, even today, may well be eating only a single meal every other day, thus 1) a calorie restriction diet to turn on Sirtuin enzyme repair systems. These people also lived at a higher elevation so 2) lower O2 levels would lead to stable HIF-1, which can increase life and health. The volcanic activities of the area would likely mean 3) having H2S in the water to turn on Nrf2 which turns on antioxidant defense systems which leads to a longer and healthier life. 4) These same waters, if a hot spring, could provide a heat shock which turns on heat shock proteins which turns on cellular repair. If managed correctly, so the repair is greater than the damage, this can lead to age reversal (cold shock leads to the same effect) 5) Humans in smaller groups have less viral attacks leading to more symmetry / beauty. These five reasons could easily describe the observations Herodotus noted. Having, myself, visited the San people in the Kalahari desert of Africa where only 2 of these five hold true and who are the most closely related tribe, living today probably to the Macrobians, I can attest to the fact that the San are a beautiful people and remarkably healthy.

In 1901

Elie Metchnikoff wrote the Metchnikoff’s Hypothesis of Aging

Ilya Ilyich Mechnikov was from a Romanian family born in the Ukraine in 1845 that studied in Germany and was known as a Russian Zoologist. He discovered macrophages (He won the Nobel Prize in 1908 for this), they are the part of your innate immune system that eats invading organisms, and so he saw cell-mediated immunity in action and was able to realize that this was the battle of life and it led to death (are you eating it or is it eating you?) and from this he postulated aging was due to the one’s immune system’s battle (using inflammation) against toxic bacteria in one’s own gut. I would like to point out that there was a lot of incite in Elie’s choosing the gut to focus on. The gut is a key barrier between the outside world and the inside of an individual. Although you might think life ends when your heart stops beating or your brain cells stop signaling, biologists think a better definition in primitive to complex animal species is to look at when the gut lining gives up the fight of keeping the outside out. These gut cells usually die in unison, as seen in flat worm death. For an immunologist this location is important as well since biologists now think that the reason vertebrates have a newer additional immune system, called the adaptive immune system, when invertebrates do just fine with only the old, innate, immune system is so vertebrates could make friends (not attack) with some microbes in their microbiome in their gut; so these microbes could help the vertebrates get energy from the environment. As you’ll see in the following writings, that energy (if you get it and how you use it) is central to evolutionary selection and survival. That’s the key reason humans got a larger brain, to help us with this energy input / output planning in our more complex world. It is deadly to run out. Many friends and foes living in your gut lining have learned, via evolution, how to send direct messages to your brain on what they want, and it may not be exactly what is best for you.

In 1908

Max Rubner wrote the Rate of Living Theory of Aging

This idea was important because: Max saw that smaller animals usually lived a shorter life span than larger animals. They are really living more life per unit of time. Their mitochondria are producing more energy from increased use of oxygen per unit of time thus they are getting the same oxygen use per cell per lifetime than a larger animal is getting but they are using that oxygen faster. You’ll see in other writing that with age your mitochondria make less energy, slowing down the things your nerve cells do, giving you the illusion that your life is speeding up and time is going faster. You are actually seeing fewer frames per second in your brain as measured by theta waves in EEG (2D) or MEG (3D).

In 1928

Raymond Pearl updated the Rate of Living Theory of Aging

This idea was important because: Raymond did an experiment showing slowing metabolism elongated life. This made the connection between metabolism and life span and aging and later was made into a scaling exponent, between 0.2 and .33 connecting lifespan and metabolic rate. There are some exceptions to this rule like 1) bats vs rats and 2) a species living on an offshore island vs the same species living on the mainland. These examples, that do not fit the basic Rate-of-Living-Theory-of-Aging rule, show there are evolutionary reasons for these size / metabolism effects. The easier your life, the less energy you have to spend to live.

In 1935

Clive Mc Cay first observed calorie restriction elongating life.

This idea was important because: Clive, a Professor at Cornell University, showed that if you lowered calorie intake (effecting metabolism as in the prior experiments) you elongated life in multiple species. This still is the only basic underlying concept that has led to age reversal in every species it has been tried in. But do not be fooled, in its raw form, it is probably not for most humans; since the amount of food you’ll have to eat is 2/3 of the food you want to eat. A woman’s reproductive cycle stops, men’s desire for sex stops and your life is really then all about getting food and your world looks to your subconscious (for at least 3 to 6 months before your brain re-normalizes to this being seen as normal) as it is getting worse so you’ll have a negative emotional effect. The joke here is that: “is your life longer or does it just seem longer?”

In 1956

Denham Harman proposed the “free-radical theory of aging”. This idea was thought of in what was known at the time as the atomic age, and the atomic bomb was in everyone’s mind and the energy from the bomb had created damage.

This idea was important because: A free-radical is any atom that has a single unpaired electron in its outer shell of electrons. Free radical damage is associated with damage to biological molecules involving this atom in cells. Basically the electron from one molecule, which is energy, is poorly controlled by that molecule, so the electron can wonder away from that molecule to another. These electron changes, if they cannot be handle be well, destroy some molecules, which then need to be repaired or taken away and destroyed by the cell. NAD (the name given to both of the two forms, NAD+ and NADH) is involved in this electron exchange: it is called a reducing agent when NAD is in the form of NADH and an oxidizing agent when it is in the form of NAD+ (the + means it wants a – electron). NAD carries electrons from one reaction to another. NAD+ accepts electrons from molecules and NADH donates electrons to molecules. The transfer of electron is in essence the transfer of energy. Prior to understanding NAD’s role in cellular signaling (with Sirtuins) this is what NAD was known to do in its role in metabolism (cellular energy production).

In 1959

Leo Szilard wrote The Somatic Mutation Theory of Aging

This idea was important because: Leo was a nuclear chemist / physicist involved with the nuclear ideas of his time. The Second Law of Thermodynamics was seen as a central concept where order goes in a one way trip to disorder. So this electron, from the above theory, losing “order” leads to greater disorder and life could only take so much disorder. Leo saw that when things get damaged and they are not repair then problems arise, and that this was aging. Of note here is that the Second Law of Thermodynamics only holds for a closed system. Humans are not a closed system, they eat food with energy and structure and poop out the remains of that food that has lower energy and structure and are able to use that differential to make energy and structure in themselves. Thus animals can have structure for ever as long as the inflow of energy and structure is greater than their use of it and what remains in excrement. Proving this point is the fact that asexual animals (example-sea anemones) can live forever.

In 1967

Boris Vanyushin showed that DNA (of salmon) loses methylation with age (of rats 1973, of cows 1978). He also showed DNA methylation was tissue (cell) and species specific.

This idea was important because: DNA was known to carry the knowledge of life, by this time. When Boris showed that DNA changes through life, losing methylation on average as a species aged it was immediately important, especially since it was later shown to be cell and species specific, but was this methylation change a result or a cause of aging? This concept of methylation of DNA (also proteins like histones and RNA) is now the underpinnings of the field of epigenetics, differentiation of cells in development, as well as senescence of cells. When you use a differentiated cell to clone a sheep (Media star-Dolly) or polo pony (like those used by the world’s highest rated player in Argentina) you need to reverse this process of methylation to take the cell back to its undifferentiated state so it can start a new individual from scratch. Methylation, at the stage of puberty in sexual animals, is likely (research results of this in lower animals) the cause of the turning off of energy to repair cellular damage (to the level it is done in pre-puberty) that causes aging in somatic cells. There are ways, presently known, to find each of these methylation sites and reverse this methylation (process) in a specific manner at each methylation change site, that has to do with (energy conservation tradeoffs) aging.

In 1972

Deham Harman proposed that free-radicals also called reactive oxygen species (ROS) from mitochondria were the primary cause of aging.
(Free-Radical Story of Aging)

This idea was important because: The mitochondria (the organelles in the cell where most cellular energy is made) is the location where most oxidation comes from, so this again focused biologists on the site of energy production /metabolism and this also correlated his prior Free-Radical Theory and the Rate of Living Theory to the Calorie Restriction Theory. Energy in Mitochondria is made by creating an electron gradient between two sides of a membrane. This differential of electrons is like a battery. Denham retired in 1986, but was really still working in the early 1990s when I first spoke with him by telephone; he died at 98 years old.

In 1986

Richard Weindruch confirmed aging could be slowed by using calorie restriction in mice. Eating 2/3 the calories of a normal diet allowed mice to live 40% longer.
(Calorie Restriction Story of Aging)

This idea was important because: Richard, a Professor at the University of Wisconsin, showed that the calorie restriction theory held in mice, a mammal like us. He later went on to show it worked in monkeys (even closer to us) as well. This experiment was originally questioned after a subsequent experiment with monkeys by the NIH, Department of Aging. The study result differences have now been worked out and have been shown to be due to experimental design differences, and Richard’s original experimental results in monkeys are seen now to be correct.

In 1991

Tom Kirkwood and Michael Rose wrote the Disposable Soma Theory of Aging

This idea was important because: Tom and Michael brought evolution into a place of more prominence in this theory of aging, reasoning that somatic cells were not passed on to progeny in evolution and thus did not need to be maintained in as pristine a condition as germ line cells. So an organism could save energy by not spending as much energy defending and repairing somatic cells, thus use it, if they had it, for other purposes, like getting a mate or growing up children so they in turn can have children. The theory incorporated that Evolution was trading off energy use to optimize an individual’s chances to survive and have viable offspring that in turn could have offspring of their own. This also implied that energy was a key limiting factor in evolution.

In 1998

Boris Vanyushin, a Professor at Moscow State University, showed that an antioxidant (BHT) induced de novo DNA methylating enzymes, stimulated transcription of p53, and modulated DNA methylation in rats.
(Methylation and Free-Radical Story of Aging)

This idea was important: I met Boris in the early 90s when I was working with a group of the world’s experts in oxidation / reduction, Boris had already, by then, done experiments showing methylation was correlated to oxidation / reduction. This work by him connected these two important theories of aging.

In 2000

Leonard Guarente realized sirtuins were nutrient sensors and they might mediate the effects of calorie restriction.
(Calorie Restriction Story of Aging)

This idea was important because: Lenny showed that calorie restriction did not work to elongate life and promote health without Sirtuin enzymes. This allowed the only-demonstrated-way-to-reverse-age, calorie restriction, to be made into a molecular biology problem, since the key enzyme of the system was now known. It should be noted that several of Lenny’s students took up the work to solve the aging problem as well and have had, see below, significant results. None of this would probably have happen without the financial support of Paul Glenn from Santa Barbara, California; who decided at a young age to use his money to fight aging and who financed Lenny’s work. Now in his 90s Paul is personally facing the ravages of age.

In 2000

Shin-Ichiro Imai showed sirtuins were NAD-dependent deacetylases.
(Calorie Restriction Story of Aging)

This idea was important: a student of Lenny’s, Shin, now a Professor at Washington University’s Medical School, showed that Sirtuins need NAD+ to work. Without NAD+ they are turned off and this is an increasing a problem with age. NAD+ was shown to decrease with age. This lack of NAD+ in the aged describes a problem that needs a solution if age reversal is to occur.

In 2002

Kevin Bitterman showed nicotinamide inhibited Sirtuins in a noncompetitive manner with NAD+.
(Calorie Restriction Story of Aging)

This idea was important: Kevin showed that a classic feedback loop was involved with turning off Sirtuin enzymes. This happened when the byproduct (nicotinamide) of the Sirtuin reaction, that uses NAD+ and turns it into nicotinamide, binds to the Sirtuin enzyme at its own binding site, thereby changing the Sirtuin’s shape thus turning the Sirtuin enzyme off. When the Sirtuin enzyme is off there is no repair and there is aging. This describes a problem (the stopping of Sirtuin activity) that needs a solution for age reversal is to occur.

In 2007

Claudio Franceschi wrote the Inflammaging Theory of Aging.

This idea was important: For those of you paying close attention, Elie Metchnikoff, essentially stated this idea more than a hundred years prior to this theory, but now the introduction of molecular biology had happened and this theory could be restated in modern terminology and with modern demonstrations. This Theory noted that basal levels of inflammation were increasing with age. Several studies (Arai Y 2015, Varadhan R 2014, Lee JK 2012, Derhovanessian E 2010, Wassel CL 2010, Reuben DB 2002, and Taaffee DR 2000) have shown that inflammation markers, such as Interleukin-6, were predictive of all-cause mortality. The basal levels of inflammation markers like IL-6 and TNF-α [when not reacting to a short term need to be activated] appear from these types of human studies to be the best blood predictors of future death that medical diagnostics presently has. Separate studies have shown the correlation and predictive value of these inflammation markers to the individual disease of aging as well. Of note here is that drugs like the popular Humira insert monoclonal antibodies (in this case to the TNF-α pathway) to inflammation pathways to prevent their use, which is good when you do not need these pathways but quite bad when you do.

In 2008

Katheryn Ramsey and Katheryn Mills showed nicotinamide mononucleotide (NMN) produced age reversal effects in mice.
(Calorie Restriction Story of Aging)

This idea was important because: NMN is a precursor of NAD+. The making of NAD+ is highly regulated and NMN is in the synthesis pathway of NAD+ after the main regulatory enzyme to make NAD+. Adding NMN to a cell gets past the main regulation of making NAD+. Also NAD+ is too big to get through the gut lining of a mouse or human and so giving NMN in drinking water (if and when it is taken up by the gut, and then later via a somewhat unknown travel pathway turned into NAD+) gets by this problem. This is the first study in mammals that shows changing NAD+ levels changes outcome. So the chain of ideas through time took us from lowering metabolism (1908) to lowering calories (1935) to increasing Sirtuin enzyme activity (2000) to increasing NAD+ (2000) to increasing the NAD+ precursor NMN (2008) to get age reversal from 100 years of optimizing a single concept. Still to come, though, is the need to keep the Sirtuin feedback loops off, which will bring in the others that where understanding oxidation / reduction pathways, methylation pathways and finally the constructing a total synthesis of all these ideas to form a solution to biological aging.

In 2009

Brock Christensen showed DNA methylation was decreased outside CpG islands and DNA methylation increased inside CpG islands with age in humans.
(Methylation Story of Aging)

This idea was important because: Brock put more precision into the Methylation Theory of Aging proposed by Boris previously. Later this knowledge was made into a “biological clock” by Steve Horvath at UCLA to measure biological age (how much your body had deteriorated and progressed towards death) instead of chronological age. A New Zealand study showed the rate of biological age progression can be up to a 3X differential between individuals in humans.

In 2010

Gaelle Laurent wrote the Retrotransposon Theory of Aging

This idea was important because: This is really another remake of the Elie Metchnikoff / inflammation theory. In this twist, the inflammation is due to fighting genetic elements left over from the approximately 50 invasions our ancestors had from retro viruses (HIV like viruses). Evolution has used many techniques to keep these viruses, which have integrated into us (about 45% of our total DNA of which 8% of our total DNA still looks like intact retroviruses), under control, we have even used some retrovirus elements for our own benefit, but the battle to control these “jumping genes” continues to this day. One way to keep them under control is to methylate the incorporated viral DNA so it is not used. But as we’ve seen methylation decrease with age and some of these viruses then start getting expressed, thus the Theory. Other endogenous viruses can also be included here, especially the herpes family of viruses, and especially the Cytomegalovirus (CMV) in that family, a lot of the immune system is taken up just fighting CMV in old age if you have it. Alzheimer’s disease (a disease of aging) research shows the activation and amplification of these endogenous viral genetic elements in the diseased brain tissue cells affiliated with Alzheimer’s disease.

In 2011

Jun Yoshino and Katheryn Mills showed the benefits of nicotinamide mononucleotide (NMN) was getting past the rate limiting enzyme in mammalian NAD+ biosynthesis called nicotinamide phosphoribosyltransferase (NAMPT) and that NMN is converted into NAD+ efficiently in mice.

This idea was important because: Jun and Katheryn showed why NMN was working to turn on Sirtuin enzymes. After this highly regulated step by NAMPT, NMN is converted into NAD+ in each cell’s nucleus, cytoplasm, and mitochondria by a set of 3 enzymes called mononucleotide adenylyl transferases (MNMAT 1,2,3), each specializing in these locations.

In 2012

Leonidas Chouliaras showed calorie restriction prevents the age-related changes of methylation of DNA in mice.
(Calorie Restriction and Methylation Story of Aging)

This idea was important because: Leonidas connected the Calorie Restriction theory of McCay (explained by the Sirtuin Theory of Guarente and then by the NAD+ Theory of Imai) to the Methylation Theory of Aging of Vanyushin.

In 2012

Hassina Massudi found a link between oxidative stress from ROS, aging and a decline in NAD+ levels in human tissue.
(Free-Radical Story of Aging)

This idea was important because: This is important because Hassina confirmed the connection of the Free Radical Theory to the Calorie Restriction Theory that, as seen above, was going to the Sirtuin Theory of Aging by Guarente and then to the NAD+ Theory of Aging by Imai.

In 2012

Rajindar Sohal wrote the Redox Stress Hypothesis of Aging.
(Free-Radical Story of Aging)

This idea was important because: Rajindar updated the Free Radical Theory to present understanding of the cell’s use of oxidation as well as reduction. Both oxidation and reduction are important to the cell. Most importantly low levels of oxidation (mostly by hydrogen peroxide, the breakdown intermediate product of the more toxic oxidants in the cell) is assessed by the cell and then used to turn on Nrf2 which then in turn, turns on the cells antioxidant enzymes which then lead to overall reduction in the cell.

In 2013

Kathrin Schmeisser and Johannes Mansfeld showed sirtuin lifespan extension depends on methylation of nicotinamide by amine N-methyltransferase (ANMT) making 1-methylnicotinamide to prevent nicotinamide’s inhibition of Sirtuins. Nicotinamide decreases life span at high dosage.

This idea was important because: Katherine and Johannes showed, in this experiment, the solution to the problem, stated above, that the nicotinamide (made as a byproduct in the Sirtuin reactions) stops the Sirtuin enzymes thus leading to aging. The solution is to methylate the nicotinamide byproduct, thus keeping Sirtuin enzymes turned on, which is done in nature by the method they described.

In 2013

the reversal of age in mice was scientifically confirmed in a publication of the scientific journal Cell by lead author Ana Gomes working in David Sinclair’s laboratory at Harvard Medical School. This research used nicotinamide mononucleotide (NMN) to reverse aging in mice.

This idea was important because: Ana not only confirmed the results previously described from Imai’s lab personnel but showed the problems arose when the mitochondria (which is an evolutionary add on to eukaryotic cells and one of the main reasons for the innate immune system being what it is) was not “communicating” with the nucleus on the cell where a lot of its DNA had migrated. Probably more important for the field of aging research was the fact that David Sinclair with his Harvard Medical School Professor credentials went to the lay press and declared to the world that age reversal was real and could be applied to humans. I for one heard this “communication” and started to research the field full time. The connections of researchers to this include Anna a student of David’s who in turn was a Post-Doctoral fellow along with Shin Imai (his students include Jun Yoshino, Katheryn Ramsey and Katheryn Mills) under Lenny Guarente who were all financed to some degree by Paul Glenn.

In 2014

Egaceutical Corporation was founded to bring nicotinamide mononucleotide (NMN) to the market place for human use.

This was important: NMN at the time was $2000 per gram and the world’s supply of NMN manufacturing was only able to provide NMN for a hand full of humans at the amounts they would need if this was to be used for age reversal. The initial idea for a company was just to supply the future need of this singular compound.

In 2014

Egaceutical Corporation started a study using EGA® for human age reversal. EGA® is a water based product that includes three ingredients: nicotinamide mononucleotide (NMN) a compound that turns into cellular NAD+, a compound that increases methyl donor, SAM, for cellular methylation, and a compound that turns on antioxidant defense activation, Nrf2, to increase cellular antioxidant enzymes that decrease oxidation and increase cell reduction.

NMN had only, at the time, been used in mice. Somebody needed to try it in humans for the first time. I took on this challenge, first with one person, myself, with massive diagnostic testing every month. It was only after starting this study, on myself, that I learned that increasing NAD+ (via NMN) by itself was not the answer to human age reversal and that I could get a patent on the solution /discovery that allows for age reversal that I came up with after the realization that the singular NMN was not the solution. The Egaceutical corporation goals were now redirected, after this realization occurred, to monetize the newly conceived solution to the age old problem of old age. Prior to this EGA® product, it was thought that the singular compound, NMN, that gets made into NAD+ , would reverse age as it had been reported, by Harvard Medical School to the lay press, to do, in mice, after a week of NMN and had been extrapolated, by this demonstration, to work in humans. I started out on 7 grams of NMN a day (2 X 3.5 gram doses 12 hours apart) for the initial three months of the study, using the (low side of a) normal dose equivalence used by the pharmaceutical industry to ratio the mouse dose used by Harvard to a human dose. After getting an initial positive outcome / results, the results diminished with time forcing a total reanalysis of the study protocol. A closer look at the Sirtuin enzyme’s biochemistry showed feedback loops were most likely turning the Sirtuin enzymatic activity off. To turn the Sirtuin enzyme activity back on and keep it on the feedback loops had to be stopped / turned off. This is where the control of the extra two cellular pathways comes in. Controlling the methylation pathway via turning on SAM, which in turn needs the turning on of the antioxidant defense system pathway would control the feedback of nicotinamide to the Sirtuin enzyme. The turning on of the antioxidant defense system via turning on Nrf2 would also keep the thiol group (which proteins /enzymes use to measure the oxidation / reduction balance in their environment) in the reactive site of Sirtuin enzymes, with its sulfur atom, reduced; which would allow the reactive site of Sirtuins to stay active. Reduction from the turning on of Nrf2 would also keep the CD-38 enzyme turned off so it did not eat NAD+ and NMN before they could be used by the Sirtuin enzymes. This EGA® product with three compounds / parts then needed to be tested to show all three parts were needed, and that two out of three pieces were not good enough. This took another 6 months to show.

In 2015

Xiao-Hong Zhu showed you can measure NAD non-invasively in the live human brain with an MRI machine (using P31) and that NAD quantity is lower in older humans than younger humans.

This result was important because: Measurement is what science is all about. Having the ability to measure NAD in humans in real time without any negative effects allow the ability to monitor treatments that aim to raise NAD levels in older individuals to turn on Sirtuin enzymes to reverse age.

In 2015

other human males showed measurable age reversal results using the EGA formulation

These results were important because: Once I had shown a positive result in myself, others that had followed my progress, wanted to try the formula on themselves. Three others males, that had been waiting to start for a year, started. When they were sufficiently along with all positive and some quantifiable diagnostic results with no negative results, ten others, all males, which had also waited over a year to start, started. These males were all willing to share their diagnostic results and experiences with me and they were all very positive as well, with some quantifiable results and again no negative results. I knew from previous studies, that male mice were reacting slightly differently than female mice. All individuals to start with were initially human males. Next to start on the formula was the first human woman; again she got very positive results and no negative results. A more formal, University Medical School, independent, placebo controlled, blinded study is being planned, the key ingredient to start this study is the $20 million minimum cost.

In 2015

Egaceutical Corporation filed the first patent application for human age reversal. The patent application was to protect Egaceutical’s product now trademarked EGA® (age spelled backwards).

This invention was important because:

    • Egaceutical’s patent provided a “Unified Theory of Aging” which conceptually unified the 10 previous described Theories of Aging which include:
      1. Metchnikoff’s Hypothesis of Aging (Metchnikoff E 1901)
      2. Rate of Living Theory of Aging (Rubner M 1908, Pearl R 1928)
      3. The Calorie Restriction Theory of Aging (McCay C 1935)
      4. The Free Radical Theory of Aging (Harmon D 1956)
      5. The Somatic Mutation Theory of Aging (Szilard L 1959)
      6. The Methylation Theory of Aging (Vanyushin B 1967)
      7. Disposable Soma Theory of Aging (Kirkwood T and Rose M 1991)
      8. Inflammaging Theory of Aging (Franceschi C 2007)
      9. Retrotransposon Theory of Aging (Laurent G 2010)
      10. Redox Stress Hypothesis of Aging (Sohal R 2012)

Some of these theories had been connected to other of these theories over the years as described above. They had never, though, all been all connected together and more importantly:

B. No one had made this combination of ideas (or any ideas) into a physical solution to reverse human age and then shown the idea in a real human example to measurably reverse human age and measurably reverse a disease of human aging (arthritis) that results predominantly from the progression of age.

In 2016

Juliana Camacho-Pereira showed CD-38 activity goes up with age and this causes the decline of NAD+ with age.

This idea was important because: Juliana put a new spin on the cause of the decrease of Sirtuin activity with age. Yes, NAD+ was needed for Sirtuin activity and yes, NAD+ was going down with age, but the reason NAD+ was going down with age is because CD-38 was breaking it apart before it could be used by Sirtuins. A therapy to reverse age now needed not just to increase NAD+ as one ages but to turn down or off the breakdown of NAD+ by CD-38. EGA® was working because it turned up reduction in cells which turned off CD-38 which only works under oxidation. This is also a correlation for a mechanism of why the Free-Radical theory, now the Oxidative Stress Theory of Aging is an important contribution. Other molecules like Apigenin and Quercetin, that turn on Nrf2, which in turn, turns on antioxidant enzymes genes like SOD, inhibit CD-38 most likely with the reducing effect they create.

In 2017

the PCT published the first patent application for age reversal in humans, PCT/US2016/055173, called “RESETTING BIOLOGICAL PATHWAYS FOR DEFENDING AGAINST AND REPAIRING DETERIORATION FROM HUMAN AGING”. The inventor is Joel T. Huizenga of Egaceutical Corporation.

Integration of the original lines of aging research into the “Unified Theory of Aging” to unify all ten theories of aging described in this timeline.

This was important because: Patents on novel ideas that can be made into physically useful products for humans (inventions) allow for the monetization of that idea due to the ability it gives to take on investors whose money can then develop the ideas into fully developed and tested products for a market place, and thus be able to give back, to the investor, a larger than normal financial (a return without a monopoly) return on their investment. Patents also allow the public to see ideas that otherwise would be held secret as trade secrets. Since the patent is being sought in Australia, Brazil, Canada, China, Europe, India, Israel, Japan, Korea, Malaysia, Mexico, Russia, Saudi Arabia, Singapore and The United States; it will be available in many languages as well.

Timeline Of Advancements In Age Reversal

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