We are looking for both healthier lives which is referred to as health span and longer lives which is referred to as life span. These two really go together and it is thought that you cannot separate them, although many scientific researchers think it is politically beneficial to promote health span and not to mention lifespan as the benefit of these therapies. Researchers, needing to seek more money for their research, see a benefit in mentioning that aging research probably has a better cost / benefit ratio since it addresses multiple diseases with one therapy and gets to the basic fundamentals of disease progression.

Yes, a surrogate marker for biological age is needed that tells you if there is a change, the direction of change, and the rate of change of biological age. Thankfully there are probably at least 10 surrogate markers that are good although none are perfect.

The 10 most promising biological clocks to date are:

1) The Inflammaging clock by Arai

Included are 4 tests, IL-6, TNF-α, CRP, and IgG for CMV

2) The Methylation clock by Lavine and Horvath

called the PhenoAge clock

3) The Transcription clock by Peters or the one by Fleischer

4) The Proteome clock by Enroth

5) The Microbiome clock by Galkin

6) The Structural Brain clock measured with MR by Cole

7) The Slow Wave Non-REM sleep clock by Mander

8) Telomere length by Blackburn

9) Nucleolar size by Tiku

10) NAD+ quantity in brain measured with P31 MR by Zhu

Yes, there are, they include:

1) The getting off the floor test

The lower the number of touches you use to get up, the younger you are

2) The static balance test

Older individuals have less balance

3) The skin elasticity test

If you pull your skin, younger skin regains it shape faster

4) The catching the ruler test

If someone else drops a ruler in your semi closed hand, you see the measurement on the ruler of where your hand catches it, this measures how fast your reaction time is.

5) The Lung function test

You see how faraway you can blow out a match or candle

And I think the “deep learning” analysis of a photo of one’s face for biological age will be on the internet soon. Reports seem to say it is quite good. The areas around the eyes are most telling.

The best presently, I believe is the grouping of inflammation markers because these have been shown to be predictive of how long one will live by six human long term studies, they have also been shown to be predictive of if one will individually get one of the major disease of aging. One has to remember to only take these inflammation tests when your immune system is not activated, since one wants to get a measure of your immune system baseline. The baseline is your immune system’s level when it is not active and this baseline level creeps up with biological age.

These include:

1) Drugs that are already approved by the FDA and that are on the market for other medical reasons

2) Drugs that are non-natural and presently being developed by pharmaceutical companies

3) Drugs that need FDA clearance but are compounds or grouping of compounds that are already in humans

4) Drugs classified as Food by the FDA but are also made in humans

5) Drugs classified as Food by the FDA that are made in plants but not in humans

6) Lifestyle therapy approaches to human age reversal

The dream for a solution that is only a single molecule comes from several directions:

1) The first, of course, is that the biology of humans, really all animals, is fundamentally based on the conservation of one’s energy unless there is high probability of excess energy returned from any energy expended. So taking a single pill that takes no energy to take is an easy sell to the masses that seek to expend as little time and energy as possible on any therapy.

2) Secondly the selling company wants a compound that can make as much money for as little effort as possible and a patented compound can make this happen. This is the only way to get more than, what is called in finance, a market rate of financial return. One can only get a patent on a single therapeutic molecule if it is non-natural so pharmaceuticals are in the business of making and selling non-natural compounds even though the probability of good effects from these drugs are extremely low and the probability of negative effects from these is very high compared to a molecule the human body already has experience with in evolution and has evolved to use effectively. Pharmaceutical companies often try to find these natural “in body molecules” and then change them to a non-natural compound to be able to get a patent on them, but changing these natural compounds usually always brings with it negative effects, and the positive effects are quite often lost or diminished. This is the process that is happening in the age reversal field presently.

3) Thirdly a single molecule, as opposed to a grouping of molecules is exponentially easier, quicker and cheaper to get past the regulatory laws of the world so almost every pharmaceutical therapy is a single molecule, even though human biology has very complex regulatory mechanisms such that a single molecule regulation of anything in the body is probably non-existent.

4) Lastly, any life style changes that are recommended by an expert are usually very energy consuming to carry out for an individual so are not embraced by customers and for the person selling the idea, very hard to get paid for and so are not energy efficient for any individuals to develop, market, or sell.

So diet, exercise, and other life style changes usually lose out to energy saving life styles like sitting on the couch which does not exercise you physically, and watching TV which does not exercise you mentally, while eating high calorie foods which is the opposite of a beneficial calorie restriction therapy. These human tendencies are all in direct opposition to what is needed for health and longevity of humans.

Two important considerations for a therapy for age reversal are:

1) The timing of everything in the therapy needs to be correlated with everything else in the therapy and to one’s biological clock which is also called circadian rhythm.

2) The quantity of everything in the therapy needs to be at the right quantity and correlated with the quantity of everything else in the therapy.  These two considerations are often overlooked.

NAD+ is a molecule that is already found in the body but declines by half in older age. It is given in an IV, since it does not get in through the gut. An exception to this lack of gut absorption may be in babies since NAD+ and its precursors NMN and NR are all found in human mother’s milk. Mother’s appear to be able to change the concentration of these ingredients, apparently hourly, according to the baby’s needs, or maybe it is the mother’s need too sync the baby’s clock to hers. With IV NAD+, one has to sit for 8 hours a day for 8 to 12 days. This has been used in about 1000 patients for drug and alcohol addiction, although no scientific trials have been reported on this use. One can only give NAD+ as a very slow IV drip since quicker IV rates lead to a significant side effect but that side effect is quickly reversed when one slows the rate down. Patients for this NAD+ use that I have spoken to, seem to give this NAD+ IV therapy positive approval, although very little science has been done on NAD+ IV therapy in humans.

Rapamycin was found in a bacterium on Easter Island which is called Rapa Nui by its natives. The island is known for its Noai statues. Rapamycin is a transplant rejection drug that suppresses the immune system. This is the one in six successful age reversal drugs shown in mice that work better in females. Presently there is a trial using dogs at the University of Washington with rapamycin. Rapamycin’s side effects are thought to be far too great for use in humans so variants without the side effects of this drug are being made for humans.

Dasatinib is a drug used in chemotherapy for leukemia. It was first used as an age reversal drug by Mayo Clinic researchers in mice. This “senolytic” drug along with Quercetin a polyphenol, which is a food based compound, gave beneficial results in mice. A 14 patient human pilot study using these two compounds for idiopathic pulmonary fibrosis, which is a fatal disease with no known cure, seemed to have promise. A larger study was deemed warrented.

Metformin is an off patent diabetes drug that has been used by a lot of people for a long time. In analyzing the results from these diabetes patients it was observed that many of the diabetes patients with metformin had better health results than not only the diabetic patients that had not taken this drug but also better than non-diabetics.  So a clinic trial for humans has been designed at a cost of $69 million and presented to the FDA to use Metformin as an age reversal drug. The money to do this trial has not been raised yet though.  Since metformin is an off patent drug and no one can make a large profit from its sale, the studies main proponents are really looking for a path through FDA for their own companies’ age reversal drugs which they can make a large profit from. Metformin’s probable biological mechanism of action was shown in fruit fly studies to be dependent on an increase in gut hydrogen peroxide. This hydrogen peroxide increases Nrf2 which then increase the anti-oxidant defense system enzymes.

Many of these drugs are improvements of known drugs, either as better drugs or as financial return improvements due to being patentable.

In an offshoot of NAD+ therapy, Calico, an Alphabet company (better known to the public as a Google company) was started with $1.5 billion in 2013 with an activator of an enzyme called NAMPT that makes NMN which is a precursor of NAD+. They also refer to this therapy as a Sirtuin activator, since NAD+ activates Sirtuins which start cellular repair. They purchased this therapy from the University of Texas. This drug will still need the two other types of compounds and need use of the Egaceutical Corporation’s EGA® patent.

In this category, as well, are inhibitor drugs to an enzyme called CD-38 that breaks down NAD+ and NMN. CD-38 increases in older people and is now thought to be the reason NAD+ decreases as one ages. Initially nutraceuticals were found in this category. Now these are being altered so patents can be gained to make profitable pharmaceuticals. CD-38 is turned off with cellular reduction which is gained from the turning on of Nrf2 which turns on the cell’s anti-oxidant enzymes. EGA® controls CD-38 by turning on cellular reduction by turning on Nrf2.

With a manipulation of rapamycin, drugs are being made that inhibit mTORC1 but do not inhibit mTORC2. Non-specific rapamycin inhibits both.  It is thought that this mTORC2 inhibition is what causes rapamycin’s bad side effects.

Senolytic drugs preferentially kill senescent cells, which are damaged older cells that have stopped dividing and that spew out toxic compounds like immune modulators that hurt neighboring cells. Egaceutical’s EGA® lowers these immune compounds. These senescent cells are made in research settings by irradiating cells. Radiation is a form of oxidation. Then these oxidized cells are given senolytic therapies which are often polyphenol compounds that turn on Nrf2 that then turns on anti-oxidant defense systems. So in essence adding antioxidant enzymes to oxidized cells solves the “Senescent cell” problem. Leading some to ask “Is senolytics just a rebranding of the older RedOx theories of aging?”

Anti-oxidants use was discontinued in the medical field when small molecule anti-oxidants where shown to be ineffective in large heart disease human trials. The reason for this was that small molecule anti-oxidants once they are oxidized by oxidants cannot be effectively re-reduced, in other words recycled, and then they are effectively oxidants with a negative cellular effect. With polyphenols that turn on Nrf2 and thus antioxidant enzymes, there is no need to rejuvenate, so this problem is solved. More is known now about cell biology than was known during those times 20 to 30 years ago, so maybe a rebranding of RedOx to senolytics is good to get those problems behind us.

The problem with this senolytic approach is not the concept but the specificity of the drugs being used presently. One example of this is the lead compound from Unity Biotechnology that kills 20% of senescent cells but also kills 5% of good cells. The therapy was used for arthritic knees in mice. Bad cells are only 1% to maybe 3% of the amount of good cells, so in real number of cells (.01 X .2=) 0.2 %  bad cells were killed and (.05 X .99=) 5% good cells killed. This makes the kill ratio (.2%/5%), meaning that only 4% of cells that were killed were bad cells. This drug was the main value in the company’s IPO which sold for a large valuation. A human phase I study was announced in June of 2019 to check for the drug’s safety.

Mitochondria is where cellular energy is made and older people have less energy, so mitochondrial drugs are being developed that consist of peptides made by mitochondria that are then changed so the company (Cohbar in this case) could get a patent for financial protection and profit.

Stem cells can be seen as a part of repair therapy. Stem cells themselves do age, so stem cell therapy is not truly an age reversal therapy. They are a tissue repair therapy though. Stem cells are cells that are undifferentiated so they can still divide into the type of cells you need at a site of injury or a site that needs cell replacement. Cell replacement happens when it is more energy efficient than cell repair, or when repair is not possible because the needed cells are just not present. An example of this is in male pattern baldness where the hair follicle dies and is therefore not present to repair. In biology your body decides whether to repair a cell or have the cell die under controlled circumstances, call apoptosis, and then to replace the cell with a new cell made from a stem cell.

The use of stem cells for repair is great in theory but has had significant problems to date. Although working in research, stem cell therapies are not working commercially yet and are mainly sold to get a placebo effect. Technically the complexity of doing stem cell therapy is still too difficult and expensive to perform for the general public. The main difficulty is getting the right live stem cells into an area where they are needed to replace damaged cells and having the stem cells turn into the needed cells and then have them integrate into the tissue and not have these new cells attacked by one’s own immune system. Sadly most stem cells are already dead by the time they reach even the operating room.

Yes, stem cells age. If and when effective stem cell technology for repair is available one will want to reverse one’s age first so you can have younger stem cells to harvest and use to grow up into a larger volume and then inject back to where cell replacement is needed.

It is possible to de-differentiate cells that are already in the correct location in the body into stem cells with the 4 transcription factors, although the physical control of this process has not been worked out yet.

Wnt technology looks promising as well. It makes a cell you have, develop into a cell that you want but do not have. This technology is being developed by company named Samumed and it should be able to solve the male baldness problem if it ever reaches the market.

The gut is an important place in aging research. On the inside of the body at this boundary is the blood stream and on the outside of this boundary is the gut microbiome. Changes in both of these complex systems that come with age have an effect on one’s biological age, and changing these systems back to their youthful state can make you younger. Although this is known, the problem with this type of therapy is that no one yet understands these systems well enough to say exactly what needs to be changed and even if one knew what needs to be changed there would be the difficulty of making the change correctly. Research in these areas will have future benefit.

Blood research started with an old technique called Parabiosis, which is the connecting of the blood supply of two individual animals usually Rats. For aging research, researcher sewed young Rats to old Rats. These studies showed that there are things in the younger rat’s blood that can make the older rat younger and things in the older Rat that can make the younger rat old. Researchers are now trying to fractionate the blood to find out what in particular these ingredients are. One ingredient in the blood are lipid vesicles, made by the hypothalamus (an organ in the brain that oversees body’s biological clock) that has the enzyme that makes NMN in them. These vesicles are marked on their membranes to go to cells that need to make more NMN. Another ingredient may be GDF11 and some people already taking this but without proper controls so no knowledge has been gained from this as yet. Individuals are injecting young people’s blood by the quart at a cost of $8,000. This is a far cry from continuous infusion of the blood of a young person and positive results have not been seen to date and are not expected by experts in the field. This is probably safer though than sewing yourself to a young person because in the Rat experiments the young rat tried to bite the head off the old rat. The FDA has now ordered a stop to young plasma being used by older individuals for age reversal.

There are four separate microbiomes, on the skin, in the first part of the digestive track, in the last part of the digestive tract and a women’s vaginal microbiome. These areas are all inhabited by very different organisms. The microbiome in the gut has some organisms that promote health and long life and other organisms that promote poor health and a shorter life. Recently antibiotics in old mice were able to kill organisms that shortened life. These organisms are not present in younger mice.

Some think that getting the microbiome of a younger person will help to make you younger. This is called a fecal transplant which sounds nicer than eating shit. In modern medicine these transplants have mainly been used to counter C. difficile infections which cause diarrhea.

The most famous fecal transplant in history was done on Hitler, prior to his rise to power. He suffered from severe digestion problems. The physician that did the transplant became Hitler’s personal doctor and was with him every day until Hitler shot himself in the bunker at the end of the war or in the revisionist history filmed for the History channel in “Hunting Hitler”, escaped to Argentina and lived out the rest of his life.

The gut microbiome is very complex and the number of different types of microbes is quite large. Exactly which organism are helpful and which are harmful and how they all interact is presently not known. It has been extremely difficult to change an individual’s microbiomes as well, although marketers seem to indicate to the public it happens in a beneficial way merely by taking their product. Experts in the field strongly disagree with these advertisements although believe that in the future therapies will come from more knowledge in this field.

Your gut microbiome originates from your mother’s vaginal microbiome and is nurtured with food for the correct microbiome growth coming from the mother’s milk for the baby. Once in place these bacteria are able to send messages of what they want for food to the nerve cells lining the gut that then carry these requests directly to your brain. This is why you then walk to the refrigerator and grab the specific food that you grab. To change one’s gut microbiome you would need to provide food for the microbiome bacteria you want while starving out the bacteria you do not want. This process would take several months at a minimum and the whole time these dying bad bacteria would be letting your brain know they were not happy by making you unhappy. The number of bacteria species in your gut is directly correlated to the number of different plant species that you eat regularly. Many of these plant species have ingredients like types of fiber that your cells can not digest but can be digested by specific microbiome bacteria in your gut. They then provide 2 to 4 carbon based molecules that have been shown to be beneficial to your health and life span.

One company is thinking of giving you bacterial viruses that specifically kill bad bacteria but leave good bacteria. This may be what advance civilization needs to  make our attack on invaders more specific which would back up evolution’s original reason for giving us the second immune system that we spoke of previously.

After Sirtuins were found to need the energy molecule NAD+ to be active and it was found out that the concentration of NAD+ appeared to go down by half in older people, then the search to increase NAD+ in human cells began. NAD+ itself cannot be absorbed through the human gut, so the precursor of NAD+, which is nicotinamide mononucleotide, called NMN for short, was tried and that was able to be transported through an active transport mechanism in the gut. A precursor of the NMN precursor call nicotinamide riboside, or NR for short, appears to be passively absorbed by the gut as well. The body seems to use NMN as the distribution system of the body’s NAD+. There is an extra cellular NAMPT enzyme, made in the hypothalamus of the brain, which regulates the body’s clock. This NAMPT is extruded and then carried in lipid vesicles earmarked for specific cell types in the body. There is also an intracellular NAMPT enzyme that makes NMN for inside cells in the body.

This NMN is not only made in human cells, it is made in other plant and animal cells that you eat. So it is a food and as such has special regulations as a food and not as a drug in the eyes of the FDA. Eating or drinking NMN in water gets it into the body and it is then turned into NAD+ within 15 minutes. Researchers have started using both NMN and NR in humans. NR research was started first since initially NMN was considerably more expensive. Chromadex, a commercial firm, made NR available via subcontractors to the public. NR has been sold by these subcontractors and now is sold by Chromadex itself in very low dose pills. This is so NR pills could be priced at an amount the public was already used to buying other nutraceuticals for which is around $2 dollars a day. Initial small human studies have been published on NR although none so far have results showing the positive results that one wants to see in an age reversal therapy. Of note is that there have not been any significant negative results of taking NR in journal reports so far including one article by Chromadex that was double blinded and placebo controlled.

Groups selling very low dose NMN pills have now also popped up on the internet as well, although studies on the use of NMN have not been published. A safety study for low dose NMN by Shin Imai and another safety study by David Sinclair are expected soon. Shin Imai says he is using a 125 mg dose of NMN in his human study because of the “nicotinamide problem” of NMN used in doses greater than 125 mgs.

When the NAD+ that is made from NMN is used by the Sirtuin enzymes the NAD+ is broken into Nicotinamide which then can come back and bind to the Sirtuin enzymes. When Nicotinamide binds to the Sirtuin enzymes it stops the Sirtuin enzymes from working. Nature has a way to stop this process and it is by adding a methyl group to the nicotinamide so it is then too large to bind to the Sirtuin enzyme.  There is also second feedback loop that can stop the Sirtuin enzymes that involves the oxidation of a sulfur group, called a thiol, in the Sirtuin active site. Egaceutical Corporation has used this knowledge of cell biology to formulate a natural three small molecule solution that keeps Sirtuins active with higher NAD+ concentrations.  This is the patent protecting the EGA® product.

I was the first human to use NMN. I had been interested in cellular aging my whole career in molecular biology but I got interested specifically in the use of NMN for age reversal in December of 2013 after Anna Gomes published an article on NMN use in mice in the prestigious journal Cell. I called Ana and spoke with her a while as well as with Shin-Imai who had been doing the NAD and Sirtuin studies with mice for almost 2 decades and was very impressed with their research results, not for forming a company, but for myself. I was 59 and ½ at the time and I had just heard my 92 year old father, who was a scientist of few words, say “no one tells you how awful growing old is”.

I then looked into the cost of NMN from the only company that was really selling it at the time and it cost $2,160 a gram and I figured from the mice experiments along with the normal conversion rate used to translate therapy doses from mice to men that an equivalent dose for a 200 lbs. guy like me was 4 grams of NMN twice per day. That means $17,280 a day for this therapy ingredient, and the mouse study was for a week which is about 8 months in human time scale, making the price of a single person study over $4 million. From my background in business, I knew that the price was that high just because no one was using it. So I looked in to how to make it, which is the same way nature makes it. Then I put out a bid to 30 international companies that make this type of molecule, to make NMN for me. Each of the contacted companies said they could make NMN and each stated a very reasonable price. I said great to each of the companies and told them when you make some NMN, send me a gram and I’ll test the purity to see how well you did making it. I waited, and waited, only one company was able to send me a gram, but it was of excellent quality.

I told a friend of my interest in NMN and he said he was interested too. He then asked a group of his wealthy friends if they were interested in investing into this project and they all said to talk to their investment advisor. He thought this would take too long to do, so he changed his approach on the fly and asked them if they wanted to take some NMN. They all said yes and were willing, pretty much on the spot, to open their check books and write a large check to get some NMN, at a price based on the initial price the contract manufacturer was telling me it would cost.

So with this money I sent the manufacture of the good gram of NMN $80,000 for KG amounts. I again waited. After a long wait they finally admitted they could not make NMN in KG amounts. Scaling the synthesis was a problem as it quite often is in chemistry. Luckily they sent the money back, but then there was no path forward. Before I could tell the group this bad news, I was approached by a group centered around a scientist that had studied under a noble laureate in the US that they could provide KG quantities of NMN which provided a path forward, unfortunately this NMN, which tested at 99% purity, was more expensive than what we had planned. Realizing from my past with the major pharmaceutical manufactures that normally individuals not only do not pay to test a therapy but want to be paid. I thought our project lucky to be able to move forward. When the KG amounts finally came, I did not want or see the benefit to have anyone but myself to be in the first round of tests. No one objected. I started doing tests on myself prior to taking the NMN and then repeated these every month. In all about 300 blood tests and many other physical tests were done every month. My results can be seen on the EGA patent, in its example section which is near the end of the patent. Most importantly there were no negative effects from the NMN. I erred on the lower side of the estimated dose and took 7 grams of NMN a day, this was split into 2 doses of 3.5 grams each and dissolved in ½ liter of water that I drank at 7 am and 7 pm to coincide with the known circadian rhythm changes of NAD+ seen in mice extrapolated to humans. NAD+ peaks in mice two time a day 12 hours apart with lows in-between the peaks that one wants to preserve. The object is to increase the difference between the peaks and the lows. Age flattens out this circadian rhythm leading to poorer health. The therapy needs to be taken to increase the NAD+ peaks and then have the NAD+ disappear before the lows which also have biological value.

The positive results started showing up in me about a week into the study. These results are listed in the patent example as well. Of importance was that after about month 2 to 3 the NMN effect weakened. I was worried about this since the funders of the project had not started on their dose yet. I informed them of this setback and then did a deep dive into the scientific literature again. What I found from looking at the literature on the molecular biology of the Sirtuin enzyme was that there were feedback loops that turned off the Sirtuin enzyme so that even if it had the NAD+ it would be turned off. I finally realized from past work I had done that these feedback loops could be turned off with two additional small molecules that were also naturally found in the human body’s cells and which were also available in the food supply so they would also be food based products as defined by the FDA. One of these small molecular additions to the therapy increased cellular methylation and the other increased cellular reduction via Nrf2 activation. The specific molecular biology reasoning for each of the two additional small molecules is explained in the EGA® patent. The patent is posted on the Egaceutical website for anyone seeking this information.

I added these two small molecules to my ½ liter drink of water and the beneficial effects of NMN then could not only be seen again but were enhanced. Since this problem was solved, three addition men started on this triple therapy and within a week they too started getting great results without any negative results. After a few months with these three guys an additional 8 men started on the triple therapy. All self-reported to us good outcomes without any reported negative outcomes, so I applied for a patent. The patent includes any therapy that includes molecules that control these three necessary pathways which is needed to get the positive age reversal result we were seeing. The age reversal results were measured using the inflammation testing I talked about at the beginning of this segment.

My understanding was that this therapy would be better for all of us taking it, if large numbers of others, that were interested, banded together and shared experiences and test scores into a common knowledge base. Egaceutical Corporation was started to collect information on individuals taking this therapy and variants of it and to promote studies at university medical schools as well to optimize this therapy which so far has been so beneficial to us. Larger scale brings lower prices. Our work, with EGA®, has decreased these prices exponentially. To date price has been the only problem voiced to me concerning this therapy.

NMN seems a better therapy presently since it is only one step away from NAD+ not two. NMN is stable in the blood, and is actively transported across cell membranes; NR is not. The main shortcoming of both by themselves are that they both need the two extra small molecule components added in EGA to turn off the feedback loops that turn off the Sirtuin enzymes in the human cellular repair system. The EGA patent includes all ways to make NAD+, including NMN and NR, so we are financially agnostic in the market competition between the two. The market holdup to date has been the price of NMN and NR, such that people buying these on the internet are taking doses far lower than those that were shown to have benefit in mice.

I want to make note of two categories of food based compounds that will be of benefit in the future as more knowledge becomes available. The first category is compounds that can be digested by beneficial microbiome bacteria that then produce beneficial compounds for you, its human host. Some molecules in this category are now being discovered and the understanding of these add to the more general concept that eating fresh fruits and vegetables is good for you. There are also negative compounds that some bacteria make that one wants to get rid of probably by getting rid of the bacteria that makes the negative compound.

The next category is polyphenols that activate Nrf2 that in turn activate 300 to 500 enzymes and molecules in your cells that include anti-oxidant enzymes. It was once thought that small molecule antioxidant molecules could increase reduction and reduce oxidation. Now it is known that these small molecule antioxidants can get in the way of turning on and keeping on antioxidant enzymes that are far more efficient at doing the job. Polyphenols in plants are quite often potent compounds in the turning on of Nrf2 and thus keeping your cells from the destruction of oxidative damage.

The molecules that turn on Nrf2 that have been getting some notoriety include resveratrol (in red wine) and the similar compound pterostilbene, apigenin (in parsley and chamomile tea), sulforaphane (in broccoli), curcumin (in turmeric), quercetin (in onions) and  ginseng (in tea). Even the diabetes drug metformin’s effect is probably due to turning on Nrf2. Each of these molecules has a bunch of other cellular effects and properties so they are not necessarily substitutable. Quercetin has been used for a senolytic drug and this brings the question of whether senolytic drugs are just compounds that turn on Nrf2 and benefit from the turning on of antioxidant defense systems and the correlated turning off of NfkB which lowers the immune response.

They include managing your exercise, sleep, microbiome, and diet as well as other tricks like heat and cold shock as well as syncing these approaches to one’s circadian rhythm.

An example of exercise is running, One hour of running gets you 7 hours of extra life. The concept here is that if you use something in your body somewhat regularly, it is assumed by your body that you will need it in the future so your body assigns energy for its use to keep it working well. That is why if you always run at a certain time of the day your body provides energy specifically at that time of day to run. In general exercise causes an oxidative shock to your body, if you exercise in the amount expected then your anti-oxidant defense system has the ability on hand to defend your cells from that shock. If you exercise more than expected, the excess oxidative shock it added up by a specific type of enzyme that then signals to Nrf2 to increase your antioxidant defenses. If oxidative shocks do not come within a period of about 5 days your body calculates it has been misappropriating its energy and turns down your anti-oxidant defense system. If you exercise way more than expected then you overwhelm the oxidation sensing system and the excess oxidative shock leads to cellular oxidative damage. These damaged molecules then need to be taken away and replaced. Remember cellular damage is cellular aging. The trick to exercise is to maintain or slightly increase your exercise to keep on your antioxidant defense systems or to increase them without making extra damage in your cells. So exercise like most of the other methods to reverse age are really tricks to optimize cellular pathways by keeping beneficial pathways turned on at full volume without incurring costly damage to turn them on.

Each muscle group needs this attention on a regular basis. Benefit has been seen with exercise of even muscle groups most people do not give much thought to like lung muscles, facial muscles and kegel muscles.

Exercise also changes your gut microbiome.

Sleep, especially slow wave non-REM sleep reverses age. Slow wave non-REM sleep is the natural time you repair your brain cells. Your brain cells work hard during the day and build up trash. So like an office with a night janitor, you clean up the trash during the night when your brain cells are not in use. This process physically entails the opening up of inter cellular passage ways and the brain cell’s trash is then thrown out of the brain’s cells and flushed from the brain in this wash cycle. So if you feel bad in the morning maybe the trash was not taken out. This is probably why drug addicts and alcoholics taking NAD+ drip for 8 hours a day are asked every morning how they have slept. When the therapy finally kicks in after 3 to 8 days, they then feel it in the quality of their sleep. Finally! the brain trash was taken out.

Changing your microbiome to that of a younger healthy person is theoretically beneficial. It has been shown that some organisms in the microbiome make you healthier and live longer and some make you unhealthier and give you a shorter life. Although changing the microbiome is known to be beneficial, in practice it is very difficult to change in any way and the complexity of the microbiome makes it hard to know how one should change it if you could. There are basic two ways to change the microbiome if and when science knows what we want the microbiome to look like. One way is to change the microorganisms in the microbiome and the second is to change the food that each of them eats. Both methods are probably needed together, although changing the food that they eat is probably more important and easier to do. The food that the microbes of the microbiome eat is called probiotics by those people that want to sell you this. It is known that the larger the number of plants you eat on a regular basis the larger the numbers of microbiome species you will have in your gut and on average this will make you healthier. This number of plants eaten dropped when humans went from being hunter gatherers to being farmers and human health deteriorated from this change.

You already know that eating correlates to your health since it is the ingredients and energy that you need to continually rebuild yourself. This includes the correct food types, the correct amounts of food, and also the timing of your eating the food. Recent studies out of Israel have shown that a grouping of individuals all eating the exact same diet had very different glycemic outcomes because of their different microbiomes. So it appears that the best diet for someone else may not be the best diet for you. All diets need to be individualized.

The first and still only age reversal that has been definitively shown comes from dietary restriction. This includes the subcategories of calorie restriction, protein restriction and methionine restriction. Fasting is an attempt to imitate dietary restriction while lowering some of the negatives of it. Two forms of fasting have immerged as promising. They include eating for 5 days and then fasting for 2 days. This is being promoted by Valter Longo, a professor at USC, who started a company to assist people to do this. The other is restricting the hours every day that you eat. This has been promoted by researchers at the SALK Institute. You can cut down your eating hours to 12 hours, 8 hours or maybe even 4 hours a day. Both methods have been shown to better health in multiple ways in small studies.

Heat shock and cold shock are an age reversal tricks. They both work in the same way, although cold shock additionally turns on the use of brown fat which makes heat and burns more calories.  Both turn on Serotonin stress signaling. Heat of about a 102 to 105 degrees F or cold at about 33 to 38 degrees F will denature, which means unravel, proteins in your body. This is seen as damage by your cells and so they turn on their repair systems. Turning on repair systems, as we have seen in exercise, is a good thing. So just as in the exercise example the trick is to balance the good with the bad.  Unlike exercise though you are not really signaling that you are using a body part, you are only signaling that there is damage in a part of your body.    2 minutes of heat or cold shock is probably sufficient to turn on your repair system, which actually only turns on after your body has come back to its normal temperature. Like exercise, any excess amounts of damage just gives you unneeded damage to repair. Remember damage is aging. Water conducts heat transfer better than air, and is easier to control, so it is probably better to use your own bath tub, with a thermometer, for this heat shock or cold shock than the nitrogen cold air spas that have been popping up for the wealthy.

If you are going to try to reverse your biological age, plan your strategy out before you start, preferably with a physician. Be sure to test your biological age and health before you start the therapy and then keep testing periodically along the journey so you can be confident that you are helping yourself and not doing yourself any harm.

The most important testing is before you start, preferably testing at two separate times, since this is what you are going to compare all results after this to. Make copious written notes on how you feel before you start, preferably for at least a month or two, along with your biological test scores. Although you probably think you will remember your prior-to-treatment body-state,  our work in this area has shown us this is not usually as good as written records.