undoing ageing

 

 These are truly unique wonderous times. For the first tme in human history, a true scientific path to undoing aging is within reach. Whine philosophy is minimized, scientific means within the capability of legal MD, irrelevant are belief systems of the beneficiary, like allopathic medicine effectiveness is the same for sinners, criminals and upright citizens.

There are many ideas on undoing ageing, referenced in past. I BRIEFLY MENTION THE ONES I WILL FOLLOW. There are other methods that may become more important in futute, so there is no total commitment on way to proceed, except lifelong commitment to evaluate. This attitude can be taken by me as a follower of research, not a researcher, but even here I have to restrict for saving time and reference lookup costs. I am smart enough to know my limitations and that certain references need to be followed, while others can be ignored for being support for simple things or similar or identical to ones already followed.

non-science methods?

All guru, tomes, witnesses are uniformly all bullshit. Have no time to waste even listening, leave interning!

parbiosis?

Veins of mice  of distinct age are sugrically joined to a common circulatory system. The rates of elder mice and younger mice are compared to similar free mice. Recovery from injuries, disease, stress and digestion of the elder mice are found improved.

One does not have to resort to parbiosis ghoulish effects to benefit. The same effects can be obtained by inserting young plasma. Plasma recovery is twice as fast as blood donation, without the fatigue felt after blood donation. This happens because the donated blood is filtered to remove the red cells which are reinserted in the donee. Plasma donation is simpler as blood type distinctions are missing and plasma banking is easier. Plasma can be sold twice a week!

The reason why plasma suffices is that it carries hormones and dissolved organics. What they are,is not known and there is no reason but science, to know. Clearly, the plasma can be enriched, equal to iv add of the chemicals. The whole idea of parbiosis is to undoing ageing, not knowing what ageing is!

One of the most useful effects of Covid is to use plasma in a similar way by transferring anti-bodies to the patient! Delhi has recovery bank blessed by the government. Certainly, the government will not object to repurposing the technology developed!

telomere?

While more developed (Columbia runs an age reduction trial, each member of test coughs up milion dollars), I will not follow because lab scientists have reported failures to now. Additionally, mice have perfect telomeres but live 3 years! The trial above, till results prove me wrong, is snake oil for the gullible!

https://www.prnewswire.com/news-releases/breakthrough-gene-therapy-clinical-trial-is-the-worlds-first-that-aims-to-reverse-20-years-of-aging-in-humans-300963496.html

Yamanaka factors?

Yamanaka-factors revolutionize and ethicize genetics. Determined by very hard experimental work, twenty five chemicals were very smartly  screened to 4 OSKC, which when applied to any DNA convert to its pluripotent form (that is prior to differentiation!)

Most exciting to me is Horvath clock demethylation of the epigenome. Horvath identified 373 sites in human genome DNA (experimentally) and showed that calendar age could be predicted from this biological age (bioage) to  within 3.6 years. You need to measure methyl concentrations at these points. Improvements by US companies has allowed them to claim within 1.6 years. Bioage is very important since it allows science of ageing. Epi-mark are better than DNA-marks! Most importantly, underlying DNA is fixed in the womb. This allows eventual scientific fountain-of-youth.

With proper schedule, the OSK (C only induces cancers) can be used at low amount which reduce ages of differentiated cells without losing the differentiation! Thus drugs can be made for avoiding ageing specific to differentiation.

One can even operate genitically in Cas-9 cuts and restore within the selected context of cas-9. The dajnger is lack of specificity of context which may appear many times. No one has implemented (to my knowledge) additional contexts by surgery. Idea is to remove small chunks through surgery, perform cas-9 updates and surgically replace the amount! The genetic manipulation is now surgically enhanced! This is not useful in the past but very possible in laproscopic surgery!

How Yamanaka factors are the best way.

There’s a preprint from David Sinclair’s Harvard laboratory, posted on BioRxiv but not yet published, with very encouraging news for those of us who think that resetting the epigenetic (methylation) clock is a path to anti-aging.

study from the University of Exeter in England focused on the reverse aging of human genes by focusing on senescent cells and what are called splicing factors. The latter is a type of protein involved helping genes express themselves normally, but as we age, the process of senescence, or a state in which cells stop dividing and slip into a state of growth arrest without dying, causes the cells to be inactive and essentially turn off.

Is Arun finally a mental gone case or harbinger of tidings that are essential to all friends. Answer is believability, in this case the top cetainly conservative science magzine the scientific American over 150 years! 

Aging Is Reversible—at Least in Human Cells and Live Mice https://www.scientificamerican.com/article/aging-is-reversible-at-least-in-human-cells-and-live-mice/

The researchers found that by applying a compound commonly found in wine and foods such as dark chocolate and blueberries called resveratrol, they can actually reverse senescence and cause the splicing factors to reactivate.

Research has indicated that aging is actually an epigenetic process, or in other words it is often fueled by nongenetic forces, such as the environment we live in. A 2016 study published in Cell found that by tweaking genes that turn adult cells back into embryoniclike cells (pluripotent), scientists were able to manipulate the behavior of human skin cells.

The researchers found that by applying a compound called resveratrol, they can actually reverse senescence and cause the splicing factors to reactivate.

One of things I do - 1gm reservatol per day, Rs. 6000 (thousand) for 6 month supply, copying Dr. Sinclaire (Harvard), discoverer of why we age! Redo nmn, nr, or nad when can get prescription for iv or injection form.

Can Science Reverse Aging? https://html.duckduckgo.com/html?q=yamanaka%20ageing

THE SCIENTIFIC THEORY OF AGING

What does a scientific theory mean? Absent a clear definition, every emfubar, while demonstrably an fubar, will claim science as part of a fubar belief system. Any statement becomes a scientific hypothesis only when it satisfies by negation the falsifiability test of Popper, and positively being a rational skeptic who never ceases a why. Ultimately the infinite regress leads to astronomical evolution which can be continued to about 10-21 second after big bang. What was before that, assumes there was a before, not necessary by any scientific theory. There are many cosmogenies that imply there was a before, but as a basic axiom. One of Cosmogonies in fact says that big bang is when time began. Note that time becomes infinitely slow at the speed of light and that spent by a photon despite coming from eons away is still zero. Neutrinos are matter traveling almost but not nearly light experience time, enough to change flavor in flight unlike photons which have same frequency fixed at creation time.

So what is the theory of Aging? It must be consistent with all known physics, chemistry and biology. It must be provable in the sense that some feature of the theory, on violation speeds up or reduces age. This must be simple enough to be allow performance in peer laboratories without requiring consultation with the author. In other words, experimental evidence can be collected and compared absent the author. This external repeatability is essential to science. I add another test peculiar to me - no external force (like God) may be invoked to explain all life on earth, this is not necessarily a denial of God, just the requirement God concept is not needed. All life can be explained (despite intelligent design pseudo-science) through evolution. This evolution-compatibility is my requirement and holds for Sinclair's theory. It even explains why all life on earth has a DNA basis, why fountain of youth is possible without time travel and why other forms of DNA do not exist. We might never encounter any other DNA.

It is a DNA based theory. The simplest form of consistent Circuits, despite other species based genes, is a fundamental requirement that the protein generated by a repair gene prevents the duplication of the DNA i.e. the cell. This exclusionary behavior is anti-simplistic understand of biology of evolution where replication is assumed to always be reason of existence of any lifeforms. True, but ageing is below a cell which has many species' dependent extra parts to the nucleus DNA molecule which is a giant double helix in all forms. Genes are simply small parts of the giant code. Operations are all done by allowing proteins to form by copying portions of DNA. The two cell level processes are duplicate and apoptosis. Duplication can be prevented internally by shutting of duplication gene while repair is in progress. The cell duplicates by unwind the double helix to 2 one strand parts, each of which forms a double helix by element duplication. The whole process takes time and exclusion circuit prevents duplication while unzip happens. This prevents error in the mother and daughter molecules.

Carefully note that any other DNA molecule, without the exclusion circuit, will fail after each coincidence of an error and replication. Errors happen all the time - x-ray, solar activity, stress, bad food etc. Unless DNA can recover some, the lifetime is milliseconds. Even with amelioration of errors, for animals, lifetime is few days to 300 years - cancers limiting life. EVEN TREES LIVE A FEW THOUSAND YEARS. Errors eventually add up and kill. The problem of ageing is too complicated to be solved by biology alone. But extending biological life can enable time for development of cyborg appendages to complete transfer to silicon life.

The fascinating corollaries to above are

1. The correctness of proof of above theory does not lead to any anti-ageing prescription

2. The systemic environmental interventions are all in the epigenome. underlying the epigenome is pristine DNA, as pristine as birth. Extending age and fountain of youth are the same thing.

 

Here are other possibilities.

HORVATH CLOCK

Distinct, but scientific, is the proof in 2012 by Horvath in California that all DNA genome and epigenome has marker sites whose methylation is strictly increasing and correlates with calendar age. The prediction rules depend on the species but are remarkably stable on mesenchrymal cells. For an individual of a spies, a table can be used to predict bio age TO within about 3 years of the calendar age.  A table can be prepared in advance per species to predict bio age accurately.

The strictly increasing methylation pattern has very few marks at birth. Amazingly, cells sunjected to yamanaka factors become totiplurasl by shedding the epigenome and the methylation marks of the underlying pristine DNA. Even the mesenchymal changes are not preserved. The cell can begin li8ge anew. But it is rarely a single cell! All the cells revert in unison, and what you get is a ball of cancer.

Amazement follows subsequent research. Of the four Yamanaka factors OSKC , the C is always cancer-genic. Of the 3 others, the degree of specialization removed depends on frequency and degree of immersion, more meaning more reversion. This has immediate applications.

1. The degree of age removal can be judged by starting and ending bio age. There are for example telomere based methods which predict a longer life from telomere restoration, but in this case too, the methylation removal happens. One can not cheat the Horvath clock,

 2. A genetic age reversal process follows by OSK based foods and medicine, subjects of future research.

aaq-capitalism

 One reason that communism flourished is that it was built around Marx researches which had a critical difference from thinkers then, a long researched empirical work to couch in scientific theory but suffers from significant selective bias since many empirical truths were ignored and only supportive facts were retained. In my vernacular, hge was a semi-scientist, a person whose theory is explanatory but inextensible.

I am tired of nuts who consider only public and private as two modes, in between is public-private-partnership my style which interpolates between private models, that were a big failure in South America and Europe. Or the communist public model in the erstwhile Soviet union and satellites. Or offensively successful economically in china which escaped the very anti-progress of Mao to freedom less china today. Without shame for my upbringing, comfortable upper middle class in India with many achievements despite family, surviving as a refugee from the USA but only as a TBI and great oppression by a University to a mentally disabled person. But I gained some clarity after 30 years as a TBI and passage of my father. My parents accepted me after 25 years of escape to a new country and despite my status and illness to a self-chosen minimal  existence and divorce.
America or post-Mao china are examples of my PPP model. Reason underlying my hatred for China, despite great progress, is the simple extinction of liberty. Or non-republican America is a practice of socialism and likely definite extinction of liberty there. It is very common and wrong to advocate American exceptionalism and socialism as solutions in the USA. Even more stupid is libertarian view that US progress is in any way related to Laissez-faire  and weak government. The reason as per me is like this talk here - Well done state capitalism https://www.ted.com/talks/mariana_mazzucato_government_investor_risk_taker_innovator#t-828883 . Even the solution presented here is very good - government must retain a definite fraction of ALL companies and eliminate most taxes. All people without jobs must be paid by the government even as the government sells unemployed labor to companies. Competition must be required in all government jobs, removing all restriction on political membership, and formulate non-discrimination rules. At least 2 persons must be in all rules, one from each collection in politics.

It is wrong to argue privatization without a funding by the government. Clever investment must be needed in this model since the government will starve without taxes. Will enough be generated for the government? Think of the government 20% ownership of all US companies and no taxes! It can be done! Is that ethical - any day better than taxes! Taxes are evil ways and much likelier to be unfair, whoever you are. Note the included destruction of publicity based communists and religion based tax free religionists! You can not hide director level discussions or great corruptions without some director squealing.

Amelioration of Ageing

NAD+ is known miracle chemical. In all humans, it declines continuously in ageing. It is known to be very important in Krebs cycle, which has a circuit of  NAD+ and Na-DH.
 

Na-DH.  NAD+ And NAD Benefits, Side Effects, Dosage And Stacking

The intravenous application of NAD+ is currently the only recommended therapy.

Augmenting either is good enough. NAD+ is made two ways - de novo (from amino acids) and synthesized (from Na-DH) while Na-DH is not made, just a step in the cycle NMN and NR are two precursors, both are made in body from vitamin B3. 

Flushing and Non-flushing (amide) form s of B3 i.e (Niacin,Niacinamide) are equally good. B3 effects, if at all, take 2 years. NMN or NR takes days.
Now there is bio-availability caution. NAD+ is useful inside mitochondria. Getting it there is hard. First difficulty is stomach-blood barrier. Next is Liver barrier. Next is cell-wall barrier from blood. Finally is mitochondrial penetration. There is an extra hard barrier for me - blood-brain barrier to fix ageing error for me - pseudo-Pakinson essential tremor. Past each barrier penetrates a small amount, measure in single digit percent. As you can see, minuscule amounts 0.00000001  percent will reach! one can raise it enormously by eliminating first 2 barriers by directly getting it into blood. Sublingual is one (as heart med, under 5he tongue). I failed in that. Another is nasal spray. Much better is iv or injection. Requires convincing and cooperation of a doctor, even getting injection/iv product.

 

Injection/iv product is very hard to get.
Published experience says iv form of NAD+ is under a day, while NMN lasts a week. USA has a breed called bio-hackers who try things on themselves and often suffer. iv and injectiblke forms of Nad+ are not for sale. One can get them  as powder and make injection forms by sterile water.Very bad idea as clear from this hacker!

more methods

Watch these links, they reflect only two other independent kinown methods  not dependent on exclusion circuit. No other method is known, consistent with all known science, physics, chemistry, biology and evolution. Without mercy, such a method is a religious farce and from a criminal mind.

This independence is great - do all at once, since each is independent!

parabiosis

Parabiosis? https://aaqg-arunarya.blogspot.com/2020/08/to-be-done.html

Parabiosis is surgical joining of two mammals such that their blood systems are joined. Tried successfully on two mice - one young and other old. The repairs in old were like young. Don't get nightmares as the effect survives plasma infusion. A bad idea if just extracting young blood without replacement. Exchanging blood worsens the young. Now what?

Escape from bio-criminal scientists of Nazi Germany is possible by undone experiment that likely will be done eventually by me!  Plasma add is well developed technique where the blood is drawn from a young but distilled to plasma and red blood cells. All the cells are immediately returned to Donor. This technique allows the recovery of donor twice as fast! The red-cell-sans plasma has all the benefits of whole blood! Serum banks in Delhi are made to donations from recovered covid infected. The plasma technique works for most diseases, was in act routinely used before antibiotics.

telomere

Telomere? https://aaqg-arunarya.blogspot.com/2020/08/to-be-done.html

A telomere names the end of DNA like thin fluffy ends. There is progressive shortening on every rebirth of cell. After 30-40 doubling,the size becomes so small that cell wont double any more. The length of Telomere correlates well with bio-age of the species. It is governed by the chemical Telomerase.

Lengthening telomeres for humans correlates to lessening of methyl marks. This is another way developed even more than Sinclair ways. 

Lengthening fully makes cell immortal i.e. cancerous!
One of the largest studies to date on telomeres shed some light on telomeres’ effect on a person’s health. Researchers collected saliva samples and medical records of more than 100,000 participants. Their findings showed that shorter-than-average telomere length was associated with a boost in mortality risk — even after adjusting for lifestyle factors like smoking, alcohol consumption and education that are linked to telomere length.

It stands to reason that if science found a way to increase Telomerase production, telomeres would remain long, lengthening life spans and possibly reducing the risk of some diseases.

In fact, one 2010 study published in Nature performed on rodents seems to confirm that theory. Mice engineered to lack telomerase aged prematurely and became decrepit. But when the enzyme was replaced, they bounced back to health. By reawakening telomerase in human cells where it’s stopped working, normal human aging could be slowed. “This has implications for thinking about telomerase as a serious anti-aging intervention,” said Ronald DePinho, a cancer geneticist who led the study.

However, there are still serious doubts about whether reversing or slowing down aging via telomerase activity is the answer. Because while telomerase does lengthen telomeres, in humans with cancer, the enzyme helps existing tumors grow faster. At this stage, it doesn’t seem we know enough about safely harnessing telomerase to ensure that it works only to lengthen telomeres and doesn’t actually stimulate cancer. Somehow the DNA genome and epigenome lose methyl marks.

 

ageing

alivebynature discount coupon 4292305
Aging products
pterostilbene better than resveratrol - more bioavailable from putting two methyl groups 200gm=1000gm of resveratrol
pterostilbene https://www.amazon.com/dp/B005ACNW5S
https://www.amazon.com/Strength-Pterostilbene-Capsules-Naturally-Longevity/dp/B07GCBWB83/ref=sr_1_8?dchild=1&keywords=pterostilbene&qid=1597490244&sr=8-8
nmn VERSUS nad+ : BASED ON EXPERIENCE BY UNBOUGHT USERS
bad idea to qualFF nad+, must take in iv form, or nasal spray to bypass liver
nad+ and nmn do same thing - nmn becomes nad+, but nmn injections every week WHILE nad+ every day!
NO iv/injection products BUT atulji sister has agreed to help. Prefer nad+ way because it crosses into brain, will/must improve my parkinson-like shakes now quite bad. Important test for me,  will know after 6 months.
Some references

To be done

Tobe done, whenever

No one can speed me up

Aging fight: call to arms

I am a scientist, was in bell labs, spoken at Harvard and was assoc prof at university of Massachusetts for many years. I was hit by TBI which I fought as a scientist and had partial recovery in 2020 from TBI after the shock-death of father! Important to give you fast believable intro to me as an atheist scientist who believes in indefinite life, healthy because of current efforts and future age reversal, no longer sci fi!

This is after Nobel-assured research by Dr. Sinclair at Harvard in Aging theory of information. What he has shown is that Horvath clock counts marks in cellular genome DNA and epee-genome IE epi-DNA as well. Aging is simply senescent cells from proteins forgetting where they should repair DNA cuts and/or where to return

https://aaqg-arunarya.blogspot.com/2020/06/aging-proofs-digilog-how.html

DNA does not change after birth - way before that! Epigenome has finite life and genes coding recovery lose proteins to wrong places. Genes make RNA then proteins. Tight coiling of DNA at some places happens due to proteins built by some genes for repair DNA - called gene shutoff. The repair proteins must prevent  generation of new cells while repair. This exclusion circuit is characteristic of all DNA in every life form. The evolutionary advantages are overwhelming, so that only DNA with the atheist scientist who believes in indefinite life, healthy because of future age reversal, no longer sci fi!

In any case, DNA does not change over life while epigenome changes. By stripping away epi-layer, you not only get ageing stop but age reversal!

https://aaqg-arunarya.blogspot.com/2020/07/amelioration-of-ageing.html

Horvath was a bio-statistician. Using primitive of 2012 AI, he managed to get very close bio-age numbers to  the actual calendar age and was very accurate in predicting remaining life for most from age-caused demise. Since then (to 2020) other markers and sites have been used to build other clocks. They cost $300 to $500 in USA, amazon-India used to do them but no longer, in fact no one does them here.

I am starting a company to survive on doing Horvath readings on the side and mouse-test of serious proposals on the side, including novel once. Rs. 10,000 per test is doable and should work at Indian
salaries. Certainly meshes with self-sufficient movement of today. Chemicals can be imported till production happens here. Reading microscopes is where costs are lower.

Horvath clock are absolutely important for scientific investigations in to ageing ideas. I know that metformin+acarbose extend life by about 10 years but the number is vague and can be sharply determined.

I also have a revolutionary idea that will certainly improve modern medicine allopathy. FDA tested drugs are used. There is NO pre-medication test of drug appropriateness! This is done in some cases (penicillin verbal quiz) but not enough! I have determined by experience that while I am not sensitive-penicillin-freak, using it to cure teeth-pain after and during root canal procedures makes me throw up food, while TZ is no longer effective. Ceftum is the answer. Why use sinusitis drug in root canal?

 This double-masked, multicenter, randomized clinical trial compared the efficacy and tolerability of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial maxillary sinusitis. A total of 263 patients with acute bacterial maxillary sinusitis were randomly assigned to receive 10 days of treatment with either cefuroxime axetil 250 mg twice daily (n = 132) or amoxicillin/clavulanate 500/125 mg 3 times daily (n = 131). Patients' responses to treatment were assessed once during treatment (6 to 8 days after the start of treatment), at the end of treatment (1 to 3 days posttreatment), and at follow-up (26 to 30 days after cessation of treatment). Clinical success, defined as cure or improvement, was equivalent in the cefuroxime axetil and amoxicillin/ clavulanate groups at the end-of-treatment and follow-up assessments. Patients in both groups showed improvements in symptoms of acute sinusitis at the during-treatment visit. Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events than treatment with cefuroxime axetil (29% vs 17%), primarily reflecting a higher incidence of gastrointestinal adverse events (23% vs 11%), particularly diarrhea. Two patients in the cefuroxime axetil group and 8 patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events (P = 0.06). These results indicate that cefuroxime axetil 250 mg twice daily is as effective as amoxicillin/clavulanate 500 mg 3 times daily in the treatment of acute sinusitis and produces fewer gastrointestinal adverse events. cefuroxime axetil, amoxicillin/clavulanate, acute sinusitis.

Comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of acute bacterial sinusitis

After patient-intervention(IE by me), another antibiotic eeftum is used, known to some dentists only.. This should never be patient duty. Instead of list of possible side-effects, the physician must use a pre-medicine to know expected side-effects. It can be included in FDA-approval time as a sub-phase to figure out expected side-effects. Double bind tests must determine effectiveness in best adapted patients, the med may still be useful despite overall flunk.

I also have a another revolutionary idea that will certainly improve modern medicine allopathy. FDA trials weigh each participant equally. That is in spite of knowing that effectiveness may depend on ethnicity and sex of the participant. That information must be kept and double-blind results factored by population profile. India can and should establish post FDA approval agency that conducts trials on FDA-approved drugs only that determine efficacy on population profiles!