Ageing

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 :
See http://andreswhy.blogspot.com "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 http://andreswhy.blogspot.com "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 VertebratesHuman, mouse, Xenopus 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 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
http://andreswhy.blogspot.com "Memory of water" Feb 2011

Death :

See http://andreswhy.blogspot.com "Singularities"

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

Ask Lady Gaga

Andre

xxxxxxxxxxxxxxxxxxx

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

xxxxxxxxxxxxxxxxxxxxxxxxxx

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.

xxxxxxxxxxxxxxxxxxxxxxxxxx