The linked paper is not being heralded so, I am either presient or stupidly excitable! I EXPLAIN WHY THIS BELIEF TOO.
Dr. Sinclair has proven that all life on earth shares similar DNA which is everywhere in a nucleolus of a cell. He says that the characteristic of this DNA is that it discovered how to safely patch a break by exclusion of reproduction until repair by turning off the reproduction while the repairs were on by making the reproduction and repair genes the same and expression of repair protein causing the shut (by tight coiling) of the repair portion (the same) by coiling hard IE shut! Such a mechanism has overwhelming evolution advantages over distinct DNA and the only one which survived and is found in all life on earth! The extreme aging of the mouse with inhibiting repair is proof. Regrowth of optic nerves crushed in mice is the rejuvenation proof.
Horovith did wonderful research in totally independent manner and could train AI to predict calendar age from all kind of tissues. They being the same implies genetic aging manner and by 2021 had shown the programs applied to all species of life factored by DNA specialization! This work has been applied to eutherians and will doubtless apply to all life. The variable extract is methylation of specific Cp islands in DNA. An AI can empirically work in all tissues like blood, organ, hair, skin, and spit and predict age within 98% accuracy and predict remaining natural life too. How the methylation occurs is still a mystery and programmed life beliefs are common. I consider non programmed life in the minority, still clinging to the paradigm of damage accumulation and cite two things in my favor: One is matching is statistical, not 100% from a programmed theory; and two the fact that statistical damages can yield so good as adds of random variables; and three that human death age varies from 60 to 110 and death rates flatten after 90 to no age relative extra risk! But the short answer is that it is a programmed process. And there is no clinching experiment yet,
Now comes my orthogonal but essential expertise in formal languages. One can capture DNA derivations by L-systems of context-sensitive grammars with correct context is required for application of a rule. People have babies when the age of the boy is from 14-74 and the age of girl is 13-42. No child has ever been born aged. The DNA of the male when it fertilizes the female is striped clean of methyl marks, as is the woman's and the baby inherits two clean DNA. One can trace the process to 4-fold division after fertilization. The fertilized egg thereafter attaches itself to the womb wall. In the absence of complications, the due date can be predicted accurately within a few days, showing again a 98% accuracy. So there are grounds to believe programmed aging theory paradigm. I however, draw a different lesson from this, one the old DNA is preserved intact; and two the most important one, namely that removing the methylations have a rejuvenation effect.
That brings me the meat of my study, that is the research linked in will be considered a break-thru some day soon.
Summary
A general approach forheritably altering gene expression has the potential to enable manydiscovery and therapeutic efforts. Here, we present CRISPRoff—aprogrammable epigenetic memory writer consisting of a single deadCas9 fusion protein that establishes DNA methylation and repressivehistone modifications. Transient CRISPRoff expression initiates highly specific DNA methylation and gene repression that is maintained through cell division and differentiation of stem cells to neurons. Pairing CRISPRoff with genome-wide screens and analysis of chromatin marks establishes rules for heritable gene silencing. We identify single guide RNAs (sgRNAs) capable of silencing the large majority of genes including those lacking canonical CpG islands (CGIs) and reveal a wide targeting window extending beyond annotated CGIs. The broad ability of CRISPRoff to initiate heritable gene silencing even outside of CGIs expands the canonical model of methylation-based silencing and enables diverse applications including genome-wide screens, multiplexed cell engineering, enhancer silencing, and mechanistic exploration of epigenetic inheritance.
Here is more of my intuition. A Chinese doctor did the very unethical thing some years back - used crispr-cas9 tools of the day to genetically edit human DNA and made a Chinese women carry the result to term. Why the anger worldwide? The edit allows a contextual change in the DNA. But the change will be at all sites in the DNA, whether or not intended. The child may be born with huge unknown genetic disasters, with strange unknown diseases in life! Even most Chinese scientists were aghast, and no such experiment has been repeated.
New method referenced above will prevent unintended edits! The method is new and has applications in my specialty. It works by defining two context around the point of interest. One is the usual crisper cas9 context. Overlaid is another of some width. All genes outside are forced shut. Hence, edit cannot happen! If suitably small region is edited, bad edits cannot happen! The methylation marks can be used to bracket the context! Clearly it will work in context-sensitive grammars where the equivalent to methyl marks can be propagated and derive null at end only! Only one can derive nulls only at the end, thus context-sensitivity is kept. Whether more than 1 nonterminals can be still be nulled in the end is still context-sensitive is open!
Introduction to my specialty
Not to attract one, but just to get a feel, consider it in 2 courses. Scan rapidly if curious.
One is automata theory, essential to becoming a theoretical computer scientist. Another is to become a compiler scientist. Before my devastation in 1990, I was working on attributed grammars, still fortunately primitive, ready for me to shine as professor emeritus, assuming that undo of my age works some, a second career as Dr. Sinclair dad! Incidentally, what makes me very excited is the backward limited understanding possibilities today of attributed grammars in programming languages (still no automatic semantics in compiler-compilers) graphics (all GUI interfaces are context-sensitive, change as you proceed in a program), pre-formatting (HTML is poor, latex too complex), compilers (context-sensitive AI applied to natural deduction like in robots), machine learning (in robot ensuring understands intended orders only) and now aging!
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