Saturday, July 4, 2020

Living long


My father lived to be 88, would have lived to 98 (I think0 BUT FOR HIS WEAKNESS RE MANGOES. For men, metformin AND acarbose synergestically work better than each other, while both improve healthy life. Acarbose fails longevity in women. Both benefit from rapamycin, though toxic in long use. As a diabetic on both, I expect to live 15 years beyond my undiabetic life! 98 to 110 with current interventions. NMN targets Sirtuin, Metformin targets AMPk while rapamycin target mTOR pathway.

Researchers have demonstrated that acarbose, a drug used to treat type 2 diabetes, extends life in mice. This should probably be taken as speculative until more studies are run, as another treatment for type 2 diabetes, metformin, has erratic results on life span in rodent studies. Like metformin, the mechanism of action for acarbose involves influencing glucose metabolism, though in a completely different way.




The present meta-analysis aimed to evaluate metformin combined with acarbose compared with monotherapy with either of the two drugs for type 2 diabetes (T2DM). Relevant trials were retrieved through searching PubMed, Embase, Cochrane library, China National Knowledge Infrastructure, Wanfang and Chongqing VIP information network databases. Heterogeneous and homogeneous data were statistically combined using a random- and fixed-effects model, respectively. For dichotomous and continuous data, the merged effect size was presented as the risk ratio (RR) and weighted mean differences (WMD), respectively, with 95% confidence interval (CI). All included studies were divided into subgroups. A Funnel plot was used to detect publication bias. Review Manager 5.2 software was applied to perform the statistical analyses. Meta-analysis revealed that compared with metformin monotherapy, combined therapy was significantly more efficacious regarding indexes including the total effective rate, fasting blood glucose (FBG), blood glucose levels at two post-prandial hours (2HPG) and hemoglobin A1C (HbA1c). Similarly, combined therapy showed advantages on indexes including FBG, 2HPG and HbA1c over acarbose therapy after 4 months of treatment. In conclusion, the findings of the present meta-analysis suggested that combined therapy of metformin and acarbose appears to be more efficacious than metformin or acarbose monotherapy.


Recognizing that aging can be targeted, the NIH developed the NIA Interventions Testing Program (ITP). The ITP tests diets, drugs, or other interventions to see if they prevent disease and extend lifespan in genetically heterogeneous (outbred) mice (http://www.nia.nih.gov/research/dab/interventions-testing-program-itp). This program is conducted at multiple centers in order to control for laboratory-specific environmental differences, and testing is done in both male and female animals (Miller et al., 2007; Nadon et al., 2008). Major findings of the ITP include that nordihydroguaiaretic acid and aspirin each increase lifespan of male mice (Strong et al., 2008) and acarbose and 17-α-Estradiol extend mouse lifespan preferentially in males (Harrison et al., 2014). Studies of rapamycin (an mTOR inhibitor) have established the most compelling evidence for targeting aging. When rapamycin is administered late in life, it extends lifespan (Harrison et al., 2009; Miller et al., 2011), slows aging in a dose-dependent manner, shows differential effects by sex (Wilkinson et al., 2012), and is synergistic with metformin.


Acarbose "alpha-glucosidase inhibitors" (why it works), 17-α-estradiol, and nordihydroguaiaretic acid (metformin relative) extend mouse lifespan preferentially in males
. 17-α-estradiol is  feminine, why (I think) human women live longer and it does not impact women mice.


Thursday, July 2, 2020

Weltanschauung - who am I - prologue:



Top

Popper https://en.wikipedia.org/wiki/Karl_Popper


who am I - prologue: At 25, I finished my Computer Science PhD.D thesis defense, and stood outside math science tall building with knowledge that the next strong memorial convocation happens with the degree roll for me. I had completed the mercy-less program and I was an employee at Boston doing software for the US army, best I could do, and worst according to my guide, who had become my father and hence took the position as me a misguided young man! His scornful look zeroed my pleasure and I was agitated. The program took me 3.5 years of toil and ended successfully. "What next?" I asked myself, worried by yet another Father I had upset. That fateful afternoon, I decided I will spend the next 4 years of my life (as long as I spent on PhD.) or less, and answer it well to answer my doubts - who am I.

deepest? A life went by. I am 65 about 40 years later and have finally been able to answer it to my satisfaction. How was I to know that this question is deepest in philosophy and touches all aspects of my life. You, my dear reader should read it once to answer it for your own self. Many times to begin to know me. It is unique in how much the question is covered.

writing style: It is written in a particular style, similar to how every intelligent scientist I encountered in the last 40 years whose style I could parse, think, and so do all top professors. I call it Socrates/style. Throughout, phrases with a slash, are mine with detailed semantics as per me and grossly, but not in fine details, without ever being surprising coarsely. In it, a question is asked, constraints on solution are imposed, and then one researches the answer, which might be simple or deepest like what I asked, depth not known. It has no relations to events in my life, most events are much better understood now. Its epistemology, like all science, is falsifiability https://en.wikipedia.org/wiki/Falsifiability. That here can even be the answer to "Who am I" is a 2020 miracle, never before in human existence [I prove it]!

Plethora of sub-questions: The question resolves into many more. For each there is a falsifiable (scientific) answer here. All religions are equally stupid, they are all equal so [I prove it. What is the universe around me - society, people, stars. What is life I have and how valuable - my own, family, friends and soldiers who fight for me. What is death, is there an afterlife, can I influence it? What is ageing, how can I minimize its harmful impact on self and loved once? What is medicine and sickness. How does one minimize its harmful impact? How does one distinguish money-drive salesmen and genuine value adders. How does one escape advertising and use it profitably! How does one escape politics and use it profitably. What is history, baloney and use if well? How to escape those who understand this. What is law and semantics? What is consciousness? Can one make Artificial Intelligence AI to understand and do what lawyers, doctors, teachers, maintain robots, white-collar jobs. How will post-industrial world function? Can robots be conscious? Who, what, how to believe? What makes society around me function. Who am I?

40 years later:  I will answer in subsequent pages. Just the width of sub queries is frightening to all but religious. I consider those beliefs to be uncivilized and support measures to drive them underground. The basis of all questions asked above is science, and lack of any belief in Any book or tome except as detailed by active rational skeptics whose words are treasured as representative of me. Even then, unless old enough to withstand active scientific investigation, else the statements are not a theory but a hypothesis. My great belief in Talib and Sinclair are such that their statements are hypotheses. There are All religions whose every contradictory statement means the converse is likely a hypothesis (Mal/hypothesis)!

what is science: pointless to talk about scientific without knowing what it is. Every religious moron will use the word unscientifically, in fact a collusion between his beliefs and science, not even knowing it is impossible. By Popper definition, generally accepted, science is a collection of falsifiable theories! Not one religious idiot considers religious facts as falsifiable! That is a negative constraint on what science can not be. On the positive side, science is rational skepticism, you only accept testable empiric, never believe unless it meets your logic! If accepted science fails, then your logic is faulty. It never happens with ordinary things. Extremes of size and speed in science force you into quantum mechanics and linear logic. Except quantum phenomena, ordinary propositional logic and predicate calculus suffices. There is nothing more laughable and scornful more than a stupid religious joker applying quantum mechanics to anything.

Who fails the Popper test? Not only do all religions fail, so do many phenomena considered scientific - like multiverse, what happens in a black hole, why is vacuum energy what it is etc. There is an element of rigorous deduction, inviolable known science axioms - limiting to new axioms not tested to today. Even then, it is not science. Science has no claims to be known all ever, it is that ALL religions fail unfalsifiability! ALL sub animal politicians have to become proficient in the art of attractive meaninglessness which can not fail! Said my favorite emfubar Sir - Modi failed Corona, not because he copied west like the US and UK, and failed to follow east like Japan and Sweden (sic) ; but because he failed to follow the Indian way! Not a word about the superior Indian  way! The explanation of Modi errors - so many of them - is simple, he is afraid of Sir. Sir Trump is a failure because he is not properly patriotic enough! Why do you think the intelligent Americans never argue with an Indian brahmin saint ever again?

outline of answers? This text was not possible before 2020 before I read Dr. Sinclair (Harvard) aging theory of information I applied to self as derived digilog theory two weeks after I read and saw some benefit. I tested positively once on  self, will again test on the month mark then life long on the annual mark. I suggest this digilog schedule and its understanding. Best I can suggest is to read and intern his book published in 2019. It is a scientific theory (falsifiable) and not dependent on any authority but sequence of experiments that all can try. I myself have formulated some empirical tests to try the digilog theory. Will be budgeted and done. Unless I could apply myself successfully, writing the rest of the questions is a waste of my time.

Contents Weltanschauung - who am I



Next
contents
Prolog
What is the universe around me - astronomy
Society - What is it around me
People - What is it around me
What is life
My religion
Value of my life
Value of life to family
Importance of friends
Dedication to soldiers
 What is death
Afterlife
Can I influence it?
What is ageing
How can I minimize its impact on self
Impact on loved once
Money-driven salesmen
Advertising  profitably
Escape politics
Politics profitably
What is history
Historical baloney
Abuse of politics
How to escape those who understand this
Non formal law
Semantic genuine value adders
Consciousness
Artificial Intelligence AI
AI - do what lawyers
AI -do what doctors
AI -do what teachers
AI -maintain robots
AI -white-collar
How will post-industrial world function?
Can robots be conscious
Who to believe
What to believe
 How to believe
What makes society around me function
Who am I?

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

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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

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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

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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
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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

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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

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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