Overview 2022
My colleagues and their loved ones continue to die, no one has reported, despite their attempts to apply, cutting-edge technology. It must mean one or more of
1. Unfamiliarity with modern aging science
2. Knowledge but conscious decision to escape likely useless expense
3. Lack of belief from some kind of fatalism, luck, religion, etc.
About #3, everyone has the right to be stupid, except our civilization will advance to a state where such morons will be charged with murder of responsibility. The same applies to greedy of #2. People in #1 will be charged with negligent homicide, exactly like the accident-involved driver.
The only tolerated defense is I tried in this way (of top scientist) after reading and still failed.
Who are these top scientists and why?
Every person who argues anything not empirical is a meta-moron. All in the top list did Nobel quality work (acknowledged in the aging community by the overwhelming majority) and followed by delivering another such research.
There are only a few, found by continuous work of 20 years
The whole top field of Aging
1. Dr de Grey, for introducing/developing an engineering approach to the aging problem and senolytics
2. Dr. Sinclair, for NMN and 2019 theory of Aging
3. Dr. Yamanaka for inventing Yamanaka factors and iPSC.
4. Dr.Horvath for DNAm/GrimAge and Eutherian applicability of methylation
5. Drs. Conboys for initial heterochronic parabiosis and not young blood but plain albumin works
6. Dr. Greg Fahy for TRIIM and TRIIM-X
--------------------
Unlike. any normal human, A scientist, to me, is one who keeps his religion strictly out of the propounded theory. It can not matter what their belief system is, I only believe in empirical theory everywhere, It matters not what he divines for his beliefs from empirical theories. God is NOR dead but irrelevant to my science. This means empirical facts remain independent of their theories. You have to prove everything from empirically constructed theories. Next is personal despite excellent folks who believe otherwise, they remain meta-morons and vulnerable to sophisticated thugs exploiting their stupidity.
The aging theory has been the essential goal for 4000 years since the dawn of written language in Mesopotamia through empirical novels of Gilgamesh. Since that time many fraus have arisen. How can you decide I am not one too? Because I only state this story on empirical proofs by Dr. Sinclair at Harvard. Any mistakes are mine and will be corrected once pointed out.
How can one provide proof empirically for any theory of aging? First, you have to accept evolution. Then you demonstrate the correctness of your theory on mice, doable much faster given their small lifespan. Also, it is ethical to sacrifice mice.
The mice have their optic nerve destroyed by crushing. Next, mice in this experiment prove mice have gone blind. How in mice? Mice stare at lines. If not blind, then their throat moves their head to the side the lines move. All crushed optic nerve mice prove they have become blind, Now the NAD+ boost is done. All the mice so treated get back eye-sight after treatment. Their eyes act like genuine eyes for the rest of their life. Note that I skip over treatment which is done by triggering genes.
So aging is understood in mice. Same works in other animals. By evolution, also applies to humans. The experiment has a human analog, for whatever reason, people end up with diseased optic nerve and become blind. They can be cured with an analog NAD+ boost.
A full life of the human-animal?
A human or any sexual evolution animal starts from a single cell called a zygote that fuses the mother and father DNA halves. The DNA of the zygote divides repeatedly over the birth intervals. The DNA has an epigenomic layer that modifies the cell by context. Eventually, the birth-human is produced. It keeps growing till adulthood. This happens with a continued division of stem cells. The body is repeatedly attacked by useful microbes and pathogens. There is a full-fledged immune system for inbuilt and adaptive immunity.
Humans and similar animals have 3 classes of enzymes that control the stem cells. The stems do not wither away. They stop their growth activity as a consequence of chemical signals. They are needed badly in wound repair till death!
The classes are Sirtuins, AMPk, and mTOR Keeping them occupied is how aging will be intervened in Singularity 1.0. There are 7 Sirtuins, which only Sirt1 will be focused on. AMPk and NAD+ improvements are sought. mTOR signals abundance and increases with proteins signaling body no longer be in an alert state, shutting down repair machinery deployed for fears of starvation. This is counteracted by fasting, exercise, low sugars, low proteins, etc. These are excellent ways to fool the body which responds by hunkering down for adversity!
Roughly, NAD+ boosters (sirt1), metformin (AMPk), and low dosage rapamycin (mTOR) affect the growth genes. One has no dangers of body growth because the stem cells are halted by independent chemicals.
Very brief cell biology required to understand Aging and mRNA vaccines?
A cell has many compartments. Interest to us are
1. Nucleolus sack containing the DNA
2. zero plus mitochondria sub-cells
3. Ribosomes
How does a cell work? Two top important processes are making a protein and making energy.
To make a protein, it is somehow included as query protein, which enters the nucleolus and matches the short-chain in DNA which produces mRNA with one new sugar, enough to mark the molecule as mRNA that now exits the nucleolus. Once in the cell, it unites with a ribosome and makes the needed protein. The mRNA is still there and can not reenter the nucleolus. It dies as programmed to die quickly. Sometimes it exits the cell but is then eaten by an immune cell.
Or the signal might make energy, then ends up in a mitochondria subcell. They have their own small DNA. In any case, the signal causes production from ATP by Krebs using NAD+.
Why does NAD+ decline and what if it does?
NAD+ catalyzes many Krebs subcycles. It is basic to convert to energy, autophagy, and apoptosis. NAD+ is slowly, and with difficulty made from vitamin B3 in each cell, and is used in many sub-cycles in the Krebs cycle in so many animals and human cells. Its loss hurts by lack of energy, weakened immunity, more cancers, and many chronic diseases.
It declines because it bothers dead senescent cells which accumulate because of autophagy and apoptosis decline. To adulthood and near beyond, bad cells are garbage collected and replaced by new daughter cells from division. But that does not happen with age. The dead cells accumulate. They take to producing SASP. Some make neighbor cells senescent too. Others simply neutralize NAD+ which bothers dead cells. Each dead cell not removed is a big problem.
Hallmarks of Aging?
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contribution to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging with minimal side effects.
English Goal
Unlike. any normal human, A scientist, to me, is one who keeps his religion strictly out of the propounded theory. It can not matter what their belief system is, I only believe in empirical theory everywhere, It matters not what he divines for his beliefs from empirical theories. God is NOR dead but irrelevant to my science. This means empirical facts remain independent of their theories. You have to prove everything from empirically constructed theories. Next is personal despite excellent folks who believe otherwise, they remain meta-morons and vulnerable to sophisticated thugs exploiting their stupidity.
The aging theory has been the essential goal for 4000 years since the dawn of written language in Mesopotamia through empirical novels of Gilgamesh. Since that time many fraus have arisen. How can you decide I am not one too? Because I only state this story on empirical proofs by Dr. Sinclair at Harvard. Any mistakes are mine and will be corrected once pointed out.
How can one provide proof empirically for any theory of aging? First, you have to accept evolution. Then you demonstrate the correctness of your theory on mice, doable much faster given their small lifespan. Also, it is ethical to sacrifice mice.
The mice have their optic nerve destroyed by crushing. Next, mice in this experiment prove mice have gone blind. How in mice? Mice stare at lines. If not blind, then their throat moves their head to the side the lines move. All crushed optic nerve mice prove they have become blind, Now the NAD+ boost is done. All the mice so treated get back eye-sight after treatment. Their eyes act like genuine eyes for the rest of their life. Note that I skip over treatment which is done by triggering genes.
So aging is understood in mice. Same works in other animals. By evolution, also applies to humans. The experiment has a human analog, for whatever reason, people end up with diseased optic nerve and become blind. They can be cured with an analog NAD+ boost.
A full life of the human-animal?
A human or any sexual evolution animal starts from a single cell called a zygote that fuses the mother and father DNA halves. The DNA of the zygote divides repeatedly over the birth intervals. The DNA has an epigenomic layer that modifies the cell by context. Eventually, the birth-human is produced. It keeps growing till adulthood. This happens with a continued division of stem cells. The body is repeatedly attacked by useful microbes and pathogens. There is a full-fledged immune system for inbuilt and adaptive immunity.
Humans and similar animals have 3 classes of enzymes that control the stem cells. The stems do not wither away. They stop their growth activity as a consequence of chemical signals. They are needed badly in wound repair till death!
The classes are Sirtuins, AMPk, and mTOR Keeping them occupied is how aging will be intervened in Singularity 1.0. There are 7 Sirtuins, which only Sirt1 will be focused on. AMPk and NAD+ improvements are sought. mTOR signals abundance and increases with proteins signaling body no longer be in an alert state, shutting down repair machinery deployed for fears of starvation. This is counteracted by fasting, exercise, low sugars, low proteins, etc. These are excellent ways to fool the body which responds by hunkering down for adversity!
Roughly, NAD+ boosters (sirt1), metformin (AMPk), and low dosage rapamycin (mTOR) affect the growth genes. One has no dangers of body growth because the stem cells are halted by independent chemicals.
Very brief cell biology required to understand Aging and mRNA vaccines?
A cell has many compartments. Interest to us are
1. Nucleolus sack containing the DNA
2. zero plus mitochondria sub-cells
3. Ribosomes
How does a cell work? Two top important processes are making a protein and making energy.
To make a protein, it is somehow included as query protein, which enters the nucleolus and matches the short-chain in DNA which produces mRNA with one new sugar, enough to mark the molecule as mRNA that now exits the nucleolus. Once in the cell, it unites with a ribosome and makes the needed protein. The mRNA is still there and can not reenter the nucleolus. It dies as programmed to die quickly. Sometimes it exits the cell but is then eaten by an immune cell.
Or the signal might make energy, then ends up in a mitochondria subcell. They have their own small DNA. In any case, the signal causes production from ATP by Krebs using NAD+.
Why does NAD+ decline and what if it does?
NAD+ catalyzes many Krebs subcycles. It is basic to convert to energy, autophagy, and apoptosis. NAD+ is slowly, and with difficulty made from vitamin B3 in each cell, and is used in many sub-cycles in the Krebs cycle in so many animals and human cells. Its loss hurts by lack of energy, weakened immunity, more cancers, and many chronic diseases.
It declines because it bothers dead senescent cells which accumulate because of autophagy and apoptosis decline. To adulthood and near beyond, bad cells are garbage collected and replaced by new daughter cells from division. But that does not happen with age. The dead cells accumulate. They take to producing SASP. Some make neighbor cells senescent too. Others simply neutralize NAD+ which bothers dead cells. Each dead cell not removed is a big problem.
Hallmarks of Aging?
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contribution to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging with minimal side effects.
https://pubmed.ncbi.nlm.nih.gov/23746838/#&gid=article-figures&pid=figure-4-uid-4
-----------------------------------
I am only interested in all-win plans. Here players are consumer, doctor and me. Every thing is spelled out, anyone can raise more issues, transparently answered with question raiser identified as desired but never with email address.
Consumer wishes to reduce bio-age, starting with a physician baseline, and wishes to spend the doctor estimated money over approved duration. That is followed with treatment, updated every year. Must contact through me and pay only charges for generic information,
Doctor examine the patient and decides on whether to admit. Unadmitted consumer gets a health checkup for initial test. The doctor, on acceptance draws up initial duration, medicine protocol and delivers a free list of sellers from which the consumer can order. The win for doctor is brand new motivated patient. The doctor is only charged per new patient provided by us.
I collect seller data, patient data and feedback over province, state, and country; thus draw up the generic protocol/language for base questions and examinations. These can be modified by the doctor based on their experience and examinations and patients reports. There no known side-effects but it can not be the case forever and all histories will be analyzed and shared.
The privacy is full in that no identifying information is kept or shared. Seller lists are never given any data by us, and the sellers are limited to consumer provided data. Further security is the doctor allowing mail to their address with doctor provided identifiers for selection.
So clearly, the name and clinic address of the doctor, along with 10 text lines (A4 font-size 14) or less space will be linked to the list of doctor. The patient will be directed to requested doctor and our initial data will be emailed then. We will update every year and the patient data will not be kept on no request every year. on continue, the same information shared with doctor be also mailed, All doctors can consult with us on every age patient upto-date on annual registration. Clearly good patients must be rewarded with world experience and formulate questions on differences their doctors do.
Any such service must provide some way of bootstrap trust. I, Dr. Arya Ph.D. am a full user of my recommendations beyond public reviewable documentation and have no hidden agenda.
I have drawn up these rules based on analogy of friendship, marriage, education, etc. sites where all-win solutions are possible.
Intervention - the meat at last
---------------------
The whole reason behind the book so far is to point out the essential simplicity of aging intervention, once the science is understood, A very complex protein diagram can be drawn as this picture.
Aging is at the bottom At the top are two processes - growth hormone and calorie restriction. In singularity1.0, you will not do much better than very careful people with tight food intake and solid exercise. However, you can get benefits of calorie restriction and exercise, not by total sybarite attitude, but without paying for intermittent avoidance of calorie restriction (unnecessarily hard to be religiously honest) and exercise. Fully immobile desk sitters can not be helped but no need to run every day either.
The Dietary arm has 3 things - Sirt1, AMPk, and mTOR, learn these 3 names.
A. Sirt1 fixes are also called NAD+ boost and either by NMN or NR, strong proof that either work, even both with consumers with lots of money. I believe Dr. Sinclair who thinks NMN is better and rather than both, I would double on NMN! Liposome NMN is way more effective (I guess 4 times) so Dr. Sinclar's diet of 1gm/day is my 250 mg/day liposome. Now my add, just NAD+ boost is not enough! There are 4 holes.
1. Calcium Deposits in blood vessels lead to arthritis of some kind and some way of strengthening blood vessels as well cleaning up vessels is needed. When mib626 is ready by Dr. Sinclair, it will eliminate NMN and resveratrol. Both needed that day. Non-liposome users should prefer pterostilbene over resveratrol. This compound adds nitric oxide to vessel walls.
2. Unnecessary to eat soya foods, which can grow worse and give you vitamin K2, called a superfood in the US. I escaped Corona despite 25 years in the USA because I drank (through milk) cumin to boost immunity and 6000 IU/day of vitamin D3. Only 600 IU is needed to escape rickets. But it is a hormone and does. many other things like moving calcium to bones and reducing inflammation, Best is to find Liposome D3/K2.
3. NMN consumes methyls and for a majority of people, treats down feeling. For this purpose, TMG is needed though not as a Liposome.
4. Dr. Kennedy suggests CaAKG. It seems compatible, ask me in September how I fared. Dr. Kennedy is believed since D. Sinclair respects him and he was chief of Buck Institute for many years.
B. AMPk is fixed by Metformin, even for non-diabetics. If metformin prescription is a problem then berberine can be used.
C. mTOR fix is reverse of He=men who increase it to make muscle. For Aging you want to reduce it, All aging Doctors look thin and starving except they look longer. mTOR fix means you give up a muscle-bound or very proteinateded look. Why reduce mTOR? Lower value alerts body systems to shortage of proteins and hunkers down options to survive the shortages well. That is a great setup for anti-aging. Note that an arm from growth hormone also goes to mTOR. What is good to Age 30 (mOR boosted to great looks) is an aging disaster. No muscle-bound has crossed 100.
How can mTOR be reduced? Boosting NAD+ or AMPk fixes mTOR some. Low-dose rapamycin has clinical tests only now.
D. An obvious solution now. but not 10 years ago but for Dr. Aubrey de Grey, who actually developed senolytics, is to forcefully remove the dead cells, which happened automatically in youth and before through autophagy and apoptosis. Well-behaved dead cells display a tag and are cut up by the immune system and waste pieces are carted by kidneys. But with age, dead cells remain, with the severe consequence of SASP (hundreds of bad chemicals). SASP produces inflammation, thus causing heart problems. Senescent cells also kill their neighbors. SASP also hates NAD+ because it bothers senescent cells. All in all, SASP produces not temporary but lifelong decline. And age raises senescent cells.
Clearly senolytes not only reduce the bad effects of SASP but can even reduce the NAD+ losses and thus be NAD+ boost. SASP is too wide, contains different chemicals from the specialization of dead cells, and the NAD+ boost is iffy but required as just boosting NAD+ will fail with rising SASP. Different senolyte fix different cells. There are many senolytes, do somewhat different things and can not be replaced unless one is effective for some time.
Many senolytes meet my composing criteria, being organic or names. These are spermidine, Fisetin, apigenine and quertecin. Spermidine was first isolated from sperm but gets produced from wheat germ. There is a whole class of organics called flavonoids which are safe but useful senolytes. Once past my aging fix, I will manufacture many mixed to one which will be widely effective as senolyte!
E. Another diction of growth hormone through IGF is the insulin-like growth factor. You could go from IGF1 through FOXO bypassing mTOR. In any case, painfully learned by clinical California doctors is that igf-1 directly causes the side-effect of diabetes. What about a mix of IGF-1 and diabetes medicine DHEA in an unknown ratio! Dr. Fahy proved it possible and useful in the TRIIM trial. Then corrected shortcomings to launch TRIIM-X not yet complete’ Given the nice results in TRIIM, the -X results will have to be fairly obviously bad.
The complete domination of the aging tree is a good completeness indication to me. Arbitrary claims of aging success can be ignored despite free market abuses and real improvements will likely fall in one to the five arms A-E. E5 is based on signaling molecules and will be different. But is not in the market yet and may even compete with Yamanaka factors for singularity2.0.
Rest of pages
(tbd)One subsection of half-page to three pages on these:
B3
Niacin
NR
NMN
NAD+
NaDH
AKG
TMG
Fisetin
Spermidine
Quertecin
apigenin
Flavonoid
Resveratrol
Pterostilbene
Sirtuin
AMPk
mTOR
Cancer
FOXO
Blue zone
No comments:
Post a Comment