Tuesday, June 9, 2020

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.

No comments:

Post a Comment