Thursday, October 10, 2013

Wanna live forever ?

Wanna live forever ?

Andre Willers
10 Oct 2013
Synopsis :
First , lose bad genetic habits (epigenetics) . Then train new ones .

Discussion :
1.Read Appendix I . Especially the link . It is safe . But I am not going to copy it all .
2.Essentially , the research shows that genome-wide DNA demethylation occurs with EPO .
3.So , you lose some bad epigenetic habits (est 2/3) , but also the good ones (est 1/3) .
4.Performance will be enhanced , as safety switches has been deactivated .
5.But damage (heart etc) due to overstress is nearly inevitable .
6.PTSD : Obvious . The muscle memory leg of PTSD feedback cycles is disrupted .
7.Stuttering : A hefty shot of EPO should cure this . Epigenetic muscle memory will be lost .
8.After wiping epigenetic memory , the good memories will have to re-established .
9.Errk . I don’t know how to do this .
A goodly part of the immune system (1/9) will be gone with it , as well as certain memory systems .
10 . Immortality :
Genome-wide DNA demethylation means the cells do not apoptose . No old age  .
You can live until an accident kills you . (+-25  000 yrs)
11. But this beats the Hayflick Limit
See Appendix II . Zeroizing the underlying epigenetic errors , sets the Hayflick limit -> infinity .
12.What a surprise . You can live forever , barring accidents . Nobody would want to if full memory is kept , but notice the Epigenetic-memory role in real memory . Really high doses of EPO will scrub memory.
Regards from Midgarde


Appendix I

Genome-wide loss in DNA methylation during erythroid differentiation

The erythroid S phase-dependent switch (Figure 3) is associated with a dramatic increase in the rate of DNA synthesis, apparently exceeding the DNA methylation capacity of the cells and resulting in genome-wide DNA demethylation (Figure 4,5). This global loss in methylation is required for the rapid induction of a subset of erythroid genes that are massively induced during erythropoiesis, including genes required for hemoglobin synthesis. This finding provides the first instance of a genome-wide loss in DNA methylation in normal (non-cancer) somatic cells. Previously, global demethylation was thought to be confined to the pre-implantation embryo and to primordial germ cells. We are investigating the mechanisms responsible for the global loss in DNA methylation, which may aid in understanding global demethylation in other contexts, including cancer and early development.
Using a combined experimental and mathematical modeling approach we found that the death receptor Fas, and its ligand, FasL, are negative regulators of erythropoiesis in the fetus and adult. Further, signaling by Epo and its receptor, EpoR, suppresses expression of the pro-apoptotic Fas, FaL and Bim proteins, and induces the anti-apoptotic Bcl-xL. These Epo-activated survival pathways appear redundant in vitro. However, we found that they each impart unique system-level functions in vivo (Figure 6). Thus, Fas and FasL are unique in that they alone amongst these proteins exert negative autoregulation of erythroblasts within erythropoietic tissue. We showed that this autoregulatory loop stabilizes the erythroid progenitor pool, and in addition, accelerates its stress response.
By contrast, Epo-mediated induction of Bcl-xL is unique in that it undergoes classical adaptation, a dynamic response that is well known in sensory pathways or bacterial chemotaxis. Thus, the acute onset of erythropoietic stress induces a rapid but transient Bcl-xL response that quickly resets, ready to respond afresh to any further change in stress. Adaptation in the Bcl-xL pathway extends the dynamic range of the erythropoietic stress response.

Appendix II
Andre Willers
17 Feb 2011

"How long is a piece of string ?" Anon

Synopsis :
Random Intron sequences between genes get mistaken for telomere chromosome caps at mitosis . Drastic chromosome shortening occurs , with concomitant apoptosis . Old age results .

Discussion :
See "Phene Systems II" Feb 2011

To quote :
"Genes on the outer Heterochromatin string , on activation from the Phene system , unwinds to make the DNA accessible . The chromatin string simultaneously also migrates inward to a transcription factory (presumably triggered by the phene signal) and gets expressed ."

Introns :
The chromatinin string is not magic chewing gum . To stretch like this , lengths between activation markers on the DNA are filled in with random codons , hopefully signifying nothing . But there is a basic problem with Randomness .
See "Problems with randomization" Nov 2010 .
It is not as random as we would wish . Meaning to other systems creep in .

In this case , telomeres for VertebratesHumanmouseXenopus are coded by TTAGGG
These creep in .We calculate how often below .

During mitosis , an intron with this tag will initiate a telomere cap .
Bad things happen then .

For true non-ageing , it would be necessary to elide any intron DNA with a TTAGGG coding .
Present technology can do this . Whether it would be sufficient , needs some further consideration .

Probability of TTAGGG
1,There are 4 bases , which gives 4^6=4096 possibilities .
2,This is one of those little pitfalls of probability . A combination of double , single and triples seemingly gives a higher probability . But there is only one permutation that satisfies the requirement .
thus p = 1/4096 = 0.000244414

Suppose there is a p probability of damage at each mitosis event .
Then the cumulative damage ratio would be Cd= p* n(n+1)/2 , where n is the number of cell divisions . A linear summation .

From "NewTools" Reserves and error arguments we know that for an old system like this 1/3 error ratio would probably render it non-viable .

Thus , we can say 1/3 = p* n(n+1)/2 would solve for n at the Hayflick limit .

Calculation :
1/3 = 1/4096* n(n+1)/2
This gives quadratic equation of form
n^2 + n – 2.71266666667 = 0 …Notice how close the constant is to e = 2.71828. Remember , the ratio 1/3 is also an approximation . The usual tantalizing , delicious things are going on .
n = (-1 +- (1+4*2.7126666)*0.5 ) / 2
n = -1/2 +- 52.06566
n = 51.5866 or -52.58666

This is the Hayflick Limit . (See Appendix B below)
We have thus derived the Hayflick limit for humans from first principles .

Well and good , but what does it mean ?
Such a close fit with the Hayflick limit indicates that random intron generation (and insufficient intron absorption on chromatinin shortening ) is the main driver of the ageing mechanism

What to do ?
1. Increasing telomerase will make things worse .
See Appendix A . The more primitive the organism , the longer the telomere . This indicates more of a sideways gene-material transfers than longevity .

2. iRNA could be used to remove TTAGGG at mitosis .
Promising .

3. I think that an attempt to reverse the directionality of the DNA copying process (from 3 prime to 5 prime or the other way) holds a lot of promise .There are more variables , especially Phosphor . Can do a lot of things with phosphor .

4.Immune system will have to be used , but later on . Not of much use inside cell-nuclei .

5 Phene systems , of course .
Combined with valets .

6 Note that Cytosine has been left out of TTAGGG .
Why ?
These are very old systems .
There must be a very good evolutionary reason .

6.1 Cytosine has been used in quantum computing .

6.2 As cytidine triphosphate (CTP), it can act as a co-factor to enzymes, and can transfer a phosphate to convertadenosine diphosphate(ADP) to adenosine triphosphate (ATP).

6.3 In DNA and RNA, cytosine is paired with guanine. However, it is inherently unstable, and can change into uracil (spontaneous deamination).
(Beware of "spontaneous" DNA changes AW)
This can lead to a point mutation if not repaired by theDNA repair enzymes such as uracil glycosylase, which cleaves a uracil in DNA.

6.4 Cytosine can also be methylated into 5-methylcytosine by an enzyme called DNA methyltransferase or be methylated and hydroxylated to make 5-hydroxymethylcytosine. Active enzymatic deamination of cytosine or 5-methylcytosine by the APOBEC family of cytosine deaminases could have both beneficial and detrimental implications on various cellular processes as well as on organismal evolution.[4] The implications of deamination on 5-hydroxymethylcytosine, on the other hand, remains less understood.

This means Cytosine is part of the Histone System , hence part of the Phene system

Attach it to any or all of the Guanine's in TTAGGG and the problem is solved . But we must still ensure that other G's are not inadvertently activated / deactivated .

Some plants can already do it . Tea (Green tea) . Using the methylization (epigenetic) route .
It can be made much easier with programmed water "Memory of water" Feb 2011

Death :

See "Singularities"

Remember , Death is the Singularity
Old Age is simply the event horizon .

Ask Lady Gaga



Appendix A (from Wiki)
Some known telomere sequencesGroupOrganismTelomeric repeat (5' to 3' toward the end)VertebratesHumanmouseXenopusTTAGGGFilamentous fungiNeurospora crassaTTAGGGSlime mouldsPhysarumDidymiumTTAGGGDictyosteliumAG(1-8)KinetoplastidprotozoaTrypanosomaCrithidiaTTAGGGCiliate protozoaTetrahymenaGlaucomaTTGGGGParameciumTTGGG(T/G)OxytrichaStylonychia,EuplotesTTTTGGGGApicomplexanprotozoaPlasmodiumTTAGGG(T/C)Higher plantsArabidopsis thalianaTTTAGGGGreen algaeChlamydomonasTTTTAGGGInsectsBombyx moriTTAGGRoundwormsAscaris lumbricoidesTTAGGCFission yeastsSchizosaccharomyces pombeTTAC(A)(C)G(1-8)Budding yeastsSaccharomyces cerevisiaeTGTGGGTGTGGTG (from RNA template)
or G(2-3)(TG)(1-6)T (consensus)

Appendix B (from Wiki)
The Hayflick limit was discovered by Leonard Hayflick in 1961,[1] at the Wistar Institute(Philadelphia), when Hayflick demonstrated that a population of normal human fetal cells in a cell culture divide between 40 and 60 times. It then enters a senescence phase (refuting the contention by Alexis Carrel that normal cells are immortal). Each mitosis shortens thetelomeres on the DNA of the cell. Telomere shortening in humans eventually blocks cell division and correlates with aging.[clarification needed] This mechanism appears to prevent genomic instability and the development of cancer.


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