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