Dr. Arun Arya's Unified Hyperfunction Aging
Disclaimers: I am not a medical doctor, but a 20-year deep dive in biology and biochemistry, nor is Dr. Sinclair (NMN, Sirtuins) or Dr. Kennedy (Ca-AKG). I consider myself very smart based on the amazing scientific way they were discovered despite the deafening commercial din. The best way to benefit is to formulate a plan and discuss it with your doctor MD. Even I do it.
I call my theory unified since it joins together top-down Dr. de Grey (as done in SENS and continued in LEVF) and my Hyperfunction extension of Dr. Sinclair's bottom-up Theory of Information
Rejuvenation by damage repair is a fundamental basis of my theory within Dr. de Grey and Dr. Sinclair's paradigm.
First, some intuitive facts (2) must be satisfied by any aging theory. Mine does and it is hard to even imagine any other compliant aging theory.
1. (Fact) No child is born old. Counter-free: Even in extreme populations crucial to valid theories, even in diseased extremes, there are no credible samples. Somehow the joint statistical DNA average age is reset to zero independent of the age of both parents.
2. (Fact) A child seems to be indistinguishably born from women under menopause and males to 75. Somehow, the parent's DNA is preserved during the entire parent's life.
From just these, one believable theory is the “Information theory of Aging” by Dr. Sinclair which says that DNA is preserved in life, and there is an epigenetic layer on top of it, perfect at birth, but degraded in life, simulating aging. Children are born with a statistical average of the parents' DNA genomes, not their current epi-genomes. Dr. Sinclair is the only bio-chemist known whose aging theory is consistent with these observations.
3. (Fact) All scientists must be assumed guilty unless proven innocent, particularly when dealing with the economics of their expertise. The only ways to become truly believable is to use the recommendations on themselves and show credible gains, or submit to full FDA evaluations. Every scientist suffers from aging! Dr. Sinclair does. So do I. It is stupid to believe that he or I are special, not random.
There are two empirical facts independent of whatever religion you believe. These are i) you and all biological life, including plants, on earth are made of 1 to many trillions of cells that even look wrong on seemingly independent things like skin, bones, nails, hair, etc. ii) all life is a consequence of evolution, essential to understanding de-aging. [My belief in evolution is from my derivation of de-aging from it.]
4. (Fact) A cell is a list of cellular material and 1+ sacs of many kinds, particularly DNA in the nucleolus, strength energy from mitochondria, protein factory of ribosomes, waste-basket and waste processor in lysosomes, etc. DNA is a large double helix molecule that is geometrically wound tight with only some parts visible unwound, enabling the same sub-molecule to become one of many as reactions only happen at exposed parts. The ends are called telomere which shorten on every division. Ultimately, they shorten so much that the DNA so much (after 50 - 60 divisions) that the cell does not divide anymore, every division happens (1-2) years. Each mitochondrion has its own DNA and each runs the Krebs cycle, in particular the ADP-ATP subcycle which is for energy and NAD+ for most subcycles. Both mt-DNA and telomere are related to non-DNA aging. The biochemical miracle is evolution discovered perfect copying and shutting reproduction during division by total tightening of the entire DNA molecule. This happens for all virtual sub-molecules. This total exclusion is a mark of terrestrial life and may not have been discovered by any other evolution on another planet of our universe or only sea-based life.
5. (Fact) While all cells depend on the organ they belong to, every cell has identical DNA, folded differently to expose different behavior, but all allow total tightening to prevent copying while error correction proteins are made active. That is unusual behavior to all biological molecules in which copying for propagation purposes is fundamental, all DNA cells can and do no error fix while spawning. This allows evolution to happen, prevents errors in very analog biochemistry, and is true for all DNA in all animals, microbial life, plants, trees, etc. Ultimately every DNA in every cell of a body is the same and OSKM chemicals can convert any cell sequence to global pluripotent form. Recently extinct animals can be revived but not dinosaurs.
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Let us first consider any biological system that forms an animal. We know for a fact that it is a bottom-up cell system with distributed control required in many tasks, parallel done, but sometimes centralized by some organs. The system requires chemicals to reach where required, for which evolution chose blood flow, common in all large animals bigger than or equal to a mouse. This allows evolution to create organs, losing only some reliability from some centralization rather than solving for difficult distributed solutions. Fundamental is life thru reproduction, bi-sex for rapid evolution, and all subsystems can degrade any way after reproduction. Humans could raise life from the thirties at Alexanders' time to the eighties in advanced happy societies. Every bio-system must be weakly protected against other competing systems, even smaller ones based on viruses, bacteria, etc. A general creative solution is possible with blood flow and the immune organ. Various white cells can flow, reaching everywhere as immune cells collectively creates white blood cells.
Every bio-system lives and dies, the dead body must be deposed somehow. Animal bodies have predators, ants, and soil bacteria. Cell bodies generate a lot of waste, all handled by internal lysosomes.
All biological systems can fail - spontaneously or by aging. All these failures can happen in near cells and produce disease. Lysosomes can attempt to degrade evil junk unsuccessfully, bloat to kill the cell itself, and cause disease. Then just another source of more junk.
All systems have an inside and outside. For animals, it is the body and environment. For cells, it is intracellular and extracellular. It turns out that for extracellular, two kinds are distinct - extracellular material crosslink and foreign bodies including dead cells.
Cancers have only one thing in common, they discover how to make a cell indestructible by the generation of fresh telomerase by activating the telomerase section of the DNA. Due to exponential bio-population, the foci rapidly expand with new blood veins initiated and supplying the monster again finding in the DNA.
1 A body in all Eutherians is trillions of cells in the skin. The skin itself is a cell construct exposing water-resistant parts of DNA. Cell collection has no stiffness and is incapable of forming stable 3D structures, hence a skeleton is needed, obtainable cross-species as no cells are imported. Thus skin contains cells embedded in outside proteins in which cells are. The externals molecules degrade in 2 distinct similar chemical ways - foreign or degraded proteins, and wrong extra links in the external proteins by cross-links. Damage-repair engineering must remove foreign/degraded material as well as the crosslinks.
2. Very hard in biology is to get rid of dead or unwanted remains. The basic method is for neighbors to collectively raise the apoptosis signal. This signal is honored by healthy cells or forced on by the immune system B and T cells. They can cut the diseased cell into small pieces, and garbage collected by blood is eliminated by the kidneys eventually. The problem is when you are old enough to have a weak immune system. Another problem is in the brain where the BBB allows only small molecules through. Even when amyloids are removed from neurons, the junk is unlikely to cross through. So biology, through evolution has a catabody that not only selectively kills, but also cut up the remains! Amyloids are misfolded proteins, can occur anywhere, cause amyloidosis and all fixes have the problem of wanted remains. Brain amyloids are called Alzheimer's disease. All get it fast or slow.
3. Genetic damage accumulates in our genes as we age: mutations and epimutations. Practically, both mutations and epimutations ultimately harm us in the same way: by causing abnormal gene expression, whether it’s by increasing or decreasing the amount of a protein encoded by a gene being produced, by altering the conditions under which that production is activated, or by altering the structure and function of the ensuing protein itself. Because of their similar effects, an approach that prevents the negative consequences of these changes in gene expression can be used to make both kinds of damage harmless, despite the fact that the molecular basis of mutations and epimutations are quite different.
4. Cross-link is a common biological problem. A cell produces a lot of junk from many components. All this goes to some lysosome sacs where it is stored cross-linked, and junk is broken by encapsulated strong acids and bases. The structure of junk is a p-space complete i.e. each structure approximates a random cross-link arrangement. Every cell needs to be garbage collected - daughtering duplication does not produce junk-free daughters.
5. Bad cells have to be slain and remnants dispatch in a single step. Cellular ablation achieves that. Catabodies do that. Immune killer cells do it. Blood carries remnants away.
6. Apoptosis is civilized slaying - you raise a signal demanding someone do die. But defective cells ignore the signal! When the immune system is active, it hunts and kills apoptosis ignoring cells, and garbage collection of remnant pieces is performed in kidney organs, etc.
7. The rejuvenation biotechnologies with which most people are most familiar: cell therapy and tissue engineering, the science of growing organs for transplant in an artificial, biodegradable scaffold outside the body. The foundations of this form of medicine lie in the transplantation of organs and tissues that we already use to replace the blood of chemotherapy patients or the kidneys of dialysis patients. However, as most people know, the therapeutic potential of today’s lifesaving transplant-based therapies is severely limited by the limited number of organs and cells available for transplantation. As well, transplanting organs and tissues from one person to another can lead to terrible complications, when the immune system “rejects” and attacks the donated tissue as “foreign.” This immune reaction then needs to be suppressed by lifelong drug administration, impairing the recipient’s resistance to infections and possibly to cancer.
Epilog
The incorporation of Dr. de Grey in Dr. Sinclair is very simple for me, as I already have a hyperfunction extension that may have to be extended more for some more of Dr. de Grey's insights. I am a proud follower of the damage repair paradigm of Dr. de Grey. But I follow a distinct unique view that damage repair is the repair of existing machinery but by replacement by backbox-equal-or better parts and the only reason to restore functionary medicines is no-better parts. In many cases, while the xenoscaffold is possibly injurious before the sale fixup, it is populated by customer cells! Consider CABG bypass of the heart. My different equal interpretation is to ignore current arteries and veins and focus on the bypass blood vessel and their connections. There is no mismatch if the vessels are harvested elsewhere from the patient. There is no problem if the heart itself is a newly grown organ addition!
A hyperfunction takes many parameters and returns many results. Assume that the complete status of the body is parameters. The aging hyperfunction returns a new value of all parameters and several diagnostic values being the overview along various aging dimensions and a Boolean (alive | dead) or bitset integer that also states death state of heart-dead, brain-dead, <organ>dead, <ALCOR>dead, etc.
Body death is the earliest death in any dimension from the many dimensions eroding in parallel. My aging theory contains Professor Sinclair's theory of “information aging” as a small but vital part and is renamed “DNA sub-theory”. A full list derived from me, based on Dr. de Grey, on human anatomy and processes, is in this essay.
Never in above have I bothered to consider evolution in looks – left to worry by the small part of women considered stupid and part of men considered stupid like many actors. Not anymore after a viral fever disease that made me look old and I stupidly circulated them withoutlooking1!. I studied and have started on Hyaluronic acid and Collagen. I am not dependent on looks in any way except proposition lovely women. With de-aging comes age-dependent looks, which is normal. Except that I just woke up after a viral fever and immediately after, you look old. HV fills voids and tightens skin. Likely safe as natural. Inexpensive (relative to NMN and senolytes). Likely independent of the rest of the stack. Sold as HC mix. So definitely part of my stack. If I notice any bad effects, I will stop.
Restored my cap to cover the genetic bald spot.
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