Tuesday, June 16, 2020

The addiction: Heroin or anti-oxidant


mea culpa. International emfubar capitalists spread a web around me using slyly bought doctors causing significant money damage to me in the past! Ros or reactive oxygen series is usefully suppressed in some but harmfully in other cases. Using quote from the Grand master <Through the 1970s and 1980s, Harman and hundreds of other researchers
tested whether antioxidants would extend the lifespan of animals. FALSE. If old habits die hard, the free-radical idea is heroin. The theory was overturned
by scientists within the cloisters of my field more than a decade ago, yet it is still
widely perpetuated by purveyors of pills and drinks, who fuel a $3 billion global
industry. Arlan Richardson and Holly Van Remmen spent about a decade at the
University of Texas at San Antonio testing if increasing free-radical damage or
mutations in mice led to aging; it didn’t.>

I wish this research was published three years ago. Would have saved me lot of money and stupid belief. NMN was ok since it was anti-oxidant. so was coQ10 and even mitoQ. You took for free radicals. Even if I was not suffering a disease, anti-oxidants improved my age!


Mortality in Randomized Trials of Antioxidant Supplements for Primary an d Secondary Prevention: Systematic Review and Meta-Analysis  https://pubmed.ncbi.nlm.nih.gov/17327526/

As for chem-blind nothing like rapamycin, good in infrequent small doses only for higher or frequent doses hurt kidney.damage to ventilator


Now a strong advice, severely effected covid patients, must be given iv resveratrol since damage to ventilator-bound-patient's lungs is not by Covid but cytotkine storm.For long life, resveratrol supplementation has known no evil side-effects and relaxes cytokine by sirt1!

Overexpression of SIRT1 Protects Pancreatic Beta-Cells Against Cytokine Toxicity by Suppressing the Nuclear factor-kappaB Signaling Pathway  https://pubmed.ncbi.nlm.nih.gov/19008341/

Note that resveratrol can be safely added to ordered drugs


Saturday, June 13, 2020

How does Sinclair apply to me

https://blazepress.com/.image/c_fit,h_600,w_600/MTI4OTg1NjQyNTk1MDUzNTM4/self-portrait.jpg

I finished long deliberations 3 days ago. It started with what does proof mean to me. Did David Sinclair meet the burden? He does. Mine thinking is very American! Any support by experience or dead tomes is wrong! There must be repeatable empirical proof in a scientist set conditions, or dependable claim done before other scientists i.e. rational skepticism. Did Dr. Sinclair meet the burden. Experimentally, he did.

But a scientific theory is more - it must be consistent to all physics, chemistry and bio-chemistry so far. It is. Being biological, it must have a believable narrative. David meets the burden fully. Narrative is consistent to evolution - explain all aging (plants bacteria, animals) since all DNA that survives, has the exclusion gene! AMPK, mTOR and Sirutins are simply exclusion gene in mammals. The theory is different enough to label any is-same emfubar historian sub animal.

Beyond being right, what are the reco and why? David talks of improving things for exclusion genes by hormesis (vaccination, Hormesis - Wikipedia  https://en.wikipedia.org/wiki/Hormesis). The theory makes lot of sense to me as it is like Talib! He has analyzed many systems as airplanes and improvements by accidents and uses it in gym. (Talib is a superman like Sinclair is). What a merger.

Meaningfully, for aging, Sinclair advises to be hungry and fasting, to turn on natural preventive circuits in me,  but unlike religious nuts, has no problems with unlimited stuffing when eating. What is more, honest enough to reject multi-day fasts as too hard and not needed. This is very hard for me as diabetic. In my case, each meal is small and there are 3 intermediate meals ( biscuits, fruits and tea) to do slow but continuous nutrition. So protein were moved to breakfast, evening meal is lauki and small chapati, have eliminated night snacks. will do it for a month. Getting up hungry after 3 days. No evil effects so far. Havn't really reduced foods, only rescheduled. Worked so far. Maybe feel or look better in 31 days. If so then  epiClock measurements before and after next month. I am spending 12 straight hours between foods. Incidentally, I do walk 1km in morn and another at evening. Covid has shut the gym and in market for like bull worker. This is self-experimentation with results shared. Best is likely less age look and no decrease in energy.

Friday, June 12, 2020

Aging proofs, digilog, how


Motivate this read

A question every intelligent reader should ask: why is theory of Information right, conflicting with EVERY idiot of the past. Why is arun arya digilog right and why does it exist? Correctness of theory of information is discussed here. Digilog is a strict subset and is right if extended theory is. It exists because the purpose of this research has nothing to do with Ageing, rather amelioration of ageing for long healthy life. Dr. Sinclair recommends things which will add 20-30 years of healthy life. There are other things in works which will add another 20-30 years and 50 years even enable thousand years! Time enough to reach wish-death. Remember Thinfo; earthian DNA has exclusion of reproduction and repair in DNA. Nothing is lost in DNA with age, it is all in the epigenome. An epi-clock can reliably predict age remaining - every moron's idea of age-extension can be numerically tested!

Proof experiment

To prove that [Theory of Information], we needed to break some mouse DNA. [easy  by shear, chemo, x-ray etc] [precise] To do that, we got our hands on a gene similar to Cas9, the CRISPR gene-editing tool. from a gooey yellow slime mold called Physarumpolycephalum, which literally means “many-headed slime.” Most scientists believe that this gene, called I-PpoI, is a parasite that serves only to copy itself. When it cuts the slime mold genome, another copy of I-PpoI is inserted. It is the epitome of a selfish gene. cuts DNA at just a few places in the mouse genome, and there is no copying process. [I-PpoI cuts at random] Instead, the cell has no problem pasting the DNA strands back together, leaving no mutations, which is exactly what we were looking for to engage the survival circuit and distract the sirtuins.

To create a mouse to test the information theory, we inserted I-PpoI into a circular DNA molecule called a plasmid, along with all the regulatory DNA elements needed to control the gene, and then inserted that DNA into the genome of a mouse embryonic stem cell line we were culturing in plastic dishes in the lab. We then injected the genetically modified stem cells into a 90-cell mouse embryo called a blastocyst, implanted it into a female mouse’s uterus, and waited about twenty days for a baby mouse to show up. This all sounds complicated, but it’s not. After some training, a college student can do it. It’s such a commodity these days, you can even order a mouse out of a catalog or pay a company to make you one to your specifications.

The baby mice were born perfectly normal, as expected, since the cutting enzyme was switched off at that stage. We called them affectionately “ICE mice,” ICE standing for “Inducible Changes to the Epigenome.” nothing different about these mice until we feed them a low dose of tamoxifen. This is an estrogen blocker that is normally used to treat human cancers, but in this case, we’d engineered the mouse so that tamoxifen would turn on the I-PpoI gene.


The mice might have died. They might have grown tumors. Or they might have been perfectly fine, no worse off than if they’d received a dental X-ray. Nobody had ever done this before in a mouse, so we didn’t know. But if our hypothesis about epigenetic instability and aging was correct, the tamoxifen would work like the potion that Fred and George Weasley used to age themselves in Harry Potter and the Goblet of Fire. And it worked. Like wizardry, it did.

[ Having been prof. myself, the juiciest experiment is when a PHD scholar experiments with many possible outcome, does one correct only by his theory. This is one, demolishing ALL religions and theories of the past.]

Fun Anecdote

[After a few months, David vacations Australia, gets call from excited lab lady] I asked her to text me a photo of the [sick] mouse she was talking about. When the photo came over my phone, I couldn’t help but laugh. “That’s not a sick mouse,” I replied. “That’s an old mouse.” “David,” she said, “I think you’re mistaken. It says here that it’s the sister of these other mice in the cage, and they’re perfectly normal.”
A tamoxifen-triggered ICE mouse at the same age has  thinning, graying hair, a bent spine, paper-thin ears, and cloudy eyes. [i.e selective aging can happen. Human id-twins share only 10-25% similarity in fate and age]

[ This one of the tests. Collectively, David meets my standards of Proof. Theory is not important. When docs can, aging will be fixed. But you need to survive till 2030! That it generates trust in Dr. Sinclair advice is crucial - plenty of sub animals who have bad advice based on gym, dead-rishi farts, medicine, experience etc. Apart from incorporation of his ideas in my routine, critical is accuracy of Horvath and epiClock, only way to  conduct aging experiments on self! I only accept empirical proof, all based on tomes of dead rishi or soothsayer are stupid! They are belief of others, but never me.]

Healthy life-extension

Dr. Sinclair extensions (aped by me in reality) are based on  evolution. Nothing (big) follows from correct theory of aging but a major idea - we do keep birth-time-record in DNA of the derivation from parents as in womb. THERE IS STILL REMOVING+RENEWING OLD EPI-GENOME! Unless a cool method achieves that by pill course, evolution ideas unlikely to spread as they need fasting (real), exercise and hot/cold. Can a non-sinclair way be found? Is it statistically independent of Sinclair to allow add?

Breakthrough Gene Therapy Clinical Trial is the World's First That Aims to Reverse 20 Years of Aging in Humans

Yes! Explains digilog. Dr. Yamanaka developed 4 factors that remove all epigenome using Cas-9 of CRISPR. NOBEL 2012. But removing all epi-genome reverts the cell back to womb state. Doing it to an organism gives you largest cancer! Amazingly, even Estee-lauder type fashion company keep scientists who applied  similar ideas on skin!

First hint that body's 'biological age' can be reversed - Nature

Now comes Nature's magic gift to humans - just halving the concentration of 3 factor's selected, is enough to control loss before cancer comes! A Stanford team, led by Tapash Jay Sarkar, Dr. Thomas A. Rando and Vittorio Sebastiano, say their method, designed to reverse these errors and walk back the cells to their youthful state, does indeed restore the cells’ vigor and eliminate signs of aging.They described their technique as “a significant step toward the goal of reversing cellular aging” and could produce therapies “for aging and aging-related diseases.”  This was 2018. Action has moved to California!

So Boston is Sinclair. Japan is Yamanaka. California is Arun Arya amelioration.

Tuesday, June 9, 2020

Aging: A study of Dr. Sinclair, current Darwin, aging theory of information




Digilog - new paradigm shift in Aging
https://aaqg-arunarya.blogspot.com/2020/06/digilog-new-paradigm-shift-in-aging.html

--------------------------------------------------------------------------------------------------------------
Do you want to understand Dr. Sinclair as a human?

Excerpts and reactions from lifespan by Sinclair 1
https://aaqg-arunarya.blogspot.com/2020/06/excerpts-and-reactions-from-lifespan-by.html

------------------------------------------------------------------------------------------------------------------
If you want to understand Digilog in Dr. Sinclair  words?

Excerpts and reactions from lifespan by Sinclair 2
https://aaqg-arunarya.blogspot.com/2020/06/excerpts-and-reactions-from-lifespan-by_8.html

------------------------------------------------------------------------------------------------------------------
why bother with a DNA clock?

1 Surprising predictor of death
2 same accross tissues , fluids, animals
3 Predicts aging

DNA clock
https://aaqg-arunarya.blogspot.com/2020/06/dna-clock.htm
------------------------------------------------------------------------------------------------------------------
Why  go to epiClock or epigenetic clock?

EPI-GENOME AND dna ARE BOTH METHYL MARKED WITH TIME. DNA is fixed at womb life., epiDNA is not.

1 It is a litle bit more accurate
2 It is, from Digilog, a way to transmit genetic information not bound by evolution, has methyl markers
3 may be the foundation of a new civization

Epiclock - Epigenetic weltanschauung
https://aaqg-arunarya.blogspot.com/2020/06/epiclock-epigenetic-weltanschauung.html

------------------------------------------------------------------------------------------------------------------
What is Digilog in your words?

What do past studies say about age and memory?


https://aaqg-arunarya.blogspot.com/2020/06/digilog-arya-understanding-of-new.html

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

I am interested in rational-skeptic reco for things I can do and measure to plan and to get feedback

How does it all effect Aging?
https://aaqg-arunarya.blogspot.com/2020/06/how-does-it-all-effect-aging.html

How does it all effect Aging?



It is my belief there are no MD followers of digilog. BY not inventing something like it,
they hurt their own prospects. NOW I consider Digilog as theory of information applied to WIDESPREAD affliction of ageing. Since ageing is an affliction, not a disease, it follows that I can order chemicals without effecting MD who can, and correctly, pursue allopathic DISEASES. It is the birth of new art of medicine like naturopathy, for a condition definitely not a disease, or recognized as one.

semantics: All terms used by MD in allopathic contexts must be added with ageing- as an adjective, whether explicitly there or not, unless the add leads to a contradiction. Thus I talk of ageing-disease, ageing-chemicals and ageing-medicine, said to be pointless in current medicine and modern allopathy as being meaningless.

ALL chemicals used must have explicit GRAS status, or a defend able narrative in recognized culture, or mode of medicine recognized by government of India. The goal is re purpose and not invent. Extreme care is needed since all compounds, natural or artificial, are chemicals. Water is Di hydrogen oxide, probably not GRAS, but defend able so.

Dr. Sinclair is often careful in prescribing chemicals since not an MD. But he has developed a wonderful way around - he will only disclose doses and frequency of the chemicals he uses and convinces his family to use. This is always legal and quite useful, except that the amounts and frequency are not settable by the consumer. It also leads to abuse by supplement manufacturers. For example, he has, in videos seen, stated 1 gm of nmn and 1 gm of resveratrol per day. Also unknown amount of metformin. Problem is semi-honest supplement makers who sell 50 mg of capsules - the dishonest/honest idea is it is nmn! Another is admixtures of uninformed chemicals with glowing approval letters. It is acceptable in free capitalism, buyer beware. But smart consumers will use their tax dollars to construct another agency like FDA to implement supplement control. Its can be international,with my favorite form of democracy - a country has votes proportional to its share in costs.

----------------------------------------------------------------------------------------------------
All excerp from great book by Dr. Sinclair

Up until the second half of the twentieth century, it was generally accepted
that organisms grow old and die “for the good of the species".

In the 1950s, the concept of “group selection” in evolution was going out of style, prompting three evolutionary biologists, J. B. S. Haldane, Peter B. Medawar,
and George C. Williams. When it comes to longevity, they agreed, individuals look out for themselves driven by their selfish genes. (In some cases, however, they press on
too much, as Dr. Sinclair great-grandfather Miklos Vitez, a Hungarian screenwriter
proved to his bride forty-five years his junior on their wedding night.)  The trio of
biologists argued that we experience aging because the forces of natural selection
required to build a robust body may be strong when we are 18 but decline rapidly
once we hit 40 because by then we’ve likely replicated our selfish genes in
sufficient measure to ensure their survival. One of trio Medawar, who had a penchant for verbiage, expounded on a nuanced theory called “antagonistic pleiotropy.” Put simply, it says genes that help us reproduce when we are young don’t just become less helpful as we age, they can actually come back to bite us when we are old.

Twenty years later, Thomas Kirkwood at Newcastle University framed the
question of why we age in terms of an organism’s available resources. Known as
the “Disposable Soma Hypothesis,” it is based on the fact that there are always
limited resources available to species—energy, nutrients, water. Kirkwood’s theory is best illustrated by fictitious but potentially real-life
examples. Imagine you are a small rodent that is likely to be picked off by a bird of
prey. Because of this, you’ll need to pass down your genetic material quickly, as
did your parents and their parents before them. Kirkwood’s hypothesis explains why a mouse lives 3 years while some birds can
live to 100. It also quite elegantly explains why the American chameleon lizard,
Anolis carolinensis, is evolving a longer lifespan as we speak, having found itself a
few decades ago on remote Japanese islands without predators.

Having capitalized on its relatively large brain and a thriving civilization to
overcome the unfortunate hand that evolution dealt it—weak limbs, sensitivity to
cold, poor sense of smell, and eyes that see well only in daylight and in the visible
spectrum—this highly unusual species ( Homo sapien = human) continues to innovate.

Wilbur and Orville Wright could never have built a flying machine without a
knowledge of airflow and negative pressure and a wind tunnel (Why all the so called inventions of Ramayana etc are fiction). In the same way, if we are to make real progress in the effort to alleviate the suffering that comes with aging, what is needed is a unified explanation for why we age, not just at the evolutionary level but at the fundamental level. But explaining aging at a fundamental level is no easy task. It will have to satisfy all known laws of physics and all rules of chemistry and be consistent with centuries of biological observations. One hypothesis, proposed independently by Peter Medawar (Nobel immunologist) and Leo Szilard (physicist, nuclear weapons)
was that aging is caused by DNA damage and a resulting loss of genetic
information.

The idea that mutation accumulation causes aging was embraced by scientists
and the public alike in the 1950s and 1960s, at a time when the effects of radiation
on human DNA were on a lot of people’s minds. But although we know with
great certainty that radiation can cause all sorts of problems in our cells, it causes
only a subset of the signs and symptoms we observe during aging,10 so it cannot
serve as a universal theory.

In 1963, the British biologist Leslie Orgel threw his hat into the ring with his
“Error Catastrophe Hypothesis,” which postulated that mistakes made during the
DNA-copying process lead to mutations in genes, including those needed to make
the protein machinery that copies DNA.

Around the same time that Szilard was focusing on radiation, Denham
Harman, a chemist at Shell Oil, was also thinking atomically, albeit in a different
way. After taking time off to finish medical school at Stanford University, he
came up with the “Free Radical Theory of Aging,” which blames aging on
unpaired electrons that whiz around within cells, damaging DNA through
oxidation, especially in mitochondria, because that is where most free radicals are
generated.

Through the 1970s and 1980s, Harman and hundreds of other researchers
tested whether antioxidants would extend the lifespan of animals. FALSE. If old habits die hard, the free-radical idea is heroin. The theory was overturned
by scientists within the cloisters of my field more than a decade ago, yet it is still
widely perpetuated by purveyors of pills and drinks, who fuel a $3 billion global
industry. Arlan Richardson and Holly Van Remmen spent about a decade at the
University of Texas at San Antonio testing if increasing free-radical damage or
mutations in mice led to aging; it didn’t.

Ironically, it was Szilard, in 1960, who initiated the demise of his own theory
by figuring out to how to clone a human cell. Cloning gives us the answer as to
whether or not mutations cause aging. If old cells had indeed lost crucial genetic
information and this was the cause of aging, we shouldn’t be able to clone new
animals from older individuals. Clones would be born old.

Yes, it’s true that Dolly, the first cloned sheep,  lived only half a normal lifespan and died of a progressive lung disease. But extensive analysis of her remains showed no sign of premature aging..

It’s certainly no dishonor to those brilliant researchers that their theories
haven’t withstood the test of time. That’s what happens to most science, and
perhaps all of it eventually. In The Structure o f Scientific Revolutions, Thomas
Kuhn noted that scientific discovery is never complete; it goes through predictable
stages of evolution. When a theory succeeds at explaining previously
unexplainable observations about the world, it becomes a tool that scientists can
use to discover even more.

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

Why We Age and Why We Don't Have To | David Sinclair | Talks at Google

627,973 views
Oct 10, 2019
https://www.youtube.com/watch?v=9nXop2lLDa4
 
belive it or not, the speaker is 50+.
In this more nuanced view, aging and the diseases that come with it are the
result of multiple “hallmarks” of aging:

• Genomic instability caused by DNA damage
• Attrition of the protective chromosomal end caps, the telomeres
• Alterations to the epigenome that controls which genes are turned on and off
• Loss of healthy protein maintenance, known as proteostasis
• Deregulated nutrient sensing caused by metabolic changes
• Mitochondrial dysfunction
• Accumulation of senescent zombie like cells that inflame healthy cells
• Exhaustion of stem cellslam
• Altered intercellular communication and the production of infmatory molecules

Fixing each increases life, all gives you immortality. It is amazing that ALL have a common source !!!!!!!!!!!

Above the biology level, and before black box level, is anatomical chemistry. Remember from biology we know

1.There are genes to control replication of cells and fix broken DNA
2. Evolution provides great advantage to DNA where these two functions are by same gene
3. repairs if off, replication when on
4. All DNA today is so, means universal ageing theory
5. Same gene means automatic exclusion. No exclusionary genes!

Humans have three category of fix protein generators: AMPK, mTOR and Sirutins. Sirutins number sir1 to sir7 and are benefited by resveratrol and nmn. Metformin acts on AMPK and is a Diabetes prescribed drug, 1gm/day tested by Dr. Sinclair for aging, very safe for non-diabetics. Rapamycin acts on mTOR and is toxic to humans. The key molecule nmn targets NAD+, same as in Krebs cycle. The key activity is in mitochondria inside a cell. Direct NAD+ or NMN wont pass into the cell. Both have to be protected from liver. Sublingual use is one way. Intravenous iv route is another. Both ways protect from liver.

The metabolic control enzyme is known as AMPK, which
evolved to respond to low energy levels. TOR is called mTOR in mammals—in every organism in which they’ve looked for it.
Like that of sirtuins, mTOR activity is exquisitely regulated by nutrients. And like
the sirtuins, mTOR can signal cells in stress to hunker down and improve survival
by boosting such activities as DNA repair, reducing inflammation caused by
senescent cells, and, perhaps its most important function, digesting old proteins.


One step before nmn is nr, so that can be used, but expensive from a patent held by chromadex. It has been found that blood nmn or NAD+ cross cell walls by becoming nr for a while! These two are expensive anyway!

So ONLY Dr. Sinclair for aging are 1gm each of Resveratrol, nmn and metformin. Right Dose - have no doctor to advise you. He has no economic concerns being a billionaire. Wrong doses of any chemical above are no good and may have  bad effects with no benefits.  Best advice by me is - talk to a doctor, show him my writings and get a prescription for 1000mg (ie 1gm) metformin per day even if not a diabetic.

I am diabetic, separate dose for ageing is bad idea, have tried NR, NAD+ and NMN for 1 year each, saw no benefits except in diabetes, which could be from acarbose after maxing out metformin. NMN must be taken with a methyl donor - 1gm b15. Don't go trying, except on good chemistry as typical doctors, even specialists know nothing about ageing drugs! The metformin advised is supported by every Aging doctor, there is nothing else in common. Personally will try iv route NMN and NAD+, but so far have not found any one selling iv forms, not stupid to form powder solution, distrust Chinese on Alibaba, cant order through pharmacists as not-MD, and still have not convinced any MBBS to prescribe.

DNA clock



Horvath clock

Chain of Methyl groups on DNA has been found very correlated with number of years before death accurate in plants, animals and people after AI models on populations. They are different in epigenomes and DNA. The epigenetic version is, said by Digilog believers as me, to be caused by aging, more accurate and a very good predictor of any claims by anyone! Amazon India used to do tests before Covid but has paused. Will someone find who does now?
----------------------------------------------------------------------------------------------------------------
DNA Methylation-Based Biomarkers and the Epigenetic Clock Theory of Ageing

Abstract

Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course. Epigenetic biomarkers may help to address long-standing questions in many fields, including the central question: why do we age?
----------------------------------------------------------------------------------------------------------------
It is possible to scientifically measure effects on life. Mobile radiation has NO effect, proponents can be reliably called subhuman.

Premature aging induced by radiation exhibits pro-atherosclerotic effects mediated by epigenetic activation of CD44 expression.

Lowe D, Raj K. Aging Cell. 2014 Oct;13(5):900-10. doi: 10.1111/acel.12253. Epub 2014 Jul 25. PMID: 25059316 Free PMC article.
----------------------------------------------------------------------------------------------------------------
Rapamycin is a toxic anti aging drug. One cannot hower use it to cheat because it is toxic and is an anti-aging chemical.

Rapamycin Retards Epigenetic Age in
g of Keratinocytes Independently of Its Effects on Replicative ,Senescence Proliferation and Differentiation

 Abstract

The advent of epigenetic clocks has prompted questions about the place of epigenetic ageing within the current understanding of ageing biology. It was hitherto unclear whether epigenetic ageing represents a distinct mode of ageing or a manifestation of a known characteristic of ageing. We report here that epigenetic ageing is not affected by replicative senescence, telomere length, somatic cell differentiation, cellular proliferation rate or frequency. It is instead retarded by rapamycin, the potent inhibitor of the mTOR complex which governs many pathways relating to cellular metabolism. Rapamycin, however, is also an effective inhibitor of cellular senescence. Hence cellular metabolism underlies two independent arms of ageing - cellular senescence and epigenetic ageing. The demonstration that a compound that targets metabolism can slow epigenetic ageing provides a long-awaited point-of-entry into elucidating the molecular pathways that underpin the latter. Lastly, we report here an in vitro assay, validated in humans, that recapitulates human epigenetic ageing that can be used to investigate and identify potential interventions that can inhibit or retard it.

digilog - arya understanding of new Darwin for eternal life


Self link https://aaqg-arunarya.blogspot.com/2020/06/digilog-arya-understanding-of-new.html for latest.

The new Darwin is David Sinclair, first MIT then Harvard for 20 years, discoverer of resveratrol., billionaire from it, NASA chosen for health of first US astronauts to Mars, founder of the information theory of ageing and thorough gentleman like Elon Musk, open to non scientists.

Digilog is Sinclair information theory of ageing in 2020. All errors of misinterpretation and elision are mine and please point them to me for named textual acknowledgement. The essential theory is very short, discovery long, establishment very hard experimentation, only possible by superhuman effort but deliciously simple and explanatory. There is no reason why it cannot benefit every one, completed by my prediction of 2030, useful to all regardless of preparation, perpetual youth even if obese, sick or exercise-avoid er etc. Aging is really a disease; no medicine ever discriminates.

It is so simple, so universal  plants, fungi, animal - anything having a DNA. Imagine a two gene DNA A, B. All non-evolution morons stop here. DNA with this capacity will evolutionary only will survive! That is far more then all DNA without. a DNA gets this capability, it survives. Say A on means divide, ie propagate. B exists only some task. Now A generates a protein that can also do task of fix. The protein can only work when A is off. Sp A is shut when fixing B. This means cell as a whole cannot divide.
The protein goes to B, turns the gene on, fixes the DNA break, if possible, and turns off the gene. So while the repair is being done, dividing is off. If DNA is missing this correction, the mother and daughter get wrong genes. This happens because cells replicate by unwinding the helix into two strands and throughout replication, only one point joins two strands. A break is duplicated with wrong number of genes because the whole DNA after the break is lost. So mother and daughter are both faulty! We solved this problem in our DNA by suppressing the urge to divide and fix at same time.

The break can happen at any time at random, from UV radiation, pathogens, x-rays etc. That cell dies become much rarer. Means slow aging or cancer.

If we only limited to why? then only  biology. This is a magic time where 4 Yamanaka factors exist for another reason - convert any cell into pluripotent cells. One of the factors generates CANCER. Other three can be controlled to reverse a cell to various degrees of specialization. These modified cells can be used to replace erroneous cells. The critical point is that these are patients own and hence will generate no mismatch!
Another direction is not depend on replacement but fix cells in place by changing their age. Perhaps future will see these two methods applied by circumstances after research.

Monday, June 8, 2020

Epiclock - Epigenetic weltanschauung




semantics: Every where, objective in the sense of judgement of randomly selected jury, is implied even if missing.

Enabler We report here that epigenetic ageing is not affected by replicative senescence, telomere length, somatic cell differentiation, cellular proliferation rate or frequency - Rapamycin Retards Epigenetic Ageing of Keratinocytes Independently of Its Effects on Replicative ,Senescence Proliferation and Differentiation ..

Accuracy The median error of estimated age is 3.6 years across a wide spectrum of tissues and cell types [10], although this increases for older individuals[22] The epigenetic clock performs well in heterogeneous tissues (for example, whole blood, peripheral blood mono nuclear cells, cerebellar samples, occipital cortex, buccal epithelium, colon, adipose, kidney, liver, lung, saliva, uterine cervix, epidermis, muscle) as well as in individual cell types such as CD4 T cells, CD14 monocytes, glial cells, neurons, immortalized B cells, mesenchymal stromal cells.[10] However, accuracy depends to some extent on the source of the DNA.

https://en.wikipedia.org/wiki/Epigenetic_clock ; https://hms.harvard.edu/news/epigenetic-clock


Epigenetic democracy Even better than minimal life, happiness and freedom is prolong life with the goal of conquering death. It has  begun with the development of epigentic clock that measures bio-age better and is hence better than the objective wall clock. Any weltanschaung that improves population epiclock better is objectively superior than other weltanschauungs. A population can objectively measure the performance of its political leaders by even a good statistical survey!

Democratic death Independence is a measure that is perhaps less important as death, but legal stupid belief transcend even death. You can try to convince for an objective period but then give unlimited criticism post death. Certainly included are death is natural, accept no blood, the child will die, wrong to artificially extend life, i am tired of pain etc. Certainly excluded are no prospects, done badly in exam or love etc that are listed in illegal suicides. In between the explicit lists are issues to be solved by judiciary, or politics in time bound manner to extend the lists. This generic solution will be applied to all related explicit lists.

<Massive brain set of the class, friends and family is invited to contribute para, included in above, or respectable contributions, as per me, to me. ~All para to carry name preferred by contributor>

Excerpts and reactions from lifespan by Sinclair 2

 Excerpts and reactions from lifespan by Sinclair 2

[chapter 4][part]

[ poetic description of early evolution - likely but irrelevantly wrong]
[I have named Digilog what Sinclair calls information theory. I consider his work like Darwin and expect many theories, aspect different, but all derivations. This lets Sinclair himself contradict aspects, digilog is Sinclair information theory 2020]

The genes themselves aren’t novel. All life in the lake has these two genes. But
what makes M. superstes unique is that the gene B silencer has mutated to give it a
second function: it helps repair DNA. When the cell’s DNA breaks, the silencing
protein encoded by gene B moves from gene A to help with DNA repair, which
turns on gene A. This temporarily stops all sex and reproduction until the DNA
repair is complete.
[Fundamental to Digilog is the idea
that tight spooling of double helix DNA in parts shuts off the genes expressed there - Gene-silencing. A break is disastrous, but may be repaired by builder genes called sirutins. For this to happen, all activity of DNA is stopped, local gene part unwound [coiled tightly is same as silenced], break fixed and gene silenced again. Normally works but error manifest as aging or cancer]

[How did it happen? Stupid religionists simply see their God did it. Dumber truly animistic are intelligent design advocates who will see a watch-maker, to silence these sub genes even a plausible narrative makes sense, but not in study mode]

In future multicellular organisms, for
instance, cells that fail to pause while fixing a DNA break will almost certainly lose
genetic material. This is because DNA is pulled apart prior to cell division from
only one attachment site on the DNA, dragging the rest of the DNA with it. If
DNA is broken, part of a chromosome will be lost or duplicated. With a new type of gene silencer that repairs DNA, too, M. superstes has an
edge. It hunkers down when its DNA is damaged, then revives. It is super primed
for survival.

And that’s good, because now comes yet another assault on life. Powerful
cosmic rays from a distant solar eruption are bathing the Earth, shredding the
DNA of all the microbes in the dying lakes. The vast majority of them carry on
dividing as if nothing has happened, unaware that their genomes have been
broken and that reproducing will kill them. Unequal amounts of DNA are shared
between mother and daughter cells, causing both to malfunction. Ultimately, the
endeavor is hopeless. The cells all die, and nothing is left.

Nothing, that is, but M. superstes. For as the rays wreak their havoc, M. superstes does something unusual: thanks to the movement of protein B away
from gene A to help repair the DNA breaks, gene A switches on and the cells stop
almost everything else they are doing, turning their limited energy toward fixing
the DNA that has been broken. By virtue of its defiance of the ancient imperative
to reproduce, M. superstes has survived.

When the latest dry period ends and the lakes refill, M. superstes wakes up. Now
it can reproduce. Again and again it does so. Multiplying. Moving into new
biomes. Evolving. Creating generations upon generations of new descendants.
They are our Adam and Eve. Like Adam and Eve, we don’t know if M. superstes ever existed.

But my research over the past twenty-five years suggests that every living thing we see
around us today is a product of this great survivor, or at least a primitive organism
very much like it. The fossil record in our genes goes a long way to proving that
every living thing that shares this planet with us still carries this ancient genetic
survival circuit, in more or less the same basic form. It is there in every plant. It is
there in every fungus. It is there in every animal.

[There is something magical here. May be, we can find old DNA and recreate dinosaurs. Basic to Digilog is the idea of old backup being present in every cell, pushing its existence to pluripotent state by Yamanaka factors. All the genetic developments are there for cloning!

Missing are wombs, but some related species may provide environment needed for Adam/eve birthing.
Finding intact DNA so old may be hard unless one finds an old mosquito preserved in amber! But sabre-tooth tigers preserved in Siberia might be doable!]

[The book here becomes fascinating bottom-up research, for which you have to get it as it explains why yeast, then mice and finally human. Horvath clock uses increasing methylation for very good predictions of remaining life. Not much more re theory! Book crucial to understand why this is NOT a narrative of very advanced person but a true rational-septic who questions self and performs many experiments. The theory took 20 years even if done by 2000 AD! Every phenomenon tested and reco tested against Horvath clock!]

Saturday, June 6, 2020

Excerpts and reactions from lifespan by Sinclair 1


[
self link  https://aaqg-arunarya.blogspot.com/2020/06/digilog-new-paradigm-shift-in-aging.html for latest

https://www.pdfread.net/ebook/lifespan-by-david-sinclair-pdf-read/

As I read the most anticipated life-transformational book by the grand-master Dr. Sinclair, it appears to me that it shares one attribute with the previous life-transformational book, meditations by roman emperor Aurelius five years ago - it is a set of notes to self without the idea of publishing - too slow in parts and too fast in others. The quaity of the message makes the pacing irrelevant, one made me a stoic, other makes me a follower of Digilog. These are for the glory of the new Grand-master whose most attractive dedication reads in part: And to my great-great-grandchildren; I am looking forward to meeting
you.


https://aaqg-arunarya.blogspot.com/2020/06/digilog-new-paradigm-shift-in-aging.htm

My stuff is in []. Very hard to believe, Sinclair is 50, and all his family listen to him and are doing very well.
]

[chapter1]
Growing old may seem a distant event, but every one of us will experience the
end of life. After we draw our last breath, our cells will scream for oxygen, toxins
will accumulate, chemical energy will be exhausted, and cellular structures will
disintegrate. A few minutes later, all of the education, wisdom, and memories that
we cherished, and all of our future potential, will be irreversibly erased.

I learned this firsthand when my mother, Diana, passed away. My father, my
brother, and I were there. It was a quick death, thankfully, caused by a buildup of
liquid in her remaining lung. We had just been laughing together about the eulogy
I’d written on the trip from the United States to Australia, and then suddenly she
was writhing on the bed, sucking for air that couldn’t satisfy her body’s demand
for oxygen, staring at us with desperation in her eyes.

All I could think was “No one tells you what it is like to die. Why doesn’t
anyone tell you?” “Every death is violent,” [documentary filmmaker Claude Lanzmann] he said in 2010. “There is no natural death, unlike the picture we like to paint of the father who dies quietly in his sleep, surrounded by his loved ones. I don’t believe in that. Even if they don’t recognize its violence, children come to understand the
tragedy of death surprisingly early in their lives. By the age of four or five, they
know that death occurs and is irreversible. It is a shocking thought for them, a
nightmare that is real.

[chapter 2]
[Grandma Vera.] By her mid-80s, Vera was a shell of her former self, and the final decade of her life was hard to watch. She was frail and sick. She still had enough wisdom left to
insist that I marry my fiancee, Sandra, but by then music gave her no joy and she
hardly got out of her chair; the vibrancy that had defined her was gone.
Toward the end, she gave up hope. “This is just the way it goes,” she told me.
She died at the age of 92. And, in the way we’ve been taught to think about
these things, she’d had a good, long life. But the more I have thought about it, the
more I have come to believe that the person she truly was had been dead many
years at that point
.

Growing old may seem a distant event, but every one of us will experience the
end of life. After we draw our last breath, our cells will scream for oxygen, toxins
will accumulate, chemical energy will be exhausted, and cellular structures will
disintegrate. A few minutes later, all of the education, wisdom, and memories that
we cherished, and all of our future potential, will be irreversibly erased.

I can also very well remember our oldest child, Alex, learning it.
“Dad, you won’t always be around?”
“Sadly, no,” I said.

Alex cried on and off for a few days, then stopped, and never asked me about it
again. And I’ve never again mentioned it, either.


For Robin Marantz Henig, a columnist at the New York Times, the “bitter
truth” about mortality came late in life, after she became a grandparent. “Beneath
all the wonderful moments you may be lucky enough to share in and enjoy,” she
wrote, “your grandchild’s life will be a long string of birthdays you will not live to
see.”

It takes courage to consciously think about your loved ones’ mortality before it
actually happens. It takes even more courage to deeply ponder your own.
What’s the upward limit [of life]? I don’t think there is one. Many of my colleagues
agree. There is no biological law that says we must age. Those who say there is
don’t know what they’re talking about. We’re probably still a long way off from a
world in which death is a rarity, but we’re not far from pushing it ever farther into
the future.

All of this, in fact, is inevitable. Prolonged healthy lifespans are in sight. Yes,
the entire history of humanity suggests otherwise. But the science of lifespan
extension in this particular century says that the previous dead ends are poor
guides
.

[ As a stoic, I know what death is - a contemptible event, life meaning-less, no. of days irrelevant. But I am alive at the first time when death can be conquered in my lifespan by 2030 by methods that make sense to my rational-skeptic mind who has schemed to become guinea-pigs early enough to enjoy first extended life but late enough that major bugs are fixed! This I call the when problem. Why me is called the whyme problem., only solutions are money and world unique encryption which is quantum safe even if Shor capability happens in quantum computers. How problem is also there, imagine that Brigham and MGH are both tied to Harvard as is HCHP in which my ex-wife worked [First h is Harvard]. Time to reignite friendship. Wish-death needed as will run many spans due to needed recovery from TBI! The only scientific-hence-believable solution is integrated AI]

Digilog - new paradigm shift in Aging


A paradigm shift is a revolution that destroys ALL old methods and concepts and by definition, destroys experience. As a member of computer science, I have witnessed several paradigm shifts and destruction of all my friends but me, who smartened up fast, changed to academia and sincerely busied myself in research, redoing all with each shift.

This is my first piece and tells what was a(later) and why this is a paradigm shift. Digilog  is my neologism for this new paradigm, portmanteau from digital+analog, the generation is by Dr. David Sinclair who calls it theory of information, who along with Dr. Aubrey de Gray are the only doctors who make sense, and are both originally non-MD! In other words, digilog will hopefully force ALL MD to retire from AGEING, and destroys gerontology and geriatrics, both being staffed by inconsequential now till they learn and start using digilog concepts.

The first surprise is that perpetual youth and end of Aging are the same thing! That is because end of Aging is like jellyfish. second: It will work because it depends on Yamanaka factors (Nobel prize) that convert any cell to its pluripotent form. Right things are not as any per any religion, but evolution. Aging is from Cellcide from analog epienome transcription errors on broken digital DNA.

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

50 min long. MOST valuable video you will ever watch - Socrates-video not capable of summarizing.  Either you become convinced, or remain stupid - maximum strong words from me. It is falsifiable, hence a scientific theory. It treats Aging as a disease, not a source for any ethics. It works on all animals, easy for  evolutionist as me. Healthy things it propagates have zero value beyond your own health! Hopefully, you will NEVER abuse word natural again - death is NOT natural but consequence of bad life choices, not following empirical techniques  and lack of knowledge. I think it will be wish-death by 2030 (corona ends 2020 with CQP)!

Tremendous concept of Horvath clock and sane blood tests feedback. (Later)

Wednesday, June 3, 2020

HCQ etc




Much flip-flop on HCQ. I believe it was being administered to Dharavi residents as a prophylactic. Perhaps other slums too. Haven't heard about the outcome. Sir Mohoni
10:42 AM

HCQ and phosphate are different despite sharing quinine - HCQ is Trump baby, chinese scientists are equal to best west, never-mind USA now; but Govt captive.

I am NOT a professional chemist, the phosphate ion makes it acidic while HCQ is a base pH from OH-.

a study in The Lancet Rheumatology has found that hydroxychloroquine decreases the acidity in compartments in the cell membrane. Since many viruses use the acidity of these compartments to breach the membrane and set off the process of replicating copies of itself, the reduction of acidity can potentially inhibit viral replication. In 2005, the drug was used to treat SARS, but it failed to decrease the viral load in mice. HCQ probably works for very few.

Rajasthan doing HCQ for police. I suspect non-bjp folks but HCQ is failed Trump baby! These govt. not acting on results!

I suspect virus does penetrate compartments but then gets killed by quinine or phosphate or both.

I read somewhere that the US is administering four times the dosage that we are, and that has caused the reported complications and deaths - Sir Mohoni

 
US problem of plenty! If x is good, 4x should work miracles!

Tuesday, June 2, 2020

choroquine phosphate repurpose break-through for corona



from chinese, official US translation

https://pubmed.ncbi.nlm.nih.gov/32075365/
[Expert Consensus on Chloroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia]
... Department of Science and Technology of Guangdong Province and Health Commission of Guangdong Province for chloroquine in the treatment of novel coronavirus pneumonia developed this expert consensus after extensive discussion. It recommended chloroquine phosphate tablet, 500mg twice per day for 10 days for patients diagnosed as mild, moderate and severe cases of novel coronavirus pneumonia and without contraindications to chloroquine.

 https://pubmed.ncbi.nlm.nih.gov/32074550/?from_term=%22COVID-19+drug+treatment%22%5Bnm%5D&from_pos=1
Breakthrough: Chloroquine Phosphate Has Shown Apparent Efficacy in Treatment of COVID-19 Associated Pneumonia in Clinical Studies
Jianjun Gao,, Zhenxue Tian , Xu Yang
 Abstract

The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China for treatment of COVID-19 infection in larger populations in the future.

Arya
1. unlikely a hype -- too official
2. china did fool the world, emerging late but at least
3. west pharma-scientist  hit but so what? Recommend continue fina ncial support for a month
4. Easy to build after quick ramp up in India
5. Repurpose means known side effects

Monday, June 1, 2020

More vitamin D



First regurgitating what written 1 month back as end this missive. Did not stress it much as most of folk were engineers at MIT etc. Now the claim is also made by MGH doc. Harmless waste of money if not as good. Suggest consider 60000 IU. Per week or 15 days of vitamin D3. Talk to doctor first. D sold as sachet once/month 60000 IU. Use it per week.

Overdoses not possible. AN ortho doc told me re medical education 40 years back, they wrote prescriptions for 500,000 IU per week! Alternately, remove shirt and sit in Sun in India (no shirt) for 30 min per day!

Talk to doc ASAP. Most of us are 65+ and need D3 fast!

Vitamin D deficiency may be linked to more severe cases of COVID …

 



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

D vitamin
The researchers also found a strong correlation between vitamin D levels and cytokine storm, which is a hyperinflammatory condition caused by an overactive immune system.


"Cytokine storm can severely damage lungs and lead to acute respiratory distress syndrome and death in patients," Ali Daneshkhah, a postdoctoral research associate at Northwestern's McCormick School of Engineering, said in a statement. "This is what seems to kill a majority of COVID-19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system."


Arya
1. Eating d3 as part of [k2, d3, ca]
2. explains low rates in india etc high italy, france, usa etcbecause melatonin - we brown/black
3 anyway good although oteoporosis/penia common from lack of ca and no k2 in diet like chinese or japanese, addind d good as overdose NOT a problem - jusst wasted money and d cheap