Be a careful reader, digest 20 years follow up, made public before a book for thoughtful comments, missing points, and questions. Will attribute, with name and reader chosen link in the book.
Why believe you at all?
Like all skeptics, I claim I know not Aging in totality, yet enough in 20 years to know a lot more than 99.99 doctors in this small subject, enough to speak about aging to answer intelligently related questions and suggest doable things. Unlike scientists in general, I believe in my work to the extent that I age, refuse to, and I apply my prescription to myself. Self-application trumps any FDA.
Aging reversal criminals?
Why does one age, what changes, and how does one fix it; it is natural questions, easy to give stupid obscene criminal answers based on religion and pseudo-science, must be defended against criticisms, and separated from truth. The answer is easy to do in science and agnostic with respect to whatever you believe in, exactly like medicines which treat independently of what you think, rest are not considered medicine for aging by me, independent of what law says. Thus, some psychiatric procedures are not called science, but now easy criminal identification is the issue. Remember always that I forbid any deductions to be made outside Aging.
How know you are not a criminal?
Basic to separation, not truth logic, is to realize that classification is not into true or false, but follow or not, with an estimation of risk. I assume that my followers will consider my estimation and unfiltered experience to be reliable prior to the FDA seal of approval. Repeated series of (why?) sequence forms an infinite sequence in non-science but is very short in science which depends on empirical axioms. The only way science fails is wrong axioms or missed dependence.
Heroes and who/why is one?
There are only 4 double Nobel Winners, only 6 Nobel-worthy Gentlemen and ladies in Aging. These are all heroes of mine since they worked on after the first prize eligibility without tiredness and produced a result comparable to the first. Dr. Sinclair for resveratrol and NMN. Dr. de Grey for SENS and 7 fix model. Dr. Horvath for DNAm/Grim age and generalization to Eutheria. Dr. Yamanaka for common DNA under specialization and OSKM factors. Couple of Drs. Conboy for parabiosis experimentation and debunk of natural suggestion. Only non-controversial judgments of these cause me to rethink. All other judgmental are yawn-worthy.
The lists above are extensible, as under evaluations are paradigm-busting single noble-worthy are Drs. Fahy (TRIIM, await TRIIM-X) Katner(E5, await rat reset). Because Drs. Conboy conflicts with Katner E5, I feel that young blood is a misdirection.
What is aging?
Aging is easy to state: DNA molecules in every cell, in their nucleolus compartment, have an epigenetic layer that overlays the DNA and turns on/off genes and turns them to be specialized. It communicates with all other cells and processes outside the nucleolus through oneway mRNA copied and selected by signal proteins. The very big statement here is that different classes of cells in anybody are identical to DNA is overlaid by epigenetics that specializes in cell form to be. The deepest questions are all in molecular genetics. There is external magic outside nucleolus but within cells. Two basic bodies, among many, are ribosomes and mitochondria. First unites with mRNA to produce requested proteins. Second has own 13 unit DNA of own, participates in Krebs cycle, generates energy in ATP-ADP subcycle.
Why do all cells have the same intact DNA?
There is much proof of segments. The indivisibly of original intact DNA is suggested by created division of a single zygote. It is a lot easier than chemical specialization where errors can not be rectified. There are no precise processes in biology. An error will be common and only error correction will yield the right result mostly. This is a basic belief from a computer scientist like me. Evolutionary survival of perfect exclusion of copying from repair is so extraordinary billion years ago that I don't expect any other life in our galaxy. Where are they? Nowhere in the galaxy for minutes lifetime of best-evolved DNA. Conclusive proof to me is that every cell, using Yamanaka factors, can be made pluripotent!
What are aging science fruits expected?
Everything scientific is very hard to postulate since the scientist must accept all logical derivations as well. There are three remarkable derivations. One is that age-reversal is just as easy as age-slowing. The second is that wish death or biological immortality is possible by repeated cycles of age-reversal and re-aging. The third is that chronic diseases, cancer, and aging are curable diseases beyond just the treatments that work in modern medicine and a team of two of an MD and aging scientists can work wonders and cure the incurable.
Aging is from the steady breakdown in epigenetics error-recovery. A cell uses methylation for mutual exclusion while repairing and over time, a very smooth process of methylation is built in all disconnected cells. This dynamic statistical steady-state process converts cells, on correction failure, to senescent cells. In youth, due to the activity of immune cells, removes such cells by autophagy. The decline proceeds steady-state to around 65 When new white cell production ceases and completes up to 80 as white cells already produced decline. Up to 95 is another decrement phase. After 95, there is a steady-state failure but a constant probability zone. Is this theory of aging (Dr. Sinclair) programmed or damage-accumulation?
How does it work?
Old age is plagued by constantly increasing strength reduction from the failure of mitochondria in ATP-ADP subcycle, ie energy. My risks are for curing the incurable chronic diseases, only for long life in the minority. But then cancers-prevention and aging are chronic disease cures, so I believe. Rather than cause possible cancers, I think my protocol is cancer-preventative as it removes senescent cells!
Senescence leading to just missing cells is one part of aging. The reality is far worse, since senescent cells, not only occupy space but also generate hundreds of chemicals of SASP. And make neighbors senescent. SASP is mostly evil. The worst chemical in it is CD38. It reduces NAD+ required by many subcycles of the Krebs cycle. The proof is a steady drop of NAD+ with age and a boost of CD38 with age. I, self-use, also work on other dropping chemicals and rising villains. But here limit to raising NAD+ by NMN and reducing CD38, doable by fisetin.
How does safe growth happen to adulthood, what happens after?
Growth happens through growth enzymes SIRTuins (1-7), AMPk, and mTOR manipulation of stem cells. Safety is the Immune system through white blood cells everywhere. The abode for immunity is the thymus gland principally. It functions best at the age of 10-15. It continues to become useless fat, called thymic involution, a process that ends as an adult. Growth comes from stem cells. They reduce in numbers but do not die. They turn off at the start of adulthood by expressing signal molecules obeyed by growth enzymes. They are needed for some wound repairs. White cells were needed to battle viruses, bacteria, harmful processes, and diseases. Now I descend into weakening immune and Covid-19 challenges, scared even after 2 vaccine shots!
It follows that restoring the growth factor of Sirtuins, AMPk, mTOR is central to Aging improvement, and restoration of the thymus is central to the first procedures to reverse aging. There is never any magic. Aging strategies are boosting the growth enzymes, repairing or removing senescent cells, any case fixes SASP and fixes the Thymus. Or do many at once, these appear to be independent. Unlike other aging doctors, I do not need to research every method independently. I assume heroes are right and compose them safely my way. One way is to build a model of each and constrain oneself by safety in low dosage to safe categories which likely don’t interfere. That has allowed me to compose and limit my risk to unknown effects at high dosages. Known interactions are avoided. Benefits mine, dangers mine, have lived many years, not ready to quit just yet, but will fight with unknown danger to escape near-certain decrepitude.
Can Thymus be restored? TRIIM says yes, TRIIM-X will prove it. I propose NMN to boost NAD+, Fisetin to reduce senescence hence SASP. Perhaps mix of HGH and DHEA for Immune. Tell you after I try it after TRIIM-X and confidant permission of my Diabetes MD.
How does one fix it?
There are only 3 ways beyond what elders say. These are slowing methods and will not lead to a reversal but may add 18 years to life and 40 years to healthspan. These are well-known but only stated by a well-intentioned meta-moron and hence condemnable for assuming the preaching targets are morons. These are calorie-restriction, exercise, and only one meal, however heavy and whatever contents. Last is for slow adoption as is the first. Exercise is hard and requires supplements here, with some CR and exercise strength will return to allow low dedication CR and exercise. These affect mTOR, AMPk, and Sirtuins (sirt1), enzymes in the body as in the title picture. The entire left chain awaits TRIIMX.
My goal is to say to CR and exercise cheats, chemical supplements will do enough to enable these! It is not your fault you are cheats but of subhuman gurus that treat you as morons and psychologically diminish you!
Which FDA empiricism forms your basis?
No matter what I suggest, You must have the question in mind - what is the FDA proof of it and how will the suggestion interfere with existing and future prescriptions? The second part is easiest to answer, FDA has no interference data, you are on your own. Also true for question: why will be chemicals not cause cancer in 20 years! There is some risk on all medicine. You must reduce risk, always balance with no treatment and disease treatment.
Who are you?
My own reality is aging terrified. I am not a professional doctor or drug expert, or manufacturer. Yet I try, aware of the risk, based on extensive skeptical reading over 20 years, on myself. Dangers is not just a risk but central to my purpose. The best is to think of me as an FDA rational skeptic, only extending whenever reasonable.
Here is one way I consider FDA or doctors less than me. Every drug after 2000 is cancer suspect and avoided. Reliable history of uses before 2000 is great. Stevia (1500 year Peru use, 1970+ japan use, Europe) is OK. K2 (MK-4 legal in japan) in MK-7 form okay. Metformin is recommended prior to TAME. Only stupids wait for FDA, okay, to be followed except on narrow Aging grounds. A barrier, not a wall,
How do you know your recommendations are safe and efficacious?
Two basic goals are prevention of the need for MD prescription, hence supplements only; and efficacious bioavailability that requires right amounts and liposome only. Only an aging scientist can determine the doses and efficacy of products.
Another safety is supplements-only from safe classes, do assume large dose risk small, also small cross risk from interference, now or later. There is a genuine element of arbitrariness in some chemicals that are declared priori safe. But that is where 20 years of experience come in.
1. GRAS (generally recognized as safe).
2. Widely distributed in civilized foods and vegetables.
3. Present in significant amounts in human body processes, specially bio-flavenoids.
4. Extensively used over 30 years, clinically proven safe, no known evil side-effects, useful efficacy on public use, metformin, and acarbose.
Are your recommendations safe and efficacious?
NMN. is significantly precursor to NAD+, intermediate between vitamin B3 and NAD+, considered better than NR by Dr. Sinclair, so #3, modifies Sirt1. Fisetin is largely in strawberries and apples, so #2, safe senolyte. Metformin is #4. Efficaciousness arises from two heroes of aging, Dr. Sinclair who has reported extensively, and Dr. Audrey de Grey, who imagined reducing as action if senolytes on intra-cellular junk and SASP. Both act separately from each other, have different theories, and have been successful. I combine boosting with fisetin senolysis and NAD+ boosting. I argue to myself that boosting and senolysis are largely independent processes, unlikely to carry additional risk by my thinking by interference with future and current medicine, and likely composable. Metformin is for AMPk.
CaAKG is for mTOR, as is low dose Rapamycin. Not yet, may not be needed. HGH and DHEA for Thymus. That may be needed, but awaits TRIIM-X data.
What is wrong with mm?
If one considers Allopathy versus Indian AYUSH rationally, the essential reason former success is small causation (fungal, bacterial, and viral) i.e. germ theory. They and such models fail miserably in most psychiatric, chronic, cancers, and aging diseases. I call Allopathy applied to everything modern medicine or mm. Psychiatry has become a separate part, with treatments as others with treatment, not cures. The theory of treatment is to apply FDA passed medicines.
Most Allopathic medicines have other disease side-effects, leading to a short chain of problems. Only a person capable of recognizing many illnesses can deal with medications. Few cures for non-germ diseases. Aging science uniquely may have cures, healthspan extension is a pleasant but unrequired gain! So what is the effect, incurable diseases or aging, I don't care which causes either. Everything but metformin is naturopathy, so is metformin and acarbose, but not by USA law. Best think of my cell medicine as separate from mm and contains orthomolecular medicine, still alive.
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