FAQ Aging theories

 

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The unavoidable question this raises is why are you spending untold amounts on a project that flies in the face of the basic fact of the human condition, the existential certainty of aging and death. To which the unavoidable answer is another question: Who the hell else is going to do it? Google. Can it be done with probabilistic efficacy? Yes. Are others doing it? Yes. Do you get anything for self-risk? Yes. Will you succeed if a failure? Yes. TPE will likely boost some things. Does Aging theory matter? NO! No attempt by me to build on things not derived for empiricist me.

Since I offer self as guinea-pig, safety is not the only concern. Clearly I am expecting something in the efficacy spectrum to benefit me, as I have detailed earlier. An important issue is likelihood of favorable outcome and marginal outcomes that will collectively benefit me even if the main goal is not met. Theory of Information is a new Paradigm says senolysis is similar to garbage-collection that I happen to relate to, despite what practitioners know this, will not be into aging. That is a new paradigm for senolytic drugs, selecting the goals of GC and their cleanup. There seems to be no need to recycle and reuse senescent cells, given that NBE proteins that are eliminated, are all back to their pre-NBE VALUES IN 48 HOURS (AMBAR). Multiple AMBAR procedures with week gap are fine.

I admit to being a novice in basic bio step but not in macro ideas.

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Programmed vs. Non-Programmed Aging Theory Controversy

 

What are the main scientific theories of aging? 

Aging theories fall into four main categories, programmed and non-programmed, entropy based and sudden death.

Sudden death is a quantum physics concept. Here it means telomere shortening to limit.

Entropy based theories are those that assume the growing chaos eventually has no external sink.

A programmed theory of biological aging also known as adaptive aging, active aging, or aging-by-design proposes that organisms are designed to age and have a limited life span and that aging is purposely caused or allowed by a genetic program similar to the one that controls the development and growth of an organism. According to this concept, aging is an adaptation in that it is an organism design feature that was selected by the evolution process because it benefited the organism. Because a limited life span conveys benefit, organisms can possess potentially complex evolved systems that actively regulate life span.

 

Non-programmed, also known as non-adaptive or passive aging theories contend that aging is the passive result of an organism's inability to better withstand deteriorative processes and that aging has no evolutionary purpose or benefit. Aging is a defect not a feature of an organism's design. Some non-adaptive aging theories contend that aging is an adverse side effect of some beneficial function such as reproduction or cancer prevention that aids the organism in early life at the expense of aging in later life.

 

Isn’t aging known to result from generic deteriorative processes such as oxidation, wear, or other accumulated molecular damage? 

Processes similar to those that cause gradual deterioration in machinery or exterior paint also operate in living organisms. However, it is known that living organisms possess many maintenance and repair functions that act to counteract deterioration. In addition, generic deteriorative processes cannot be the entire explanation for aging because very similar species, possessing very similar biochemistry (with presumably similar exposure to deterioration), have very different life spans. According to one programmed aging concept, the aging mechanism purposely discontinues or slows the maintenance and repair functions at a species-specific age to result in the observed species-specific life spans.

 

Isn’t programmed aging incompatible with Darwin’s theory of evolution?  Doesn’t evolution favor development of characteristics that benefit an organism’s ability to live longer and breed more? 

Yes, programmed aging is incompatible with traditional evolutionary mechanics and requires an evolutionary mechanics theory that allows for a slightly expanded definition of “benefit.”  However, a number of other observed organism characteristics also appear to conflict with classical theory. This led to development of four different types of proposed adjustments to classical evolutionary mechanics theory since 1962. These alternative theories support programmed aging. The alternatives are: group selection theories, kin selection theories, evolvability theories, and gene-centered evolutionary mechanics theories. Note that there is no scientific disagreement with the idea that evolution has occurred and that current species are descended from different earlier species. The scientific disagreement centers around details of how evolution works, the evolutionary mechanisms and processes.

 

What possible “benefit” could a purposely limited life span produce? 

Different theorists following the programmed aging concept have developed theories proposing many benefits in the following broad categories: First, that a purposely limited life span increases the chance for group survival (e.g. kin, herd, larger population, even species) and thereby reduces the chance of extinction. Second, that a limited life span enhances the ability of a species or population to evolve or adapt or allows it to adapt more rapidly to changes in its environment producing a competitive advantage. Aging or other design-imposed life span limitation is obviously adverse from the viewpoint of an individual organism. Theorists generally agree that an organism’s evolutionary need for additional life span declines following the age at which it is first capable of reproduction.

 

How do programmed aging theories compare to non-programmed theories of aging? 

Non-programmed (non-adaptive) theories (mostly developed prior to 1962) fit with classical evolutionary mechanics while programmed (adaptive) theories provide a better fit with observational evidence but require one of the newer alternative evolutionary mechanics theories. Recent observations such as “aging genes” have added to supporting empirical evidence and resulted in increased interest in programmed theories. The choice of non-programmed vs. programmed aging theory is consequently essentially a choice between believing traditional evolutionary mechanics theory against observational evidence or believing observational evidence against traditional mechanics but with the support of the newer alternative mechanics theories. There are multiple programmed aging theories that differ in detail and there are also multiple competing non-programmed theories.

 

Is programmed aging biological suicide?

 Programmed aging could be considered a form of biological suicide. However, some animals and plants die suddenly following reproduction rather than from gradual deterioration and represent more explicit instances of biological suicide. Examples include octopus, salmon, and even some mammals, the male marsupial mice. Such instances of acutely self-limited life span would also fit programmed aging theories that propose that a species-specific limited life span generally conveys benefit. Some programmed aging theorists contend that gradual aging conveys additional evolutionary benefit relative to sudden death.

 

What is the history and status of the programmed vs. non-programmed aging argument? 

At some level this controversy has existed for the 150 years since Darwin’s evolutionary mechanics theory was published in 1859. Prior to Darwin, there was no reason to suspect that life span was a characteristic whose origin differed from that of other characteristics that varied widely between species. The conflict between the survival-of-the-fittest concept and life span observations was immediately noticed following publication of Darwin's book On the Origin of Species.

 

The first formal programmed aging theory was a “programmed death” theory published in 1882 by German biologist August Weissmann. Additional formal programmed aging theories based on group selection and evolvability appeared following publication of those alternative evolutionary mechanics theories in 1962 and 1995.

 

Recently, the trend has been toward increasing scientific evidence (such as aging genes) supporting programmed aging. Concurrently, scientific confidence in traditional evolutionary mechanics has declined. However, most gerontologists and other medical researchers still believe in non-programmed (non-adaptive) aging.

 

Why should we care? 

About 75 percent of all deaths in the U.S. and other developed countries now result from age-related conditions such as cancer, heart disease, and stroke. In effect, aging is the most important cause of these diseases. Understanding the aging process is therefore essential to understanding, preventing, and treating the age-related diseases. Although highly associated with aging, these diseases kill or injure many relatively young people and are the target of much or even most medical and pharmaceutical research. Programmed aging theories suggest different and additional approaches in prevention and treatment of age-related conditions relative to non-programmed theories.

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Programmed vs. Non-Programmed Aging Theory Controversy

 

Complete non-argumentative rejuvenation theory

 

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Unlike my writings so far dominated by arguments, this is no directed at a skeptic as me, but towards the vast majority of people who want a definitive theory which might be challenged, in which case the one with better reputation is picked! Greatly but subliminal manipulated by very intelligent but all evil advertisement professionals funding all knowledge inputs. Only extreme vigilance van defeat them and there is a crying need for Consumer reports funded by low taxation on sales, given proportionally by representatives selected, at center, states and districts and tied to politics for controversy and broad way of public funding. Local supreme court may be made toothless by prohibit of public funds to anyone using private funding and by commerce illegality argument of poisoning product advertisement or by constitutional amendment in extreme legal cases.

Assumption is Sinclair Theory of information on aging is essentially correct. The fact that nature has not found any other solution to DNA break as per billion years only indicates the loveliness of the solution. First DNA can be far older since life-origin might be brought in by a rock from solar system, or a supernova explosion or might even be outside our enclosing black hole reflecting the only portal between black holes possible sent by an entropy dying civilization. But then why bother with this great research of later.

All that the theory of information says is that DNA is digital equivalent of enclosing analog epigenome, methyl groups are added and subtracted for turning genes off and on; after long time (relative to DNA processes) the methylation process fails making the cell senescent which dies to either a quiet cell or ignore apoptosis signal zombie. There is no natural way to kill these cells, a great improvement will be new senolysis drugs that will target cancers and aging causing zombie, caused by these senescent cells. Periodic cleaning is needed.

Not much is known about senolysis drugs and their cleanup. They may be specific to a particular mesenchymal or other specialized zombie. Or it may be capable of clearing many kinds of zombies. The specialization for a specific kind of organ cell may not be needed. The senolytic drug may be effective on many cancers. It might even be a generic antagonist to zombies in general, and then be a true age drug. Aging drugs are not needed to garbage-collect all zombie, as long as a significant number of zombies are reduced.

As a strange computer scientist, I am amazed at how similar this process is to garbage-collection. I know a little more, since the MIT expert who invented copying garbage-collection professor-ed in Rochester and was my faculty advisor. Just to be in good books, I learned garbage-collection and even Google 3 mark algorithm in Golang of Google and why it has taken over even Python!

In computer terms, initially the body is clean of methyl (have a lot of free storage). To adult-hood, storage is allocated and then program runs (life). As time goes by, the free storage is exhausted. Eventually, garbage collection is needed. There are many zombies intermixed with good records. A mark-sweep garbage collection is done. We know good cells (records) are those that are reachable from top registers. Here, the bad cells are those that that became zombie, like one form of PC where free cells are so marked on deletion. Biology is simple in that there is no long chain to GC, just marking on deletion is enough, Senolytic drugs kill all cells that ignore certain kind of apoptosis signals! They must not harm normal cells. If they kill many kinds of zombies then great. The only thing is NMN. Experimentally, it strengthens good guys by NAD+, boosting mitochondria. Same effects by NR or Mitoq. They may or may not strengthen a zombie. They certainly do not increase or decrease zombie populati0on, but lengthen becoming zombie, that is reducing cell age!

General theory of aging

 

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I have worked on an actionable theory of aging with an empiricist mind so far - why should I worry about how the procedure work but to work on them as black boxes, alleviating missing information and known side effects. However, I have reached the limit and I need to have a theory of aging to proceed. The first thing is to build only the needed parts. What I am thinking is remove some proteins from the plasma, and then replace it, hoping the removed proteins will extend age. I will not try this on self, test it on mice first. How? Not simple now but let us see how that is done. Assume it is done. What then? Whatever I plan has to yield testing on mice but should work on human cell or on yeast first.

Goal is protein removal machine as adjunct to TPE machine some day. Filtering will be done by adding some chemicals to the plasma drawn.

Why not work with blood direct?

I think that cells (red, White) and platelets are likely sensitive to chemicals, far more than plasma. If the filtration is done, it will likely be on plasma.

Why focus on first and why?

CD38 and apoptosis prevention boosters. Cancer cells ignore apoptosis signals. Even senescent cells. In fact, senolysis is a brand-new method to deal with cancers and may work for aging too. The reason I am not hopeful is that the signals may be cell-specific. For cancers, depending on kind, the signal may be specific. It means targeted chemotherapy is needed specific to cancers. On the other hand, many cancers can share the signal.

Does not that talk imply an aging theory?

Yes it does! While purposely ambiguous on some matters, must admit a theory application sometimes. My current theory is some antagonist pleiotropy (All evil chemicals had youth-useful purpose) NAD+ resilience (fix, not robust against). What that means is that bio-events have two parts - damage up to a maximum, period measured by robustness and recovery period of resilience.

Where do they come from?

Robustness is largely species specific. Resilience is by specified groups of species. Similar species share resilience (I assume similar to break in DNA). That is because of my belief that resilience is a much harder property to arise by evolution! The hardest stress that a cell handles is DNA break. Unfixed cells become senescent. All life have the same break fix mechanism - never invented again by nature in a billion years. That is why animals share common methylation that happens at about the same rate. It is amazing that methylations are like annual rings in trees!

Why not expect age-extension at once but after some time?

It is my deep conviction that all best current modern medicine is dealing with the specific hallmark of aging determining the chemical fixes to specific problems found in increasingly precise chemistry. Lost in the trees are forest management ideas ignored. The fixed buggy tree is better for a while and attacked by another bug. If we assume that trees have the strength to fight bugs, a better approach is while the current problems are being fixed, simultaneous effort is being made to strengthen the immunity of trees, hopefully helping in the current problem and against subsequent infestations. Now the problem referred to. There are a small finite number of resilience chemicals. Apply them all and you solve many problems. Even if you don't fix any, those present in blood flower in dilute blood and regain strength. Eventually, all the bad ones are known and can be filtered out. No regrowth is stunted by the plasma The expected regrowth is not needed. Looks like 0ne week between procedure can be reduced to next day if all the bad chemicals were known and then the filtered same plasma is used. Not clear what is sped up by a week buys? CD38 is different as it is known bad with no known good things - it arises as an evil chemical byproduct of resilience, and hence can be filtered out. Slowly the list of evil be identified but never needed,

What is the assumption in above?

We assumed that the evil chemicals did not grow-in NB but good did. That is known true for every blood protein because this assumption is needed to explain AMBAR results. None of the oldies died while the clinical trial proceeded. In fact just boosts I have in mind comes from general TPE side effects and likely not nullify anti-aging parts of TPE. Too many protein fixes might. Protein subtraction might.

Aging Motivation

 

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Where does change come from, why is Arun still a child? One answer is designing spaces with marginalized people in mind to makes them better for everyone.

 https://www.popsci.com/story/technology/curb-cut-effect-accessible-design/

IF TRULY CARRIED AWAY, 2030 IS HUGE

https://money.cnn.com/2015/06/03/technology/ray-kurzweil-predictions/index.html

Today is a change,First what caught my fancy.

https://www.youtube.com/watch?v=IEz1P4i1P7s

Why is all kinds of knowledge needed, is clear from this introduces CD38 I mentioned.

https://www.lifespan.io/news/the-intertwined-nature-of-nad-cd38-and-senescence/?mc_cid=3f733ddbf5&mc_eid=d889cad40c\

Then if you wantNMN.

https://www.youtube.com/watch?v=bUAN1Y3gFm4&feature=youtu.be

Last but is you want to join me

https://aaqg-arunarya.blogspot.com/2020/11/a-new-kind-of-startup-aastartup.html

I had a long conversation with a salesperson of uthever in China. They are ready to sell me NMN for $1600/kg. That is better than best, if I can solve transportation and customs (solved). 1 kilo is for 3 people per year. 500 gm just for me is enough under $1000. I can exceed Dr. Sinclair but might need only 500 mg/day since taking by IV. My mother and wife await my doing the procedure first, no help from them.

Diseases of Aging - Induced by time

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It is not my intention to act as doctor, my knowledge is deep in very few areas of interest to me. However, certain broad area have to interned at very shallow level and these are likely to be of interest to some. Aging, understood as a universal chemical process and interventions to increase the health span, is one of the areas. Let us examine two very major diseases here - Parkinson and Alzheimer's. These are considered nonintervention, if you or loved have it then the best is to reduce the evil consequences as much possible.  But, TPE intervention makes sense in Alzheimer's. AMBAR is very cutting edge, and surprise is that the equipment is available in Delhi, due to unthinking but political move of AAP to battle Corona, made unused for NBE with cured patients, but the vaccines are unexpectedly here and usable. Means TPE is there, can be repurposed for fighting aging, a very useful disease with no recognition as one by FDA! I was amused to learn that Dr. DobriKirprov is the first doctor in the USA entitled to specialist status in TPE! The AMBAR project is old and in fact Drs. Conboy did the lessened recovery interpretation of their classic 2005 surgical hetero chronic blood exchange paper, in 1916 when funded by none other than Dr. de Grey. Naturally, Dr. Kirprov was coauthor in 1916 and also in 1920!

The blood-brain-barrier or BBB seems to defeat all improvements to brain, independent to blood. That (improvements) is a consequence of two new facts, even today not known to middle-aged Doctors in India who were taught by senior Doctors. First there is old age neurogenesis in hypothalamus, essential for short to medium term memory. Decline in neurogenesis is why all old people decline in fresh memories even though they can remember old things! The second fact is that the ratio of beta-amyloid in blood and brain is a constant. This is maintained by some beta-amyloid moving from the brain to diluted blood (where it unites with albumin). You see that aged brains show distinct beta-amyloid patches, essential to Alzheimer's! AMBAR shows that. Twin improvements in memory and reduced loss of sanity was objectively measured and showed 50-60% improvement! I attribute lack of world-wide processing as partly poor information spread and partly lack of TPE equipment.

Stupidity of doctors' about plasmapheresis, indicates a very wide open entrepreneur area with unused TPE equipment making TPE lot cheaper, hence applicable here - patient supply huge if improved self. Precisely sensible gamble, worst is no effect and minor pain! Low cost advertise-strategy will work here initially, with likely a huge wall of disincentives to overcome later. Self TPE is likely the smartest move in my life! Glutathione is a likely add to my NBE. If small lightened, will become walking ad proof! Since I intend life long NMN by IV, adding Glutathione will be trivial.

Parkinson is caused by loss of doipamine. It is fixed differently. Taget is mPTP described next which converts autphagy process to destructive. The activity of the mitochondrial permeability transition pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging reactive oxygen species, Ca²⁺ and NAD⁺. The various pathways that control the channel activity, directly or indirectly, can therefore either inhibit or accelerate aging or retard or enhance the progression of aging-driven degenerative diseases and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles, protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. The increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.

Since CD38 is bad too, CD38-in-78C is a potent suppressor, in turn raising NAD+. No one seems to know why not used commonly. The Intertwined Nature of NAD+, CD38, and Senescence is missed.

If rapamycin strikes your fancy, please read this.

Design of Self-TPE

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So far 

www.aging‐us.com AGING 2020, Vol. 12, Advance
Priority Research Paper
Rejuvenation of three germ layers tissues by exchanging old blood
plasma with saline‐albumin
Melod Mehdipour1, Colin Skinner1,*, Nathan Wong1,*, Michael Lieb1,*, Chao Liu1, Jessy Etienne1,
Cameron Kato1, Dobri Kiprov2, Michael J. Conboy1, Irina M. Conboy1
1Department of Bioengineering and QB3, UC Berkeley, Berkeley, CA 94720, USA
2California Pacific Medical Center, Apheresis Care Group, San‐Francisco, CA 94115, USA
*Equal contribution
Correspondence to: Irina M. Conboy; email: iconboy@berkeley.edu
Keywords: blood exchange, therapeutic plasma exchange, multi‐tissue rejuvenation, rejuvenation by dilution
Received: May 13, 2020 Accepted: May 20, 2020 Published: May 30, 2020
Copyright: Mehdipour et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution
License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.

A lot of my doubts vanished when I encountered peer-reviewed government reference here.

Once TPE is decided, the next issue is replacement plasma. Since I am volunteering and paying for the procedure, I am entitled to design of replacement plasma, in consultation with the doctor who will vet it on me. Basically I am open to dangers, but not to "not done yet". My own choices have to be motivated by advantages for me.

Let us look at what I want

1. Saline, to provide for bulk. Solves Metabolic alkalosis.

2. Albumin, at concentration in blood. It is a neutral tie-in for all proteins being removed, otherwise neutral to aging, Read: experimented with mice by Conboy and Humans in AMBAR. An albumin saline solution seems to be all needed for plasma lost, buttresses by cells, platelets etc, saved and restored in plasma. Albumin is not just neutral, but AMBAR may be interpreted as setting up a fixed ratio between beta-amyloid in brain CSF and blood, and loss of it in the brain to increment in blood to form albumin binding. It is this loss that produces improvements to Alzheimer's patients, despite BBB! Several procedures are needed for cleaning to significant levels, in AMBAR was weekly six times, then monthly for 6 months. Schedule may be smaller for an age/severity-early patient as me. TPE must be, and is, free of side effects beyond tiredness, but significantly donor facts, missing in my case.

3. NMN to protect it from the liver. Special NMN needed might reach me mid-March. Much better results are expected than sub-lingual methods used. I plan of weekly NMN IV for rest of life at $1000 per year unless I venture to make it in India or convince Ramdev etc to make it, for if it works for me, many customers as me will need it. If forced into manufacture or administration, IV can be extended to other similar products as NMN.

A gradual increase in CD38 has been implicated in the decline of NAD+ with age. CD38 inhibitors may be used as therapeutics for the treatment of asthma. CD38 has been used as a prognostic marker in leukemia. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are NAD+ precursors, but when NR or NMN are administered, CD38 can degrade these precursors before they can enter cells. Diluting blood to half CD 38, is likely to help in NMN by IV.

4. Calcium, at concentration in blood (how=TBD) to avoid one side effect seen from TPE. Solves hypocalcaemia.

5. Potassium, at concentration in blood (how=TBD) to avoid one side effect seen from TPE. Solves hypokalemia.

6. ... Others to be considered like some antibiotic. Pterostilbene is a general purpose broad spectrum antibiotic used by plants for invaders. Its chemical relative, resveratrol, received FDA GRAS status in 2007,[9] and approval of synthetic resveratrol as a safe compound by the European Food Safety Authority (EFSA) in 2016. Pterostilbene differs from resveratrol by exhibiting increased bioavailability (80% compared to 20% in resveratrol) due to the presence of two methoxy groups which cause it to exhibit increased lipophilic and oral absorption.[5] Might Solve decreased immunity. Need it as companion to NMN anyway.

What if this NBE fails?

There seems to be no gerolavic reasons to K and Ca increment, but you never know! In any case, NMN by IV will improve! The exact recipe will not be disclosed but becomes a strong product for replacement plasma. I will seek funding to develop replacement plasma service if it works on me, in this or subsequent efforts' inline with self-sufficient India and a very major export to the entire world, open  to any proven solution. There is no established solution to aging, or even a candidate in trial. Only Dr Kirprov in San Francisco may be a competitor, but AMA/FDA delays will make him toothless for a while. What works on me will promise a fast FSSAI valid deserving clinical test. Sir Modi understands bureaucracy.

Is old plasma of any use?

Yes !! In many small volumes, it can be used in many experiments to pin-point the bad proteins and their removal so that eventually the plasma can be cleaned and reused without diluting it! Interesting but true, it can be added to mice-plasma!

 

 Philosophy

As someone taking the risks, I am entitled, as a non-medical scientist, of brief descriptions of my philosophy. I believe in natural evolution, rational scientific speculation, no-God and nonspiritual nature. Thus aging is simply chemistry, interesting as applicable to all mammals extending to a few hundred years as opposed to trees of a few thousand years and potentially unlimited for some reincarnating jelly fishes escaping predation. The higher end mammals survive being top predators and beating cancers. True hibernation may never happen to humans, but resuscitating intervals of up to 100 years are possible by slowing organ human processes and direct external blood processing. That claims of post-death resuscitation are pure sci-fi, not rational scientific speculation is my basis of declaration of post-death cures for killer diseases, a folly view and proud dedication of all my organs post-death in the USA or here (needs dual freeing) to reuse (here you have to pay!).

Two  bad guys in aging are mitochondrial permeability transition pore, mPTP and cluster of differentiation CD38. It will be interesting to see if TPE machine can be modified to filter them out with positive anti-aging effect.

Antagonistic Pleiotropy Theory of Aging is my belief i.e. the bad processes were once good, but changed with aging to become bad. Cellular senescence is a simple way of attracting immune system cells to "bad" chemicals in some cases! For one, you can't fix a problem by sheer elimination of villain chemicals - you have to reduce their effects. But I expect the problem to be as hard as management of wild life with many counter-intuitive blind alleys and strange unintended consequences! It essentially means low-hanging fruit for like 20-60 years and then a wall.

Joining all the threads

 

The Latest link

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