Saturday, February 27, 2021

Joining all the threads

What has led you to believe in your own paradigm as a fanatic?

Over the last 20 years, I have patiently and in great detail pursued every scientific (as per me)result from anyone claimed by me scientific. This has included 5 year blind paths at believing wrong interpretation of parbiosis experiment of heterochronic parabiosis by Conboy in 2005 by Stanford faculty, who saw magic proteins in young blood, isolated, productized, and packaged by their companies. What gave me pause was wait and see of non-existent results. Why I believe in blood dilution theory to the point of experiment with myself is FTD belief in results (Dr. Sinclair re chemicals), Conboy interpretation of parbiosis, potential benefits to self and loved, and high safety of TPE. The worst is nothing exciting happens. If TPE was not FDA approved, or TPE criticized by Dr. de Grey, I would not volunteer!

In 2016, a SENS Research Foundation study in the lab of Drs. Irina and Mike Conboy at UC Berkeley gave significant support to the Dilution Solution, and they have now published a pair of new studies showing that literally diluting the aging plasma with injections of saline plus replacement of the relatively inert transport protein albumin promotes even more dramatic rejuvenation effects on body and brain

How do you know you are complete?

He [Alex Zhavoronkov, PhD, the chief scientist of the Bio gerontology Research Foundation [and the CEO of an artificial intelligence company Insilico Medicine] also proposed a strategy for re purposing known geroprotectors such as rapamycin, nicotinamide riboside, nicotinamide mono nucleotide, metformin, and other drugs with the known safety profile for prevention of SARS-CoV-2 infection. The following is the quick British paper. [he terms Cov-19 disease gerolavic, I agree]

Clinical trials of low-dose rapamycin to protect elderly from COVID-19 proposed

rapamycin is dangerous

I have discussed all except rapamycin. It is available for immune protection from transplant, by reducing immunity at 2 mg/day. Anecdotally, 1 mg/day reduction is enough to defeat immunity loss! Only proper FDA test can tell! That it is legal for something, by FDA rule, any MD can prescribe it for anything! It is controversial and doer not interest me now. Incidentally 3 pathway protein group for aging reduction are (each a protein group) Sirutins, PARP, and mTOR (proteins IN mammalian target of rapamycin), which indicates very old claims re rapamycin, solidly warned against by FDA, yet people quaff it anyway, for aging and cancers, (Hail Mary effort)!

Sirolimus - Wikipedia

This Obscure, Potentially Dangerous Drug Could Stop Aging

The first is rapamycin, which was originally developed as an immunosuppressive. But when taken at low doses, it's been found to extend the lifespans of mice by around 15%. This is accompanied by the slowing of multiple age-related changes, such as tendon stiffening and liver and heart degeneration. In other animal models, it's been shown to slow the development of Alzheimer's and Huntington's disease. In older humans it dramatically improves immune function and vaccination responses.

Rapamycin slows aging by inhibiting the protein mTOR, which regulates the process of protein production in cells. Inhibiting it allows cells to recycle damaged proteins instead of allowing these to build up. Normally, mTOR allows these damaged protein cells to build up because it requires less energy for cells to continue building more new protein over recycling the old ones. But this buildup of proteins in cells can mean cells don't function as well as they should. Inhibiting mTOR can enable cells to continue functioning properly.

So let us recount my derivations.

Dr. Sinclair is of Harvard. He is unlike all scientists, free of money concerns and safe unconcerned like them. He has a theory (not subscribed universally) for aging which justifies my NMN (not NR) and pterostilbene (not resveratrol), metformin and k2+D3. Targets are linings, mitochondria and calorie-restriction. That is my drug effort. D3 is less vitamin and a more full-fledged hormone.

There is a strong argument against any theory of damage accumulation as from the latest Horvath bomb-shell, as quoted here "Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several species, it is difficult to ignore the likelihood that a defined and shared mechanism instead, underlies the aging process. To address this, we generated 10,000 methylation arrays, each profiling up to 37,000 cytosines in highly-conserved stretches of DNA, from over 59 tissue-types derived from 128 mammalian species. From these, we identified and characterized specific cytosines, whose methylation levels change with age across mammalian species. Genes associated with these cytosines are greatly enriched in mammalian developmental processes and implicated in age-associated diseases. From the methylation profiles of these age-related cytosines, we successfully constructed three highly accurate universal mammalian clocks for eutherians, and one universal clock for marsupials (other mammals). The universal clocks for eutherians are similarly accurate for estimating ages (r>0.96) of any mammalian species and tissue with a single mathematical formula. Collectively, these new observations support the notion that aging is indeed evolutionary conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new and compelling evidence."

Parbiosis paper of 2005 leads to Conboy paper of 2020 with surprising bad blood causing the age problems, rather than magic proteins in young blood. That leads to my demand for Blood dilution by TPE. Note that human results are in the pipeline and Dr. Conboy advices against precisely me. However, my loved ones can not wait and my own debilitation for 2 or more years. The risk is low and benefits huge, and I believe enough in my medicine. So the conversation with doctor uncle will decide. As expected, march is here for Covid-19 vaccination, and I must experiment with 0.5 mg rapamycin also, in conjunction with NMN.

Work in California on Yamanaka factors based medicine and supplements are essential to eventual forbid of death through brain download. I just track FDA and UC Berkeley/Stanford and other big news, but read them skeptically. Anecdotal by otherwise known people without significant controversy, not other ad tricks (specially by professional advertisers, all considered sub animal emfubar).

Risks of TPE

Low blood pressure
Shortness of breath
Metabolic alkalosis. This can cause a headache or seizures.
Bleeding
Increased risk for infection because your normal immune system proteins (antibodies) have been removed
Too little calcium in the blood (hypocalcemia)
When non-plasma replacement fluid is used: too little potassium in the blood (hypokalemia)
When donor plasma is used: Allergic reaction or disease transmission

Thursday, February 25, 2021

Prepare for advice from doctor uncle

Alzheimer's disease and dementia

Why USA thrives

Edited quotations in NBE

Edited quotations in NBE

Apheresis is a common procedure and usable in many illnesses, done without many consequences on the receiver, who can do it every month if one considers the same time as the donor, who loses the plasma in the usual scenario. Albumin liquid with cells and platelets saved from blood is advised to the donor to replace the lost plasma. Same is done in NBE, except that I will also add NMN.

[Merck...]

Apheresis can be used to

Obtain healthy blood components from a donor to transfuse to a person with a disorder
Remove harmful substances or excessive numbers of blood cells from the blood of a person with a disorder (termed therapeutic apheresis)

The different components of blood that can be separated include

[...]
Plasma

[...]

The [...type of] apheresis that [...is done is]

Plasma exchange

[...]

Plasma exchange

In plasma exchange, the person's blood is removed, and the plasma is separated from the blood cells and platelets. The plasma is discarded and the blood cells and platelets are returned to the person along with a plasma-replacing fluid, such as albumin.

Plasma exchange is used to treat disorders in which the person's plasma contains harmful substances [...]

To be helpful, plasma exchange must be done often enough to remove the undesirable substance faster than the body produces it. However, apheresis is repeated only as often as necessary because the large fluid shifts between blood vessels and tissues that occur as blood is removed and returned may cause complications in people who are already ill.

--------------------------------------------------------------------------------------

Facts About Apheresis

1. How Apheresis Is Performed

A medical machine is used to draw out blood from the body – usually the arm.

The machine then separates the components of the withdrawn blood. Only the plasma or platelets components will be collected.

The rest of the blood is re-infused back to the donor’s body.

2. Why Apheresis is Performed

[...]

5. Amount of Blood Removed During Apheresis

The amount of blood removed will depend on the type of medical machine to be used in drawing out blood during the procedure.

[...no doner]

6. Time the Procedure Takes

[...no doner]

7. Apheresis Experience

The procedure is painless. Research has it that most patients who’ve underwent apheresis feel tired after the procedure.

However, it does not last long for normal body activities to resume after approximately 24 hours.

8. Side Effects

The side effects of apheresis include: dizziness and a little pain at the point where blood is withdrawn.

A person who is sensitive to anti-coagulants feels some itchiness on the lips after the procedure. The side effects are short-term and have no particular effects on the donor’s health.

9. Frequency of Performance

The advisable time period for having another apheresis procedure performed on the donor who had the same donation procedure is roughly 3-5 weeks.

[no info on receive frequency]

10. Advantages of Apheresis

[...no doner]

-------------------------------------------------------------------------------------------------------

Equipment

Why USA thrives

It is a colored view of USA, why it thrives, why I love it despite remoteness, why my lessons are central to my self view, weltanschauung, and my politics. The closest I find as ideal is Carnegie who epitomizes "teach a man to fish charity", than "gift him food". He gave a lot to establish free public libraries to many town, but librarians paid by the city government. His perfect man, never knew him by words, but self derived, established a huge school, but run by RSS, and three clinics for homeopathy, Ayurveda and Unani, all free but run by the government of UP as deeded charity. Clearly different from me (all medicines opposed) but so is Carnegie in US, still opposed by all fellow travelers. Rather than destroy, I will add free modern medicine clinic. In fact I may do it from anti-aging wealth!

I could identify my legacy, but this is about why USA thrived. As a superior business man ex-president Trump divined, no matter what your ideology, you will buy some items from USA in at least 4 classes based on innovation, military equipment (else enemy fucks), soft arts like movies, software, books etc (else boring entertainment); space access (else no satellites) and drugs (illness fucks even kills). You will buy them even if you have to eat grass. Modi bought many military items, eventually crushing china. Like a superb tactician, he has switched to self reliance. Farmer agitation has not driven him to USA stupidity (average farmer earns 1.5 times the average, based on competition control (3 laws) and subsidy for MSP like prices on unlimited produce).

The country is not managed! It has become truly universal with time and social equality. It remains a collection with recent hierarchical immigrant communities with mixing (with all the social problems). Inter-operation is competition friendly and must be forced by requiring public explanations to contrary steps, which can then be used in any court. The essential tool is unfettered competition with no steps reliable in courts on books, all capable of being competition attacked.

The USA country is a joy to live for wide reach of successful business and consumer travel on slow dilapidation, still awesome highway system, built in the 50's. India is following the same script with massive growth in highways and rail network. Even my suggestion for double decker trains is being worked on, raising some cross-track bridge path. Railway works on universal electrification of all engines, away from diesel polluters. Rapidly CNG transport and tractor revolution despite arm twisting on paraly burn!

With the falling cost of LFP (LiFePO4/C) batteries, another paradigm change happens in transportation fuel with reusable solar and wind. I am ready to invest in sea based floating solar batteries. H fuel is still sci fi. India and USA both have enormous coast lines. LFP enables electric transport! Economical wind power. Off-grid homes. These move from Sci fi to Rational economics-free speculation RSEF. [A Tesla slide presented during Battery Day revealed the $25,000 EV it plans to sell in three years will use LFP batteries, which makes a lot of sense. ]

Elon Musk is modern miracle man with several paradigm changes under his belt, feeding to themselves. Electric cars, homes and batteries by LFP, boring company city traffic and hyperloop long distance! And then reusable rockets! I summarize them as paradigm changes to fuel, city transport, intercity transport, utility backup and rockets. Achieving Doer rather than me as mere document er. If I succeed in harnessing government help, perhaps I become another 21 century paradigm changer in health span.

Wednesday, February 24, 2021

Alzheimer's disease and dementia

Alzheimer's disease and dementia are certain of some unspecified of my class, could be me. What happens when they do? A link, reachable by clicking title, references AMBAR, the only reference I could find of TPE (Therapeutic Plasma Exchange) on humans. TPE is FDA approved for auto-immune diseases, hence safe with unknown efficacy. My use, based on DRS. Conboy of UC Berkeley, un=recommended (use concerns) by them, but recommended by me for people who have nothing to lose, IE suicide doers and aged on deathbed, but these are psychological states and not diagnose-able as per me. With any sense, you are better off waiting for aging age types or ageotype which will make TPE good for you. Searching for reference I ran into a web link to Dr. Dobri Kirprov, also co-author in Conboy paper, and the TPE expert. My aging world sanes of SENS of Dr. de Grey and Dr. Sinclair has grown to include DRS. Conboy of Berkeley (parabiosis expert) and Dobri Kirprov of San Francisco (TPE expert).

That said, the mental problem is acute for me. I could not help my father. But I can my mother, convince her to take TPE. She does not trust my medicine, despite all belief in me. She has committed to following me, if it benefits me. I am all set but just one problem - I can push the matter for 5 years based on acuity of all my symptoms. In my judgment, she can't. World will change by then, more will be known, why am I interested in becoming an aging doctor, affect others than just me? Perhaps my encryption work will expand to fill all my time, now that quantum computer safe has been provably added! The answer is that for minuscule risk, my mother will follow me after near certain improvement. Do I take the very small risk? Mice and similar experiments are clarinet to buffalo!

The answer came to me after a lot of thinking: talk to the doctor uncle, has always been helpful to every one in the family, me included. He is Prof. G. D. Agrawal kind saint and smart, likely to understand the moral question and understand the medical benefits and issues. Even better, he might just know some TPE doc in Delhi and refer me to him. Covid-19 has done that to Delhi.

Tuesday, February 23, 2021

Federal Indian govt. in Aging Research

The Latest link

Clicking links is req1uired for understanding of rationale for what I say. Particular interest is in what initiatives GOI should take. To be mailed/e-mailed to PM Mr. Modi, CM Yogi, Director IIT Kanpur, class-of-75 hoping some reader will forward properly.

Why should GOI take initiative NOW?

Two aspects are initiative in-this-direction and now. Principal DIRECTION argument is engineering - likely success of California efforts makes it risk known-unknown. Now is from patent restrictions that will hobble Indian efforts soon that will be launched anyway. The efforts also bypass Mexico, likely the beneficiary of California initiatives, which will attract California business of Medical Tourism, as opposed to Greater NOIDA or rest of India, likely to become a center soon. As far as US medicine goes, both Indian and Mexican medicine are Pitts, but Indian Medicine is likely to be better controlled and better destination for Arab and European customers. The amount of sales moment reliable word is out that 10 year healthy health span extension is likely by UP based hospital (Also assuming more interest as Greater Noida soon sees film city and Zaver airport). Whatever I say is likely hot air for all usual doctors, it is all based on genetics/DNA and is paradigm shift beyond germ-theory to Aging undoing by DNA medicine and surgery beyond stem cells, that itself is a new paradigm!

Assuming GOI decides to take initiative now based on some understanding of the aging relative efforts in California, medicine being developed based on 3/4 Yamanaka factors, relevant questions are

1. Can the effort be funded within Indian politics?

My model is the ARPA agency, responsible for nearly all major efforts in the last quarter of century 20 including GPS and internet. It is not Capitalism of that era, and certainly nor Socialism or Worse of that era. The Basic question is development speed despite political reality of uniform funding. Non-uniformity is a must if differential funding of initiatives is done based on how close projects are to stated goals. To avoid bureaucratic slow-downs, project orientation is a must. Project evaluation leaders themselves have a success based bureaucracy within the agency hidden to researchers through infrequent funding visitors who are trusted but verified. There are then two models of doing better than the market - tight study (with trusted but verified visitors) orientation and prize money. Latter is quite common for lesser goals. Both violate the equal spread political reality! India uses a third unequal strategy - event forced development (like road and homes for athletic events or border location). (Bihar argues low development as a reason!).

2. What is the risk level?

One way to argue about risks is the language used by Rumsfeld that drove most public and English grammarians to peals of laughter, when he used known-unknowns etc, being standard lingo in military. Any military unit must consider each episode as unknown force application, but the total damage expected can be estimated even though the intensity of fighting in each episode is unknown.

Applying that to aging is considered funding many places. You don't know which will work, but you can argue that some will work and the returns will justify the effort. Assuming some wastage, the funding may be uniform in the first round but not in subsequent rounds. Each effort, pending experience can be judged from similarity to California work as a start.

The ultimate work goal is instantiating of Medical Tourism for Age undo in India and in UP. It is likely nothing more than FDA approved TPE (therapeutic plasma exchange) repurposed for another benefit, likely safe and worst case, ineffective!

3. Will the funding make a difference?

Yes it will. TPE use for these purposes is novel and likely to be ineffective or too harsh for some patients. A pre-test/diagnose list can be drawn up. Aging organ age-type, also how many procedures, right NBE (I take NMN not NAD+ direct, add based on US experiences, better form, and protect NMN from liver etc)

4. How should the funding be managed?

Through funding visitors, managed internally in cost-effective manner, with rights to continue a project, reduced funding or end of project, protected from all political efforts to influence. The agency worked in the USA because not many politicians could influence the agency of Military! It is fascinating how many academicians repurposed their research to ARPA interests, BUT THAT'S WHAT VISITORS DO.

5 What difference will it make to me?

First, economically change direction not a bit, however sharing results a lot. Following detailed paper that convinced me to spend my money, and benefit from it from likely positive results, is not a science based effort but a risky engineering project which may still fail. In my judgment, the science is solid to the point of known-unknowns (engineering risk) but unknown-unknowns may still arise.

Who writes this, and why?

I am a US Citizen, India resident last 15 years, being IIT Kanpur dept. topper, glorious US experience in Research wing of Bell lab, talk to Harvard, son of illustrious Dr. Arya national disaster chief of India and UN advisor to Gujarat govt after the damaging earthquake. I have recovered some from my devastating TBI accident, work on resuscitating my quantum safe copy free encryption and defeat my aging to become youthful again, no matter the risk.

Monday, February 22, 2021

Prepare for aging procedure

Once the intellectual decision is taken, what next. Improvement by TPE (Therapeutic plasma exchange) means some questions. Consistent with our observations. This work improves our understanding of the systemic paradigms of multi-tissue rejuvenation and suggest a novel and immediate use of the FDA approved TPE for improving the health and resilience of older people.

Serious understanding on what exact risks and benefits are?

In exact, I found Conboy interview, essential reading to exact understanding of my belief. Starting 2001, I have chased SENS, of Dr Audrey de Grey. Then he was noticed as a target of MIT Kids after he claimed to be working on Long health span of 1000 years. I learned that he was no light weight, but medical head at Oxford. Computer Scientist who had changed to medicine. Then he was offering a million bucks for lengthening mouse life by 20% or more. I tracked him 20 years. His wife died (he was 10 yr younger), retired from Oxford, moved to the USA. SENS remains, his baby now, and he collects money and thus funds lifespan research over the world. In 2005, he funded doctor pair Irina and Michael at UC Berkeley, and they did the original parabiosis work and paper. He also funded the pairs work in 2020 which also include Mehdipour siblings to watch out in future. Almost every one else interpreted the original work to imply magic proteins in young blood and several doctors from Stanford and UCB formed companies to sell the magic proteins isolated from young blood and medicalized by them. Not Conboy couple who worked on alternate dilution interpretation and proved it Nov, 2020! Other than Dr. Sinclair, only Dr. de Grey gets my full attention re age. They have met and respect each other!

Listing of goals?

Health span. 20 years bioage subtraction. Best safety I can muster. Relief of non-fixable-allopathy diseases. Horvath age post procedure.

Who will be my seconds in TPE?

My father were six brothers and 2 sisters. That is 32 cousins, 12 from mother side. Several became doctors. Four maternal nieces are MD. My ex-wife was MD. She might be tempted to watch me suffer!

Deeper looks at aging?

In fact, a decade ago, a group of prominent scientists penned an open letter describing the SENS strategy as pseudoscience. Say what you will about Aubrey de Grey, but one of his greatest strengths is to challenge conventional thinking. All innovative ideas appear to be lunacy at some point. While Aubrey’s seven strategies of SENS may not all bear fruit, Dr. de Grey is overcoming the inertia that has long kept longevity science subdued. For ex. senolytic drugs have been developed and are in clinical use!

Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin

Heterochronic blood sharing rejuvenates old tissues, and most of the studies on how this works focus on young plasma, its fractions, and a few youthful systemic candidates. However, it was not formally established that young blood is necessary for this multi-tissue rejuvenation. Here, using our recently developed small animal blood exchange process, we replaced half of the plasma in mice with saline containing 5% albumin (terming it a “neutral” age blood exchange, NBE) thus diluting the plasma factors and replenishing the albumin that would be diminished if only saline was used. Our data demonstrate that a single NBE suffices to meet or exceed the rejuvenative effects of enhancing muscle repair, reducing liver adiposity and fibrosis, and increasing hippocampal neurogenesis in old mice, all the key outcomes seen after blood heterochronicity. Comparative proteomic analysis on serum from NBE, and from a similar human clinical procedure of therapeutic plasma exchange (TPE), revealed a molecular re-setting of the systemic signaling milieu, interestingly, elevating the levels of some proteins, which broadly coordinate tissue maintenance and repair and promote immune responses. Moreover, a single TPE yielded functional blood rejuvenation, abrogating the typical old serum inhibition of progenitor cell proliferation. Ectopically added albumin does not seem to be the sole determinant of such rejuvenation, and levels of albumin do not decrease with age nor are increased by NBE/TPE. A model of action (supported by a large body of published data) is that significant dilution of autoregulatory proteins that crosstalk to multiple signaling pathways (with their own feedback loops) would, through changes in gene expression, have long-lasting molecular and functional effects.