Fatigue and old age

Fatigue and Old Age
Andre Willers
23 Apr 2012
“Too tired to keep on living , too scared to die” : Old Man River
Synopsis :
Fatigue , old age and fertility are related via quorum mechanisms , using telomeres and prions . We try to find a logical pathway connecting them .
Discussion :
1.Fatigue :
Prof Tim Noakes , a foremost sports scientist (see “Challenging beliefs” , (ISBN 978 1 77022 459 9) 2012 edition) p 328 et al) found that “my brain always wanted me to quit when I had covered about 66 percent of the race distance . I gather that this is not an uncommon response.”
Now see http://andreswhy.blogspot.com “Infinite Probes in Optimization” Jan 2008 and others around then . Repeated in Appendix I for your ease .
Note the arguments about Reserves . In general systems have evolved to keep a reserve of 33 percent . Hence the finding of Noakes . (This result is found everywhere in old evolutionary systems) .
The interesting question : how does the brain-body system “know” at a deep level what the requirements will be ? Noakes gives a strong indication : “What I do know is that since understanding the nature of these regulatory processes in the central governor , I no longer suffer from this specific symptom to quit either in training or racing . Others report the same .”
In other words , there exists a mechanism that releases the Reserve .It is tempting to think that this is a brain thing , but we find it in all undomesticated animals . Note that domesticated horses will run until they die . The Reserve switch has been bred into a permanent “off” position . A definite genetic mechanism exists , associated with aggression and startle-responses .
This points to the amygdala , a notoriously stupid system . It will treat any startlement as a signal to hoard reserves . (Ie if your heart sinks at the thought of a 100 km race , you will experience extreme fatigue after 66 km , even if you are driving a car .)
But how does it work ?
Somewhere along the line neuronal signals have to be translated into chemical signals that the cells and mitochondria understand . Luckily , we have a very good candidate in the Orexin class of neurotransmitters , manufactured in the hypothalamus .
http://en.wikipedia.org/wiki/Orexin
“Orexin, also called hypocretin, is a neurotransmitter that regulates arousal, wakefulness, and appetite.[1] The most common form of narcolepsy, in which the sufferer briefly loses muscle tone (cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.[2]
The brain contains very few cells that produce orexin: in a human brain, about 10,000 to 20,000 neurons[2] in thehypothalamus.[1] However, the axons from these neurons extend throughout the entire brain and spinal cord,[3] where there are also receptors for orexin.”
There is an intimate connection with Melatonin . See Appendix II below .
Briefly , Orexins excite feedback loops , and Melatonin as the ultimate Enforcer curtail these feedbacks .
But in a living , evolutionary organism it does not stay as simple as that .
Examples:
1.An athlete training with low dosages of melatonin will have a significant advantage if he stops using them before the big race. (A pulse of orexins will result)
2.Orexin suppressants should be used sparingly , as there will be a synergistic reaction with normal melatonin cycles .
Still , melatonin remains a useful intervention .

What has this to do with Old Age and Fertility ?
Basically , epigenic and prion mechanisms are have evolved to limit the fertility and longevity of populations . The quorum system , adapted from bacteria , is used extensively .
See Appendix III below for the Fertility Epidemic .
Old age Epidemic :
A prion disrupts the ribosome read from the histone that codes for telomere regeneration . This would be related to the fertility plague prion . We would expect that the fertility plague prion would interfere with the Old Age prion . Thus , from 1704 AD onwards , infected individuals would live longer .
Essentially , from a biochemical viewpoint , the organism just becomes too tired to keep on living .
Interesting asides :
1.Fleming Effect .
We would expect infected humans to become smarter , as neuron-pruning would decrease.
( The pruning mechanism works on the same principles.)
2.Autoimmune diseases and cancers would increase for the same reason . Aberrancies also live longer . Nothing to do with the environment .
3.Diabetes II : very probably a prion disease . Hence it’s epidemiological aspects . Look at the histone coding for orexins .If it is so , an antibody can be manufactured to eliminate Diabetes II causing prions . Not an immediate cure , but a cure as long as you take the antibody . Like gout . (Sigh . The pharma’s will love this .)

“Awake! The spear of Dawn puts the stars to flight! “ Omar Khayam
Andre

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Appendix I
Infinite Probes in Optimization .
Andre Willers
5 Jan 2008

Definitions:
n! = n*(n-1)*(n-2)*(n-3)*…*1

The Euclidean Constant e .
e = (1/1! + 1/2! + 1/3!+ 1/4!… )
=2.178…

I will make it as simple as possible using costs and temporal sequences as examples .

Assume that the elements of a system are identifiable and repetitive .
The rules of Arithmetic can then be applied .

Take any such system . By definition it can then be subdivided indefinitely . Each subdivision of r elements can have r! possible permutations (or states) .

Let there be a CostReserve to cover unknown costs in the failure of any element in a group .

Key Assumption
Let at least one element of each r be Aristotelian False (ie a failure cost item)

The Total cost of failure will be the sum of the cost of failures of the elements.
(ReserveCost) *( (1/1! + 1/2! + 1/3!+ 1/4!… ))= (TotalCost)

Your Reserve times the sum of individual failures = total
This defines the boundary .

This is the optimization equation .

This is equal to
ReserveCost / TotalCost = 1/e ~ 0.37

This means that you should not consider an endeavour where the rate of return is less than 37% . This is the long-term break-even point from a probabilistic viewpoint .

This equation is independent of space or time .

Any society (any at all ) that does not deliver 37%+ returns gets zapped by the chaotic downturns .

Since vested interests always decrease rates of returns , empires rise and fall .

The probe can be used in any infinite series , but care has to be taken to define the terms .



An Interesting corollary :

The alert reader would have noticed that the above is true for when there is always at least one false item per group .
What if there is at least one true item per group ? This is approached as follows:

In trading systems , individual items can be identified . The cost of failure in an individual item is then = 1/ (r!/r) = 1/ (r-1)!
The summation is then
(ReserveCost/Item)*(1*1/1! + 2*1/2! + 3*1/3!+ 4*1/4!… ))= (TotalCost)
(ReserveCost/Item)*(1 + 1 + 1/2!+ 1/3!… ))= (TotalCost)
(ReserveCost/Item) / (TotalCost) = 1/(1+e) ~ 0.27

As can be seen , trading systems will survive the collapse of empires . There is a whole 10% difference favouring traders . Recovery systems will then also favor traders .

This is the underlying reason why Stalinistic Communism failed and Chinese went trader . The VOC and East India Co . are good examples .

Ten percent is just too much .

Ho-ho-ho !
The average between 0.37 and 0.27 is roughly 0.33 . A third .Can you see where this is relevant in any infinite situation where uncertainty rules?

Non-Failure Ratio
A non-failure ratio of (1- 1/3) ~2/3 summated over infinity = (2/3) / (1-2/3) =2 .

This means that any system that can be described or broken up into smaller groups is strongly ordered . Successful subgroups survive by a factor of 2 . This is built into the mathematics of the Universe . Life is one such sub-group , so are particles ,etc . Negative entropy is the rule . Life is everywhere . Positive entropy only holds in the most primitive and earliest systems .

Beautiful!

Quantum and non-quantum systems are the same .

Singularity Points.
27% and 37% are singularity points , as are (100-27)=63% and 53% . SocioEconomic systems destabilize at these points . Regardless whether they are human , alien , japanese , chinese or any other sort of ese .
Any society where more than a third of productive enterprise is spent without engendering new wealth creation is doomed .

Tax rates of more than 27% reduce trade . Tax rates between 27% and 37% will let it limp along . Tax rates over 37% is a disaster waiting to happen . It is that simple , and no amount of pontificating will change the realities of economics .

The tax rate anchored between 0% and 27% will follow a catenary . The optimal will be halfway (12.5%) . This would be the optimal VAT rate . Note that deviations from this (up or down) leads to social unrest . The unrest is not linear , but catenary . In other words , it gets rapidly worse as it approaches the anchor points of 0 or 27 % . This is true of any civilization , human or alien . It is inherent in the mathematics .

These are absolute rates , not relative .

The RepoRate .
The tax on new money . If the reporate plus profits stay away from the singularity points (27% , 37%) there is no problem.

What about undefined realities ? Refer to
http://andreswhy.blogspot.com “Topos:
Note in the definitions above , that as groups are divided by n , and n->infinity , the system approaches undefined “thingies” . Hence , it can be used as a probe into undefined realms .

Marriage:
An interesting corollary is optimizing pairings of two . The theory above says that random pairing will lead to a failure rate of 37% . Observation seems to bear this out .

To optimize : Note and keep track the best features of the first 37/100 daters , then seriously consider the first anybody after that who equals or better the standards of the first 37
This optimizes your chances .

This result has been independently reached in games theory

Note that your body is independently doing this sort of infinite analysis . Hence speed dating , cocktail parties , mingling , etc .

A good algorithm is to speed date at least 50 persons . Do not do this if you cannot handle rejection , since this concentrates years of normal rejection into a few weeks .

A therapeutic mechanism? Sects use this whipsaw mechanism of rejection (by the outside world) and warm acceptance by the sect to create mini-societies .
Hence cold-canvassing . Rejection binds them closer . Any converts are a bonus . Most real converts are made by on-on-one contact .

But that is also the definition of most successful families .

If you are stupid and ugly , and can handle speed dating , you are a better man than I am , Human .

Virtual speed dating .
Analogous to cures for fear of heights , fear of confined spaces , etc . Considerable success has been achieved in reprogramming the amygdala for these and related phobias using virtual reality .

A Virtual Rejection website will make money .
That’s OK if somebody learns from it .
Another way for actresses or avatars to make money .
“I was rejected 1000 times by Lara”
“Balls rejected by Lara TombRaider as not dusty enough.”
The mind boggles .


Andre

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Appendix II
Melatonin and Dinosaurs .
Andre Willers
14 Jun 2011

"Sleep that knits up the ravell'd sleave of care " Shakespeare

Synopsis :
Melatonin ended up in various evolutionary roles because of it's powerful , terminal antioxidant effect . Many neurotransmitters (especially NO classes) can be seen as free radicals . (See Appendix A)
Melatonin is Nature's Terminator . (See Appendix C)

Discussion:
A handy Terminator got roped into being the Enforcer for various feedback systems that had to be kept from repeating .

Examples :

1.Cancers (eg breast , prostate cancers)
Interruption of signaling molecules .

2.Circadian rhythms of the brain (sleep)
Dismantling runaway feedback systems before they corrupt long-term memory irreparably (sense of self) See Appendix C

3.Gut rhythms :
A separate system Melatonin excretion by various cells and bacteria .

4.Bile :
Funnily enough , a separate system . Why ?
Tied to the energy system and things like diabetes .

5.Mitochondria :
A sophisticated auto-governor on rates of activity relative to intra-cell position .
Really simple . Really cool . (Think a steam engine's governor) See Appendix B.

6.Skin
As expected , such a powerful terminal antioxidant will also be on the ramparts against foreign invaders (like in the gut)

7 Immune system
Basically a memory system , with potentially unlimited feedback .
Melatonin will terminate this as well , especially in localized , concentrated doses .
But note the correlation between blue-light and HIV .
Very high-intensity pulses of blue light (484 nanometers) or UV should disable the HIV virus .

Contradictions :
This is only seven usages .There are probably more . The same concentrations of melatonin cannot serve all .
Hence , melatonin receptors evolved to meter and control cellular responses .
As well as dopsin receptors in the visual systems .

Loss of UV Dopsins
About 100 MYA for mammals . Remnants (melanopsins) are still responsible for nervous system entrainment , but some biological adaptability (ie getting melatonin from diet) was lost .
It also means that humans are especially vulnerable to depression of melatonin production by light in the Blue Wavelengths (484 nanometers) . CFL and LED lights .
This means that you should only use blue lights if you want to be alert . The effect is very strong (about 100 times) .
Interesting , this should be able to be hyperreal . Diffraction patterns (as with insect , bird and reptile scales) could give blue-to UV light that the mammalian optical systems will interpret as hyperreal .And hyperactive .

Speculation :
Mammalian loss of these dopsins are thought to be the result of low level of light on the forest floor .
But what if the scaly animals had evolved to use Blue and UV as a weapon ?
It would have reduced melatonin production even in darkness .

Imagine huge , impregnable Dinosaur behemoths with a skin ecology of luminescent bacteria , the light diffracting from their scales into the blue and UV .
A magnificent sight !

Remnants :
Birds with brilliant UV plumages should have DNA of the lumenifages in suppressed state . Or you can do it the hard way from the skins of late-stage dinosaurs .

Light-flash Extinction :
An amusing thought . The extremely bright flashes of the meteors would have burned out the skin ecology of the dinosaurs , the subsequent darkness sending them into a terminal melatonin deep sleep . See FireFall .
This can be tested . Since melatonin is a terminal antioxidant , the breakdown products should be measurable even after 65 MY .

Chickens and flu's
The diseases can be seen as stripped-down versions of skin-symbiotes of the old dinosaurs . The worst thing you can do is subject them to UV Like in brooders . Self-assembly of old sequences will follow . A very old revenge .

What is a poor mammal to do ?
Because of the very many uses of melatonin , there is no single solution .
Sometimes you need more , sometimes less . The trick is to know when .
Also , the sources depend on light (especially blue light or UV) , gut , immune system , brain , pills(slow release or fast release) etc .

The basic principle is that it stops things dead . Slowly or quickly .
There is a tie-in with the sulfur mechanism that is responsible for the immobilization of all molecular cellular activity (concentrations of H2S about 80 ppm)
Melatonin stops the H2S blockage . At extremely low concentrations .
Look at the molecule .

This is a typical life-system . Blockages of blockages of blockages leading to a system with graduated responses .

Too little melatonin , and H2S is not sufficiently blocked and the organism goes into stasis . Sleep .

Evolved into hibernation . The long light periods led to depletion of melatonin , leading to H2S hibernation . Neat .

SAD is a direct consequence . Too much melatonin leads to neurotransmitter depletion (especially serotonin)
A berserker has to generate high levels of neurotransmitters internally .

Take a pill !
As seen above , the system has many variants . Endo- and exo- just to start with . There are adjuvants (valerian is one) . Epigenetic variants are possible , but this system is so basic that I think adjuvants would give better results .

So , take a pill with timing and accompanying chemicals .
Each one should target a separate system .

Ageing
The H2S system freezes things . The melatonin system unfreezes it .Pulsing the system enables living and repairing . Sleep with very carefully metered SO2 will enable a very long life for those interested .

Who wants to live forever ?

Andre

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Appendix A

http://en.wikipedia.org/wiki/Melatonin
"Antioxidant
Besides its function as synchronizer of the biological clock, melatonin also exerts a powerful antioxidant activity. The discovery of melatonin as an antioxidant was made in 1993.[85] In many less complex life forms, this is its only known function.[86] Melatonin is an antioxidantthat can easily cross cell membranes and the blood-brain barrier.[6] Melatonin is a direct scavenger of OH, O2−, and NO.[87] Unlike other antioxidants, melatonin does not undergoredox cycling, the ability of a molecule to undergo reduction and oxidation repeatedly. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants, counterintuitively promoting free radical formation. Melatonin, on the other hand, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.[88] "

Appendix B
" A potential mechanism is that melatonin promotes the recruitment of brown adipose tissue (BAT) as well as enhances its activity.[48] This effect would raise the basal metabolic rate by stimulating thermogenesis, heat generation through uncoupling oxidative phosphorylation in mitochondria."

Appendix C
http://en.wikipedia.org/wiki/Phase_response_curve#Melatonin_PRC

"PRC in neurons
Phase response curve analysis can be used to understand the intrinsic properties and oscillatory behavior of regular-spiking neurons.[8] The neuronal PRCs can be classified as being purely positive (PRC type I) or as having negative parts (PRC type II). Importantly, the PRC type exhibited by a neuron is indicative of its input–output function (excitability) as well as synchronization behavior: networks of PRC type II neurons can synchronize their activity via mutual excitatory connections, but those of PRC type I can not.[9]
Experimental estimation of PRC in living, regular-spiking neurons involves measuring the changes in inter-spike interval in response to a small perturbation, such as a transient pulse of current. Notably, the PRC of a neuron is not fixed but may change when firing frequency[10] or neuromodulatory state of the neuron[11] is changed."
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Appendix III
A Vaccine for Overpopulation
Andre Willers
7 Apr 2012
Synopsis:
A prion disease removed natural epigenetic fertility controls circa 1704 AD . A vaccine is possible to train the immune system to recognize and remove the prion culprit .

Discussion :
See http://andreswhy.blogspot.com “Neanderthal Harbours” Apr 2012
Why a prion ?
Prions work by selectively disrupting the “read” process of the ribosome . Like putting a blank piece of paper in front of the letters to be photocopied . In scrapies and madcow , it is the “END” codon that is elided . The ribosome just keeps on copying proteins . See SciAm and NewScientist . This has a survival value for species in stressed circumstances , but is a bit tough on individuals .
Prions are also highly infectious . See
1.http://blogs.scientificamerican.com/observations/2011/05/19/natural-born-prion-killers-lichens-degrade-mad-cow-related-brain-pathogen/
“What has made prions difficult to control is their infamous durability. Boil water for a few minutes, and all the bacteria and viruses will be gone. Not so for the prion: it will be just fine, reaAs if it weren’t bad enough that deadly prions can survive boiling and radiation, now comes word that aerosolized forms of the pathogen can enter the nose and find their way to the brain, with fatal consequences.dy to infect. How does it fare in a dry heat of 600 degrees C? No problem there, either. How about ionizing radiation? Bring it on.”

2.scientificamerican.com/obseblogs.rvations/2011/01/13/bad-prion-breath-mad-cow-disease-agent-can-infect-via-the-air/
“As if it weren’t bad enough that deadly prions can survive boiling and radiation, now comes word that aerosolized forms of the pathogen can enter the nose and find their way to the brain, with fatal consequences.”


Epigenetics :
There is a sophisticated feedback process at epigenetic level monitoring population-level signals . A development of bacterial quorum-systems . Evolution does not favour Growth-without-limit , otherwise we would not have quorum systems . Remember , bacteria are the majority lifeform . This is the mistake Malthus made .
Malthus :
His Primary assumption was that populations grow to the limit of carrying capacity . This simply was not true before 1704 AD . But when he lived (1766-1874) it was , because the safety catches had been taken off . This happened because of a prion disease from some island off Scotland , rapidly infecting the rest of the world . And no disinfection then or now will work .
Is a vaccine possible ?
Yes. Simple , too .Take the negation of the END codon . The folded prion protein must have the precise lock-on DNA configuration and is thus targetable by tailored anti-bodies . A teensy-weensy problem is to zap only proteins with this configuration . But the heavy lifting has already been done . Neanderthal-derived families with few children should have the requisite molecules . And there are lots of them around the Med .
What does this mean ?
The overpopulation epidemic seems to have run it’s course in the first affected areas (Western Europe , North America) , but not yet in other parts of the world . The creation of a vaccine will cause major political problems . But it will probably share the characteristics of the original disease . Impossible to prevent , and very infectious . It is just the return to the natural state .
Interesting Asides :
1.What does the plants have to say about this ?
Remember , these are not conscious systems . But they are very effective .
Some plants have positive feedback relationship with humans . Grains and especially ones used in weaving . The introduction of woven cloths has always led to a population explosion . The fibres in close contact with the skin leads to positive feedbacks for prions suppressing epigenetic population control . Slow to start , but all plant weaves today encourages fertility .(By definition) . And they all target the same area in the epigenetic system . To find a vaccine , go to the nearest shop and buy any woven material . Look for prions .

2.Oh no !
Whisky . The Scottish Islands in 1704 AD exported mainly people , whisky and wool . All would carry the prions , but whisky the easiest of all . No wonder it was called the “Water of Life” . It was. People who drank it had more children . So , when you look for Person(0) , you know where to look . And look at whisky sales routes for subsequent spread of the infection . I guess this falls under the “some good news and some bad news” classification .

Should humans develop and employ an anti-fertility vaccine ?
They can do it now . But should they ? Well , they are going to do it in any case for short-term advantages , but they should simultaneously develop antidotes to the vaccine .
Places like Italy are already into negative population growth , and if you look at their fashions you can see why . (What! You think plants don’t have fashions ? Good luck with your sex-life . A fashionable fabric by definition promotes the sex-life of it’s partner .)

God’s Mercy
Instead of fashionably going extinct or superhuman , the possible pathways for human futures suddenly un-pinched from a neat two to a messy infinity . For some unfathomable reason the Powers-that-be decided to extend humanity’s term . The pinching-off branches have opened up . (The time-aspects were not predetermined . Think of it as a change in top-down chaotic attractors . You don’t have the terms)
Not my idea . I am but a time-limited pen , rather sourly recording .
Oh well .
Back to long-term planning .
“What God wants , God gets”
Andre
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