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
Andre
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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.
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Appendix II
Ageing.
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 :
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 .
It is not as
random as we would wish . Meaning to other systems creep in .
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 http://andreswhy.blogspot.com
"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
2*4096/3=n^2+n
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
Death :
Remember , Death is the Singularity
Old Age is
simply the event horizon .
Ask Lady
Gaga
Andre
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Appendix A (from Wiki)
Some known telomere
sequencesGroupOrganismTelomeric repeat (5' to 3' toward the end)VertebratesHuman, mouse, XenopusTTAGGGFilamentous fungiNeurospora
crassaTTAGGGSlime
mouldsPhysarum, DidymiumTTAGGGDictyosteliumAG(1-8)KinetoplastidprotozoaTrypanosoma, CrithidiaTTAGGGCiliate protozoaTetrahymena, GlaucomaTTGGGGParameciumTTGGG(T/G)Oxytricha, Stylonychia,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)Saccharomyces castelliiTCTGGGTGCandida glabrataGGGGTCTGGGTGCTGCandida albicansGGTGTACGGATGTCTAACTTCTTCandida tropicalisGGTGTA[C/A]GGATGTCACGATCATTCandida maltosaGGTGTACGGATGCAGACTCGCTTCandida guillermondiiGGTGTACCandida pseudotropicalisGGTGTACGGATTTGATTAGTTATGTKluyveromyces lactisGGTGTACGGATTTGATTAGGTATGT
or G(2-3)(TG)(1-6)T (consensus)Saccharomyces castelliiTCTGGGTGCandida glabrataGGGGTCTGGGTGCTGCandida albicansGGTGTACGGATGTCTAACTTCTTCandida tropicalisGGTGTA[C/A]GGATGTCACGATCATTCandida maltosaGGTGTACGGATGCAGACTCGCTTCandida guillermondiiGGTGTACCandida pseudotropicalisGGTGTACGGATTTGATTAGTTATGTKluyveromyces lactisGGTGTACGGATTTGATTAGGTATGT
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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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