Friday, September 25, 2020

undoing ageing

 


 These are truly unique wonderous times. For the first tme in human history, a true scientific path to undoing aging is within reach. Whine philosophy is minimized, scientific means within the capability of legal MD, irrelevant are belief systems of the beneficiary, like allopathic medicine effectiveness is the same for sinners, criminals and upright citizens.

There are many ideas on undoing ageing, referenced in past. I BRIEFLY MENTION THE ONES I WILL FOLLOW. There are other methods that may become more important in futute, so there is no total commitment on way to proceed, except lifelong commitment to evaluate. This attitude can be taken by me as a follower of research, not a researcher, but even here I have to restrict for saving time and reference lookup costs. I am smart enough to know my limitations and that certain references need to be followed, while others can be ignored for being support for simple things or similar or identical to ones already followed.

non-science methods?

All guru, tomes, witnesses are uniformly all bullshit. Have no time to waste even listening, leave interning!

parbiosis?

Veins of mice  of distinct age are sugrically joined to a common circulatory system. The rates of elder mice and younger mice are compared to similar free mice. Recovery from injuries, disease, stress and digestion of the elder mice are found improved.

One does not have to resort to parbiosis ghoulish effects to benefit. The same effects can be obtained by inserting young plasma. Plasma recovery is twice as fast as blood donation, without the fatigue felt after blood donation. This happens because the donated blood is filtered to remove the red cells which are reinserted in the donee. Plasma donation is simpler as blood type distinctions are missing and plasma banking is easier. Plasma can be sold twice a week!

The reason why plasma suffices is that it carries hormones and dissolved organics. What they are,is not known and there is no reason but science, to know. Clearly, the plasma can be enriched, equal to iv add of the chemicals. The whole idea of parbiosis is to undoing ageing, not knowing what ageing is!

One of the most useful effects of Covid is to use plasma in a similar way by transferring anti-bodies to the patient! Delhi has recovery bank blessed by the government. Certainly, the government will not object to repurposing the technology developed!

telomere?

While more developed (Columbia runs an age reduction trial, each member of test coughs up milion dollars), I will not follow because lab scientists have reported failures to now. Additionally, mice have perfect telomeres but live 3 years! The trial above, till results prove me wrong, is snake oil for the gullible!

https://www.prnewswire.com/news-releases/breakthrough-gene-therapy-clinical-trial-is-the-worlds-first-that-aims-to-reverse-20-years-of-aging-in-humans-300963496.html

Yamanaka factors?

Yamanaka-factors revolutionize and ethicize genetics. Determined by very hard experimental work, twenty five chemicals were very smartly  screened to 4 OSKC, which when applied to any DNA convert to its pluripotent form (that is prior to differentiation!)

Most exciting to me is Horvath clock demethylation of the epigenome. Horvath identified 373 sites in human genome DNA (experimentally) and showed that calendar age could be predicted from this biological age (bioage) to  within 3.6 years. You need to measure methyl concentrations at these points. Improvements by US companies has allowed them to claim within 1.6 years. Bioage is very important since it allows science of ageing. Epi-mark are better than DNA-marks! Most importantly, underlying DNA is fixed in the womb. This allows eventual scientific fountain-of-youth.

With proper schedule, the OSK (C only induces cancers) can be used at low amount which reduce ages of differentiated cells without losing the differentiation! Thus drugs can be made for avoiding ageing specific to differentiation.

One can even operate genitically in Cas-9 cuts and restore within the selected context of cas-9. The dajnger is lack of specificity of context which may appear many times. No one has implemented (to my knowledge) additional contexts by surgery. Idea is to remove small chunks through surgery, perform cas-9 updates and surgically replace the amount! The genetic manipulation is now surgically enhanced! This is not useful in the past but very possible in laproscopic surgery!


How Yamanaka factors are the best way.

There’s a preprint from David Sinclair’s Harvard laboratory, posted on BioRxiv but not yet published, with very encouraging news for those of us who think that resetting the epigenetic (methylation) clock is a path to anti-aging.

study from the University of Exeter in England focused on the reverse aging of human genes by focusing on senescent cells and what are called splicing factors. The latter is a type of protein involved helping genes express themselves normally, but as we age, the process of senescence, or a state in which cells stop dividing and slip into a state of growth arrest without dying, causes the cells to be inactive and essentially turn off.

Is Arun finally a mental gone case or harbinger of tidings that are essential to all friends. Answer is believability, in this case the top cetainly conservative science magzine the scientific American over 150 years! 

Aging Is Reversible—at Least in Human Cells and Live Mice https://www.scientificamerican.com/article/aging-is-reversible-at-least-in-human-cells-and-live-mice/

The researchers found that by applying a compound commonly found in wine and foods such as dark chocolate and blueberries called resveratrol, they can actually reverse senescence and cause the splicing factors to reactivate.

Research has indicated that aging is actually an epigenetic process, or in other words it is often fueled by nongenetic forces, such as the environment we live in. A 2016 study published in Cell found that by tweaking genes that turn adult cells back into embryoniclike cells (pluripotent), scientists were able to manipulate the behavior of human skin cells.

The researchers found that by applying a compound called resveratrol, they can actually reverse senescence and cause the splicing factors to reactivate.

One of things I do - 1gm reservatol per day, Rs. 6000 (thousand) for 6 month supply, copying Dr. Sinclaire (Harvard), discoverer of why we age! Redo nmn, nr, or nad when can get prescription for iv or injection form.

Can Science Reverse Aging? https://html.duckduckgo.com/html?q=yamanaka%20ageing


Sunday, September 6, 2020

THE SCIENTIFIC THEORY OF AGING



What does a scientific theory mean? Absent a clear definition, every emfubar, while demonstrably an fubar, will claim science as part of a fubar belief system. Any statement becomes a scientific hypothesis only when it satisfies by negation the falsifiability test of Popper, and positively being a rational skeptic who never ceases a why. Ultimately the infinite regress leads to astronomical evolution which can be continued to about 10-21 second after big bang. What was before that, assumes there was a before, not necessary by any scientific theory. There are many cosmogenies that imply there was a before, but as a basic axiom. One of Cosmogonies in fact says that big bang is when time began. Note that time becomes infinitely slow at the speed of light and that spent by a photon despite coming from eons away is still zero. Neutrinos are matter traveling almost but not nearly light experience time, enough to change flavor in flight unlike photons which have same frequency fixed at creation time.

So what is the theory of Aging? It must be consistent with all known physics, chemistry and biology. It must be provable in the sense that some feature of the theory, on violation speeds up or reduces age. This must be simple enough to be allow performance in peer laboratories without requiring consultation with the author. In other words, experimental evidence can be collected and compared absent the author. This external repeatability is essential to science. I add another test peculiar to me - no external force (like God) may be invoked to explain all life on earth, this is not necessarily a denial of God, just the requirement God concept is not needed. All life can be explained (despite intelligent design pseudo-science) through evolution. This evolution-compatibility is my requirement and holds for Sinclair's theory. It even explains why all life on earth has a DNA basis, why fountain of youth is possible without time travel and why other forms of DNA do not exist. We might never encounter any other DNA.

It is a DNA based theory. The simplest form of consistent Circuits, despite other species based genes, is a fundamental requirement that the protein generated by a repair gene prevents the duplication of the DNA i.e. the cell. This exclusionary behavior is anti-simplistic understand of biology of evolution where replication is assumed to always be reason of existence of any lifeforms. True, but ageing is below a cell which has many species' dependent extra parts to the nucleus DNA molecule which is a giant double helix in all forms. Genes are simply small parts of the giant code. Operations are all done by allowing proteins to form by copying portions of DNA. The two cell level processes are duplicate and apoptosis. Duplication can be prevented internally by shutting of duplication gene while repair is in progress. The cell duplicates by unwind the double helix to 2 one strand parts, each of which forms a double helix by element duplication. The whole process takes time and exclusion circuit prevents duplication while unzip happens. This prevents error in the mother and daughter molecules.

Carefully note that any other DNA molecule, without the exclusion circuit, will fail after each coincidence of an error and replication. Errors happen all the time - x-ray, solar activity, stress, bad food etc. Unless DNA can recover some, the lifetime is milliseconds. Even with amelioration of errors, for animals, lifetime is few days to 300 years - cancers limiting life. EVEN TREES LIVE A FEW THOUSAND YEARS. Errors eventually add up and kill. The problem of ageing is too complicated to be solved by biology alone. But extending biological life can enable time for development of cyborg appendages to complete transfer to silicon life.

The fascinating corollaries to above are


1. The correctness of proof of above theory does not lead to any anti-ageing prescription


2. The systemic environmental interventions are all in the epigenome. underlying the epigenome is pristine DNA, as pristine as birth. Extending age and fountain of youth are the same thing.

 

Here are other possibilities.

HORVATH CLOCK

Distinct, but scientific, is the proof in 2012 by Horvath in California that all DNA genome and epigenome has marker sites whose methylation is strictly increasing and correlates with calendar age. The prediction rules depend on the species but are remarkably stable on mesenchrymal cells. For an individual of a spies, a table can be used to predict bio age TO within about 3 years of the calendar age.  A table can be prepared in advance per species to predict bio age accurately.

The strictly increasing methylation pattern has very few marks at birth. Amazingly, cells sunjected to yamanaka factors become totiplurasl by shedding the epigenome and the methylation marks of the underlying pristine DNA. Even the mesenchymal changes are not preserved. The cell can begin li8ge anew. But it is rarely a single cell! All the cells revert in unison, and what you get is a ball of cancer.

Amazement follows subsequent research. Of the four Yamanaka factors OSKC , the C is always cancer-genic. Of the 3 others, the degree of specialization removed depends on frequency and degree of immersion, more meaning more reversion. This has immediate applications.

1. The degree of age removal can be judged by starting and ending bio age. There are for example telomere based methods which predict a longer life from telomere restoration, but in this case too, the methylation removal happens. One can not cheat the Horvath clock,

 2. A genetic age reversal process follows by OSK based foods and medicine, subjects of future research.