84 replies to this topic

[addx]

addx, the central point of your thesis seems to be the belief that senescence is needed for evolution to work properly. You have not given anything to back that up besides your statement that otherwise, young animals would not be able to establish territories, or in the example of male lions, to take the head position in a pride. You believe that superior or more adaptive animals will not be able to survive unless the dominant animals first die off. Is that a fair summation of what you are saying?

Not really, tried to explain it above.

Ageing provides a gene pool purifying mechanism.

As does maturing provide a gene pool limited access mechanism.

These facts make sure that the gene pool evolves rather than degenerates if the population is large enough.

If a gene pool guarantees evolution except in low population circumstances than it is ok to presume that offsprings will be better and kill the parents in time.

Most of evolution theory ignores the "life source" explained above.

Life source is limited. There is an evolutionary pressure to give resources to more fit representers of a species to ensure evolutionary survival - to make sure the species adapt fast enough to avoid extinction from another species. Species increase and decrease their maturing and ageing rates in response to these circumstances. A higher order mechanism.

[adamh]

addx, you have avoided the rest of my post in which I pointed out that planned death or aging, will open the door to other species to take away the resources needed for life. In earlier posts you said this was needed to allow the young to take their place. Now you have come up with a somewhat different thesis

You wrote:

the gene pool needs to regulate time to mature to make sure it gets enough deposits or in other words to make sure its subscribers deposit before a death source gets them but after maturation of the body.

If a "bad behaviour gene" survives development of the body there is nothing stopping it from polluting the gene pool. For example, a gene that causes worse acquiring after maturing would persist indefinitely if the species did not have a death source. The reduced replication this would cause wouldn't extinct the gene from the pool. Such subscribers would still make regular albeit slower deposits and the bad gene might infest the entire population of the gene pool subscribers before a death source pressures it out. So,

an artificial death source is provided through ageing of the mature body. Giving it a time limit for making deposits to the gene pool.

A gene infests the pool if it replicates more often than its replicators die out. In order to reduce this tendency ageing causes artificial timed deaths.

This makes sure that bad genes will be pressured out. Only genes whose ability doesn't impair the life form to make enough deposits to overcome the ageing vs. reproduction balance will spread.

If the gene pool provides steady evolution in this way that also means it is worthwhile to induce death of bodies which will become more and more obsolete relative to new ones being created. It then also makes sense kill the old bodies to allow more life source for new better ones.

Mutations are more often degenerating that beneficial so a gene pool can afford to age its bodies only if its population is large enough to guarantee a beneficial mutation among future generations and enough replicating speed to make up for age related deaths. If this doesn't happen the population and the gene pool will in fact start to degenerate.

Why would life need to program a "death source" to weed out inferior genes? Nature provides lots of stress which can end an individual life as well as a species if it does not adapt. You speak as though the bad gene will replicate without opposition unless the individual is programmed to die. I do not see how programmed death is going to remove bad genes, it will remove good as well as bad genes, not distinguishing between the two. The one thing that does differentiate between adaptive genes and maladaptive genes is the ability to survive in the environment in which it lives. Simply programming the organism to die at a certain age will have no effect on removing bad genes that I can see. Perhaps you could explain it more clearly?

A "bad" or maladaptive gene will be one that by definition lowers the ability of the organism to survive. This in and of itself will weed out bad mutations. If a gene allows the organism to live to maturity and then it can less easily gather resources or avoid death, it will over generations be eliminated just as good genes tend to dominate. A difference of 1% in the ability to do any essential function can be all it takes to cause the laggards to fall behind and be lost while those that have even such a tiny advantage take their places. Not in one or two generations usually, but over time.

What a species tries to do is to become so dominant that no other species can challenge it in its niche. Next step seems to be to differentiate into new species that can take the dominant traits into other ecological niches. Thus, a species becomes a genus, and later a family and perhaps after millions of years, a phylum or other main branch of the tree of life.

I wish you would be more specific about how you believe programmed death gets rid of maladaptive genes in favor of "good" genes or, as you seemed to say in your previous posts, how it allows the young to bring better traits into the species.

[addx]

addx, you have avoided the rest of my post in which I pointed out that planned death or aging, will open the door to other species to take away the resources needed for life. In earlier posts you said this was needed to allow the young to take their place. Now you have come up with a somewhat different thesis

I have claimed previously that ageing imposes a time limit providing a forced selection mechanism in the ramblings before.

Why would life need to program a "death source" to weed out inferior genes? Nature provides lots of stress which can end an individual life as well as a species if it does not adapt. You speak as though the bad gene will replicate without opposition unless the individual is programmed to die. I do not see how programmed death is going to remove bad genes, it will remove good as well as bad genes, not distinguishing between the two. The one thing that does differentiate between adaptive genes and maladaptive genes is the ability to survive in the environment in which it lives. Simply programming the organism to die at a certain age will have no effect on removing bad genes that I can see. Perhaps you could explain it more clearly?

An organism isn't programmed to die so much as it is robbed of repair ability.

1) if it is not robbed of repair ability if will spread its bad genes until violent unrepairable damage or forever.

2) robbing the body of repair ability causing it to increasingly die from natural death sources. meaning selection is still meaningful and the speed of ageing releases new resources and forces bad genes out of the pool faster, thus keeping the pool evolving, not degenerating

3) a bad gene spreads through the population. it will not be weeded out by anything unless the replicators don't recognise it and refuse to mate. there is nothing stopping degeneration of the gene pool through steady mutation(of sexual reproduction) except ageing and maturing. only genes that seriously degenerate will be weeded out in time by natural selection to stop the spread.

And science does think evolution worked in tiny steps. It can go backwards in tiny steps as well. There is more chance of a slightly bad mutation, what forces evolution forward then?

A "bad" or maladaptive gene will be one that by definition lowers the ability of the organism to survive. This in and of itself will weed out bad mutations.

as per point 3 above i slightly disagree.

If a gene allows the organism to live to maturity and then it can less easily gather resources or avoid death, it will over generations be eliminated just as good genes tend to dominate. A difference of 1% in the ability to do any essential function can be all it takes to cause the laggards to fall behind and be lost while those that have even such a tiny advantage take their places. Not in one or two generations usually, but over time.

I beg to differ. Good genes tend to dominate in observed life - which all ages!

Type of evolution of bacteria does not reflect the type of evolution of eukaryotes.

Bacteria seem to mutate at provocation, because its an extinction risk otherwise and it only pays of when threatened extinction.

http://aac.asm.org/c.../44/7/1771.full

Mutation rates can largely change for a given antibiotic depending on its concentration during selection (30). Physiological conditions such as the availability of a given carbon source (27) or, in general, bacterial stress (21, 70) may regulate the mutation rate in bacteria. Furthermore, the existence of mutations that produce mutator phenotypes in bacteria (32,72) and the capability of some antibiotics to increase mutability (37, 61) greatly complicate studies of the effects of population dynamics on the emergence of antibiotic-resistant mutants in bacteria.

The mechanism is regulated with stress of bacteria.

Eukaryotes mutate steadily "on purpose" via sexual reproduction, risking more probable bad mutations at every replication.

What a species tries to do is to become so dominant that no other species can challenge it in its niche. Next step seems to be to differentiate into new species that can take the dominant traits into other ecological niches. Thus, a species becomes a genus, and later a family and perhaps after millions of years, a phylum or other main branch of the tree of life.

The next step I would guess to be an offshoot degeneration (early maturation of digestion track due to stress shortening it? starvation madness? perhaps for mammals triggering some age old carnivorous adaptations) of a carnivorous species under youth starving conditions generated by overpopulation.

I wish you would be more specific about how you believe programmed death gets rid of maladaptive genes in favor of "good" genes or, as you seemed to say in your previous posts, how it allows the young to bring better traits into the species.

Ageing sets a time limit on reproduction of the same genome, thus invariably resulting in reduced spread of its genes.

It takes a large number of replications to provide for a beneficial mutation rather than a bad one.

In order for the good one to spread faster and bad ones spread slower, an ageing limit ensures that good ones will extinct the bad ones by replicating more within that time limit(replicating clean gene population faster than natural + ageing death rate) and bad ones by not replicating more(not replicating faster than the infested populations natural + ageing death rate).

Later this forced selection processes evolves into something even more selective.

In other words, a gene can cause a 30% penalty in replicating ability. This will not be enough to stop it from spreading and soon enough most of the population will have it. After it spreads, another such gene may evolve taking another 30% of the remaining replicating ability just like that. See where I'm getting at?

A gene can be extinct only if the carriers of the bad genes death rate is higher than replication rate. Nothing else. If nature doesn't provide enough incentive to select against it, the gene will degenerate the population. I'm not sure how genetics explain this without ageing? My explanation says that the population stays fit through pruning facilitated by ageing.

Speed of ageing determines the "pruning" speed of bad genes or in other words increases the selection at the cost of population growth inhibition or retardation.

The humans evolving to handle various genetic conditions which in past times caused premature death is causing the spread of bad genes through the human population which is obvious. People are having increasing trouble to handle various immunity and allergy issues. This is all being ascribed to pollutants and life style and whatnot. While in fact these people would die before maturing or early into maturity in past reality and such genes would not persist.

The very essence of the gene pool meaning providing steady forward evolution is enabled by the gene pool cleaning itself through ageing.

Edited by addx, 06 April 2014 - 12:31 AM.

[addx]

Here's an example:

http://anthro.paloma...tic/synth_5.htm

In the Lake Maracaibo region of northwest Venezuela, for instance, there is an extraordinarily high frequency of a severe genetically inherited degenerative nerve disorder known as Huntington's disease. Approximately 150 people in the area during the 1990's had this rare fatal condition andmany others were at high risk for developing it. This disease usually does not strike until early middle age, after most people have had their children. However, Huntington's can occur much earlier. About 10% of its victims develop symptoms when they are younger than 20 years old. There is no cure for this disease, but there has been a test for its genetic marker available since 1993. All of the Lake Maracaibo region Huntington's disease victims trace their ancestry to a woman named Maria Concepción Soto who moved into the area in the19th century. She had an unusually large number of descendants and was therefore the "founder" of what is now a population of about 20,000 people with a high risk of having this unpleasant genetically inherited trait.

[addx]

Think of it like this.

If a species replicates a new generation each season and something kills off the parent generation after that, the genes that provide more ability to survive and create many fit procreating offspring will increase faster in percentage of total species population. Bad genes that cause little ability to survive to mating season or reproduce many fit procreating offspring will decrease faster in percentage of total species population. If the species evolves to reproduce many offspring per season it can afford to sacrifice its entire previous generation for evolutionary purposes of increased selection of superior genes provided by such extreme ageing speed. An example of such family of species are insects which evolved the highest number of most diverse animal species on the planet. Multiphenotyping displayed by ant species(workers, queen, warriors, whatnot) for example is remarkably organised instinctual behaviour incredible to evolve.

Edited by addx, 06 April 2014 - 02:34 AM.

[addx]

Here's with numbers.

If a species of insects has a population of 1 million we can also assume the number is steady, balanced with complicated other factors, but steady, lets say a steady homeostatic period is currently in phase.

Lets say the insects die after mating which many do.

Lets say that each insect provides 100 eggs if it makes it to procreation.

This means that 99 hatched insects will die.

If a mutation causes a 2% drop in performance that means the insect will either produce 98 eggs instead of 100 or the 100 insects produces will have a 2% lesser chance of that one insect that gets to mate being among them.

Since the entire parent population is killed and each parent on average only produces one offspring that means that the 2% less performing offspring will be eliminated in a fixed average number of generations, until the 2% chance difference causes the single bad gened insect not to have a surviving offspring.

The setup described would weed out any drop in genetic performance over time. Increase the ageing limit to 3 mating seasons and allow population growth(new resource) and the 2% penalty gene will start to spread.

Since sexual reproduction reproduces only half of the genes, these numbers can be modified for that but it still stands.

Population of such described insects basically only grows through evolution. Each better gene spreads through the population slowly but steadily as it causes the birth/survival rate to be bigger than death rate and each worse gene is rejected easily because it causes the birth/survival rate to be lesser than death rate.

Edited by addx, 06 April 2014 - 03:15 PM.

[addx]

In general, if the insects had a good selection mechanism they could afford to increase lifespans to support more than 1 reproduction.

It takes luck to generate a good gened insect. So why not keep it around to spread its good genes until a better one appears? So instead of killing the entire population, the species lifespan increases to support raising 10 generations. This way they don't have to reproduce 100 offsprings but only 10 offsprings. 10 generations x 10 offsprings will yield the same number of superior gene mutation chances. And if a bad gene arises only 1 of the 100 offspring gets to replace the father and he is selected as best so a bad gene is eliminated like that, by competing all(or most) the offspring with each other and arriving at a social hierarchy that regulates who gets to feed and breed. This allows less slaughter of bodies for "testing mutations" or simply evolving but requires advanced selection harems etc of reptiles.

Insects do compete but only "in the moment" which provides basic selection level. There is no long term status or possession of females.

Edited by addx, 06 April 2014 - 06:46 PM.

[adamh]

An organism isn't programmed to die so much as it is robbed of repair ability.

1) if it is not robbed of repair ability if will spread its bad genes until violent unrepairable damage or forever.

2) robbing the body of repair ability causing it to increasingly die from natural death sources. meaning selection is still meaningful and the speed of ageing releases new resources and forces bad genes out of the pool faster, thus keeping the pool evolving, not degenerating

3) a bad gene spreads through the population. it will not be weeded out by anything unless the replicators don't recognise it and refuse to mate. there is nothing stopping degeneration of the gene pool through steady mutation(of sexual reproduction) except ageing and maturing. only genes that seriously degenerate will be weeded out in time by natural selection to stop the spread.

#3 is where I think you went wrong. A "bad" gene is by definition one that impairs the ability of the species to thrive and survive. Those bad genes that impair the organism before maturity obviously are self limiting and go no further. The very very few bad mutations that only show up after maturity would be the only ones that have a chance to replicate. If indeed they are maladaptive, then the adults would rapidly die off. Some would reproduce but would not "spread rapidly" as you theorize because of the disadvantage they confer on the animal and because other animals would not want to mate with it since in many cases they would sense the impairment.

Only in a vanishingly small percentage of situations would it be good if they died at a certain age, such as with an alzheimers type disease which does not show up until very late in life. This is the only sort of thing that aging would prevent and it would not stop the animal from reproducing, only limit it a little at the end.

Now lets look at the other side of the coin. Lets say a very good and valuable mutation takes place. Aging means that it will be able to mate a certain number of times and then the source of the good genes is lost forever except for what might be passed on while it lived. If the good gene is not dominant, then it could easily be lost in a small population.

I don't see where losing a little bit of the bad gene is more of a benefit than losing the good gene. At best, its a wash. In order for programmed aging, whether you call it loss of repair or whatever you call it, to be worth the cost of putting it in place, it would have to confer an overwhelming advantage. I don't see that here. By causing many of the individuals to die off you self limit the species and it would take a lot to offset that let alone make it a net positive.

My theory is that the organism starts off with a fresh genome, a young nearly perfect body and over the time span it is attacked from all sides and gradually is worn down. The amazing thing is not that it doesn't go forever, but that it goes as long as it does. Since an aged animal can't reproduce very well there is little incentive for the species to develop longevity genes. Where is the payback for that? It would have to take away from something else and if it just means a doddering animal that can't breed will live a long time, that helps the species not at all.

[addx]

#3 is where I think you went wrong. A "bad" gene is by definition one that impairs the ability of the species to thrive and survive. Those bad genes that impair the organism before maturity obviously are self limiting and go no further. The very very few bad mutations that only show up after maturity would be the only ones that have a chance to replicate. If indeed they are maladaptive, then the adults would rapidly die off. Some would reproduce but would not "spread rapidly" as you theorize because of the disadvantage they confer on the animal and because other animals would not want to mate with it since in many cases they would sense the impairment.

Only in a vanishingly small percentage of situations would it be good if they died at a certain age, such as with an alzheimers type disease which does not show up until very late in life. This is the only sort of thing that aging would prevent and it would not stop the animal from reproducing, only limit it a little at the end.

Now lets look at the other side of the coin. Lets say a very good and valuable mutation takes place. Aging means that it will be able to mate a certain number of times and then the source of the good genes is lost forever except for what might be passed on while it lived. If the good gene is not dominant, then it could easily be lost in a small population.

I don't see where losing a little bit of the bad gene is more of a benefit than losing the good gene. At best, its a wash. In order for programmed aging, whether you call it loss of repair or whatever you call it, to be worth the cost of putting it in place, it would have to confer an overwhelming advantage. I don't see that here. By causing many of the individuals to die off you self limit the species and it would take a lot to offset that let alone make it a net positive.

My theory is that the organism starts off with a fresh genome, a young nearly perfect body and over the time span it is attacked from all sides and gradually is worn down. The amazing thing is not that it doesn't go forever, but that it goes as long as it does. Since an aged animal can't reproduce very well there is little incentive for the species to develop longevity genes. Where is the payback for that? It would have to take away from something else and if it just means a doddering animal that can't breed will live a long time, that helps the species not at all.

How is the animals reproductive ability attacked and worn down? By reproduction? That seems like a reproduction limit. Which is pretty much the essence of ageing.

What's important is the acquiring/avoiding ratio for evolution.

Let's say an animal evolves better repair and self-sustaining mechanisms allowing it to live healthy until violent catastrophic damage/death.

This means animals are selected for avoidance as those who live longer produce more offspring. Acquiring and reproduction becomes a risk of death(going out to get food/mate) and so is pushed out in favor of avoidance and more rarer going out ot get food/reproduce for example. This causes a drop in population growth which is made up by increased longevity. This means the animals also have to have fewer descendants than ageing species who die faster of incraesing weakness to defend from predators or pathogens. This means the number of births and deaths decrease and the population is of the same size.

We can see that evolution is slower because of less births. And selection is more focused on avoidance. Giving birth to more children than allowed by population deaths causes them to starve and mature faster. This will eventually produce a genotype that will be smaller and require less nutrients and such a genotype may infact grow in the population. If the smaller genotype sustains the longevity this will again cause overpopulation as the smaller genotype gives more births and deaths are still the same.

On the other hand, animals that are alive procreate so that means those who live longer spread more of their genes. This means that selection against violent death is most prominent. An animal can afford to sacrifice 10% of reproduction for 20% of better avoidance(20% longer average life time) and this will infact increase their number of offspring at the cost of again slower reproduction. Such a gene will spread nevertheless as it produces more offspring in the long term. This can go on until the animal becomes immortal and basicly never produce offspring (or evolve). The population is still alive and avoidance is 100%(no violent deaths) but they don't reproduce or evolve, are they infact alive? This is something that my text warned about - the balance of acquiring, reproduction and avoidance being important for "self-replication-schema" to survive.

Do you really think evolution could not go that way? Turtles for example have evolved in that direction. Marine turtles lay around 100 of eggs. They start reproduction between only when they at least 15-50 years old. Females sometimes skip laying eggs for a year. Females lay their 100 eggs about 50 times per lifetime and this produces perhaps 2-3 adult reproductive turtles. Females have the ability to carry sperm and avoid mating for a season. They have evolved for avoidance and longevity. The hatchlings require a lot of avoidance to survive so long to maturity. And then the adults need to live long to produce enough offspring to make up.

http://www.marinebio...ton/mtrepro.htm

[addx]

Obviously, marine turtle way of life is an extinction threat.

[addx]

Interesting study.

http://www.newyorker...tism-study.html

So it was no shock when a recent Nature study that clarified the well-established link between paternal age and a child’s risk for autism and schizophrenia got lots of attention.

...

The study, by Kari Stefansson and his team at Decode Genetics, in Iceland, used an elegant application of brute-force genetic sequencing to show that approximately ninety-seven per cent of the difference in the rate of de-novo mutations can be attributed to the age of the father. These new mutations arise during the production of eggs or sperm. Since females are born with a lifetime supply of eggs already in their ovaries, the number of de-novo (or novel) mutations a mother passes down is roughly fifteen, regardless of how old she is. Male sperm-producing cells, on the other hand, are constantly dividing, and as a result, the number of spontaneous mutations increases over time.

Interesting? Maybe ageing is a self-destruct mechanism before too much mutation happens in the reproduction mechanisms?



However back to ageing

This is a quote from wiki: http://en.wikipedia....ution_of_ageing

Repeated again because it seems you're busting my balls and I'm not the only one explaining it like that.

Mitteldorf^[24] proposed a group benefit of a limited life span involving regulation of population dynamics. Populations in nature are subject to boom and bust cycles. Often overpopulation can be punished by famine or by epidemic. Either one could wipe out an entire population. Senescence is a means by which a species can 'take control' of its own death rate, and level out the boom-bust cycles. This story may be more plausible than the Weismann hypothesis as a mechanistic explanation, because it addresses the question of how group selection can be rapid enough to compete with individual selection.

Goldsmith^[28] proposed that in addition to increasing the generation rate and thereby evolution rate a limited life span improves the evolution process by limiting the ability of older individuals to dominate the gene pool. Further, the evolution of characteristics such as intelligence and immunity may specially require a limited life span because otherwise acquired characteristics such as experience or exposure to pathogens would tend to override the selection of the beneficial inheritable characteristic. An older and more experienced but less intelligent animal would have a fitness advantage over a younger more intelligent animal except for the effects of ageing.
Skulachev^[29] has suggested that programmed ageing assists the evolution process by providing a gradually increasing challenge or obstacle to survival and reproduction and therefore enhancing the selection of beneficial characteristics. In this sense ageing would act in a manner similar to that of mating rituals that take the form of contests or trials that must be overcome in order to mate (another individually adverse observation). This suggests an advantage of gradual ageing over sudden death as a means of life span regulation.
Weissmann's 1889 ageing theory was essentially an evolvability theory. Ageing or otherwise purposely limited life span helps evolution by freeing resources for younger, and therefore presumably better adapted individuals.
Yang (2013)'s model^[2] is also based on mechanisms of evolvability. Aging accelerates the accumulation of novel adaptive genes in local populations. However, Yang changed the terminology of "evolvability" into "genetic creativity" throughout his paper to facilitate the understanding of how aging can have a shorter-term benefit than the word "evolvability" would imply.

.....

• Existence of complex programmed death mechanisms exist in semelparous species (e.g. octopus) including hormone signalling, nervous system involvement, etc. If a limited life span is generally useful as predicted by the programmed ageing theories, it would be unusual for an octopus to possess a more complex mechanism for accomplishing that function than a mammal.
• Discovery of "ageing genes" with no other apparent function.
• Caloric restriction effect: reduction of available resources increases life span. This behavior has a plausible group benefit in enhancing the survival of a group under famine conditions and also suggests common control.
• Progeria and Werner syndrome are both single-gene genetic diseases that cause acceleration of many or most symptoms of ageing. The fact that a single gene malfunction can cause similar effects on many different manifestations of ageing suggests a common mechanism.
• Although mammal life spans vary over an approximately 100:1 range, manifestations of ageing (cancer, arthritis, weakness, sensory deficit, etc.) are similar in different species. This suggests that the deterioration mechanisms and corresponding maintenance mechanisms operate over a short period (less than the life span of a short-lived mammal). All the mammals therefore need all the maintenance mechanisms. This suggests that the difference between mammals is in a common control mechanism.
• Life span varies greatly among otherwise very similar species (e.g. different varieties of salmon 3:1, different fish 600:1) suggesting that relatively few genes control life span and that relatively minor changes to genotype could cause major differences in life span—suggests common control mechanism.

....

Problems with programmed aging theories


Contrary to the theory of programmed death by aging, individuals from a single species usually live much longer in a protected (laboratory, domestic, civilized environment) than in their wild (natural) environment, reaching ages that would be otherwise practically impossible. Also, in majority of species there doesn't exist any critical age after which death rates change dramatically as intended by the programmed death by aging theory, but the age-dependence of death rates is very smooth and monotonic. However, as mentioned above, V.P. Skulachev^[33] explained that a process of gradual aging has the advantage of facilitating selection for useful traits by allowing old individuals with a useful trait to live longer. It is also easy to imagine that animals with gradual aging will live longer in a protected environment.
The death rates at extreme old ages start to slow down, which is the opposite of what would be expected if death by aging was programmed. From an individual-selection point of view, having genes that would not result in a programmed death by aging would displace genes that cause programmed death by aging as individuals would produce more offspring in their longer lifespan and they could increase the survival of their offspring by providing longer parental support.^[34]

Now it seems the "problems with programmed ageing theories" are not aware of the increased mutation of older males.

Maybe that's also a part of random senescence, but I'm seriously having issues that the most ancient chemical process of sexual reproduction evolved to be controlled by random senescence. It's just something out of a denial handbook, not reality. The sexual reproduction behavior is the most evolved behavior of all, present among almost all eukaryotes and as such the most important evolutionary target spawning new clades as it evolved. Communication neccessary for sexual reproduction gives rise to "OBLIGATORY sociality". This is the only reason we exist. The only reason anything exists in this world except bacteria. Since this obligatory sociality could never be "pressured out" by any means of evolution or it would kill the species - it evolved to provide more selection. Sexual reproduction is the spark of altruism that spawned life as we know it (except bacteria and viruses).

Groups "evolve" by removing bad members and acquiring good members. All groups, not just animal groups, but bussiness groups as well.

A subscription to such a group is a pledge to improve all the time or be killed or even commit suicide (by a rule of the group that ensures the group evolves - may it necessesitate male-male fights before copulation or simply survival in bad conditions).

The individual is rewarded by "good feelings" for each reproduction. Thus he is motivated to be better to achieve what is neccessary for reproduction relative to group rules. He is also frustrated when unable to do so, the frustration warns him that he's failing to improve.

Edited by addx, 07 April 2014 - 02:04 PM.

[addx]

Ok, i think we've went as far as we can with theorizing.

 

My theory actually expands a lot further than evolution theory per se. I have made concrete statements in this topic about the multilevel relevance of opioids in regards to maturing, ageing. I have explained that they are infact the primary "altruism"/"sacrifice" signallers and they facilitate both corporal and phsycic sacrifice/motivation/growth/reduction.

 

So, lets see what opioids do with regards to what has been said in this thread (and the ones before it).

 

There has been a topic where aged stem cells have been revived by manipulating(inhibiting) a stress pathway namely p38 map K. I have projected that this p38 map k cell degrading is done to the stem cells via kappa opioids.. I had no idea about the URLs I'm about to paste at the time. As have I had no idea that Evolution of aging was aready theorised about in the exact same manner as I have done here.

 

So,

 

http://www.ncbi.nlm....les/PMC2856797/

 

MU AND KAPPA OPIOIDS MODULATE MOUSE EMBRYONIC STEM CELL DERIVED NEURAL PROGENITOR DIFFERENTIATION VIA MAP KINASES

 

 

 

http://www.ncbi.nlm....pubmed/16954126

 

Mu- and kappa-opioids induce the differentiation of embryonic stem cells to neural progenitors.

 

 

 

http://bloodjournal..../118/3/775.full

 

The κ opioid system regulates endothelial cell differentiation and pathfinding in vascular development

 

 

 

So my diletant guessing is amazing so far

 

 

I have also made potshots about longevity, fats and opioids working in tandem. They are related. I have explained that female type is more "avoidance"/survival and male type is more "acquiring". We have seen that females have this MOR-KOR heteromer and can endure more pain and are more KOR oriented. We also know that females grow more fat tissue. We also know that fat metabolism(mitochondria function infact) is caused by calorie restriction and it produces longevity. We know that females live longer. Funny how that all connects nicely. Calorie restriction also induces mania in many bipolars. Lets see how opioids relate to fats then 

 

 

http://www.scienceda...91130121433.htm

 

In the research report, scientists show that foods high in fat and sugar stimulate a known opioid receptor, called the kappa opioid receptor, which plays a role in fat metabolism. When this receptor is stimulated, it causes our bodies to hold on to far more fat than our bodies would do otherwise.

 

 

 

http://www.researchg...fect_of_Ghrelin

 

Hypothalamic Kappa Opioid Receptor Modulates the Orexigenic Effect of Ghrelin.

 

 

 

http://diabetes.diab...54/12/3510.full

 

Resistance to Diet-Induced Obesity in μ-Opioid Receptor–Deficient Mice

 

 

 

http://www.ncbi.nlm....pubmed/19917675

 

kappa-Opioid receptors control the metabolic response to a high-energy diet in mice.

 

 

 

So kappa opioids cause energy accumulation and conservation. They inhibit the function of cells to the level they destroy them. This is also energy conserving. They inhibit stem cell division conserving more energy.

 

Mu opioids do all the oposite, induce proliferation of "acquiring" tissues(muscles), not "avoidance" tissues (adipocytes).

 

 

 

Opioids also profoundly control the immune response as anyone withdrawing from them already knows, but a short URL to give a nice overlook.

 

http://cvi.asm.org/c...nt/7/5/719.full

 

As you can see, kappa opioids also induce anti-cancer mechanisms as cancers are also energy wasters.

 

 

 

 

It goes without saying that opioids are infact the only actually working antidepressant, I don't think I need URLs for that, they actually were used as first antidepressants.

 

Tolerance/addiction is a bitch but opioids take away all types of depression like nothing else. If they only didnt waste the last decades pussyfooting around the taboo "addictive poppy seed" we might have had some better pharmacology.

 

 

Now as said, follow the opioids is what needs to be done.

 

-------------

 

 

Opioids regulate sexual reproduction and everything that evolved on top of it - namely behavior of which I have identified two evolutionary directions

 

Kappa opioids modulate "avoidance" evolutionary direction - in general the female phenotype

 

Mu opioids modulate "acquring" evolutionary direction - in general the male phenotype

 

 

Now the evolutionary directions make sense don't they? Now when I say that ageing causes a shift towards increased "acquring" selection - it actually means shit. Shit that other people never seen or connected.

 

 

We can see how kappa opioids cause increased stem cell differentiation(IMO could be called ageing of the cell - use of the cell) while mu opioids cause proliferation(investment, that shall be used later).

 

Calorie restriction leads to longevity because it activated the avoidance mechanicsm. This causes longer age which means more "avoidance" selection.

 

Calorie restriction during maturing leads to stunted growth.

 

Stress during maturing leads to early onset puberty via too much too early differentiation.

 

Calorie surplus during maturing also causes early onset puberty.

 

These are all modulated by - opioids...there are some slight differences between male and female I think but generaly, I feel like science should seriously get their hands dirty and research all this.

 

The species use "good times" to evolve(recycle faster, stronger selection) rather than cause a boom in population. During bad times they conserve population and energy. Population is the energy reserve of the gene pool.

 

Soooooo......

 

Can I get a high 5?

 

 

 

 

 

 

Edited by addx, 08 April 2014 - 08:13 AM.

[Brett Black]

If a species replicates a new generation each season and something kills off the parent generation after that, the genes that provide more ability to survive and create many fit procreating offspring will increase faster in percentage of total species population.

If the parent had genes that were superior for species survival (when compared to the genes of their offspring) then the death of the parent would actually remove evolutionarily superior genes from the population.

You seem to keep assuming that the offspring always/automatically have evolutionarily superior genes compared to the genes of their parent, but this is not necessarily the case.

An organism isn't programmed to die so much as it is robbed of repair ability.

1) if it is not robbed of repair ability if will spread its bad genes until violent unrepairable damage or forever.

An organism that is able to spread its genes forever is the very apex of "good"
(by most common evolutionary biology perspectives), in fact it could be called "perfect." Why do you think this situation would be bad?

You keep using these subjective value judgements about genes being "good" or "bad" in a way that suggests to me that you have fundamental misunderstandings about evolution.

2) robbing the body of repair ability causing it to increasingly die from natural death sources. meaning selection is still meaningful and the speed of ageing releases new resources and forces bad genes out of the pool faster, thus keeping the pool evolving, not degenerating

But such a scheme would also force good genes out of the gene pool faster too, not just bad genes, so is anything actually gained overall?

3) a bad gene spreads through the population.

A gene that spreads through the population is, by most definitions, not "bad" - the whole "point" of a gene is to spread.

there is nothing stopping degeneration of the gene pool through steady mutation(of sexual reproduction) except ageing and maturing. only genes that seriously degenerate will be weeded out in time by natural selection to stop the spread.

Can you succinctly define what you mean by "degenerate" here?

It takes a large number of replications to provide for a beneficial mutation rather than a bad one.

In order for the good one to spread faster and bad ones spread slower, an ageing limit ensures that good ones will extinct the bad ones by replicating more within that time limit(replicating clean gene population faster than natural + ageing death rate) and bad ones by not replicating more(not replicating faster than the infested populations natural + ageing death rate).

I think the quote above may pinpoint one of your errors. Any gene that spreads fast is, by most definitions, a "good" gene, in evolutionary terms. In fact, any gene that spreads at all is "good." Likewise, genes that don't spread are "bad."

You appear to be imagining that there is some quality or qualities, other than the ability to spread, that makes a gene "good" or "bad" in evolutionary terms. So what do you imagine makes a gene good or bad?

[addx]

You appear to be imagining that there is some quality or qualities, other than the ability to spread, that makes a gene "good" or "bad" in evolutionary terms. So what do you imagine makes a gene good or bad?

 

Since your entire post focuses basicly on this - why do I have different standards for good and bad genes. Yes that is the issue. Ageing removes bad genes - but our standards of bad are different. I have already posted the example but I'll do it again.

 

 

I have explained two poles of "selection" or "evolution". Acquring and avoidance behavior. It may have sound insane or creative, but you have to understand it. It's not insane, it's tangible with opioids as described above.

 

 

The two poles have distinct selection pressures and thus form the main direction of evolution of the species.

 

A factor of acquring selection is the life forms food source (life source as I explained) and the competition for it.   (in the organism mu opioids represent the acquring behavior schema)

 

A factor of avoidance selection is the life forms threats to existance ( death source as I explained it).    (in the organism kappa opioids represent the avoidance behavior schema)

 

 

 

The two pressures come from two different sides of the food chain so they are not the same. This is also important.

 

A life form that imposes a "weak ageing limit" (when the body is grown(mu opioids) it matures(kappa opioids) it is "used"(which "matures" it more - again kappa opioids) and "dumped") causes a shift in selection from avoidance towards acquring and increases evolution speed in that direction artificially. This is because with ageing life forms have a time limit to reproduce, they can't avoid "threats" forever or they'll die without ever replicating. So avoidance is weeded out for acquiring. This is done when the population is facing a growth spurt, good times, good food, no calorie surplus. This reduces the population boom in favour of "investment into evolution".

 

If this did not happen all life forms would adapt for immortality. And we would all be some dead-like spores waiting for that freak occurence of nature that will breathe life into us to procreate for a milisecond and then crawl back into a spore or some shell or whatever, like the turtle.

 

So, that's a bad gene.

 

As said, a gene for 20% increase in longevity with 10% reduction in reproduction speed is, from the standpoint of increasing population, good - so the gene will spread. You determine it is good by your standards, I determine it is usually bad by my standards. (but it in fact depends on the species conditions, if the life source is scarce, it is then infact a good gene).

 

I tell you that each such gene would lead to immortality via dead-like-form and almost no reproduction. Just add 100 of such genes, they're ALL good arent they? They all lead to population increase by simple math. But do they lead to life as we see it? The planet earth can support much livelier depictions of life, no?

 

 

Read the last opioids post and comment, see the avoidance and acquring behavior/action manifested through kappa and mu opioids. I'm not being "creative" here, look at what the two lines of opioids do - opposing each other but also having some same action as they induce behavior. Look at how they grow the body and then kill it. Tell me it's not an ageing mechanism.

 

 

 

 

 

Btw.

 

 

The explanation that senescence exists because there was no purpose to evolution resolving issues of immortality because animals in nature die of violent deaths.

 

They don't, they die of old age weakness which made them killed. Infact if the animals didn't weaken at all,  the older ones would have an experience advantage and would be stronger and stronger as life goes on.

 

Why wouldn't evolution evolve immortality? As depicted above, a gene with 20% increase in "delayed aged-related weakness" would thrive due to the extra reproduction achieved in that extra life span. How come this did not happen?

 

It's a flawed mind experiment that's been taken for truth too long. My mind experiments are flawless

 

 

Edited by addx, 08 April 2014 - 08:59 AM.

[addx]

Infact, it's simple.

 

Opioids govern investment of "life force" depending on its availability. It can be either acquired and invested (growth - mu opioids) or secured and used (avoidance - kappa opioids). Both opioids facilitate reproductive behavior as it is a a complex behavior of male agonism and female antagonism faciliated by phenotyped(via vasopressin-males/oxytocin-females being in the same schema with opioids and affected by sexual hormones, estrogen increasing oxytocin function and testosterone vasopressin function) opioid CNS schemas with the male being the "acquirerer"(attacker of the gene pool) and the female being the "avoider" (guardian of the gene pool). 

 

Why do I make so much sense? It's scaring me. Most of all its scaring me that noone is following this, makes me think I'm insane...

Edited by addx, 08 April 2014 - 11:13 AM.

[addx]

Oh, also forgot, kappa opioid are "cold response" receptors, mu are "warm-response". Prevalence of kappa opioid receptors makes you feel cold, their purpose is to spare energy and they do. Mu opioids make you feel warm. 

 

Turtles who incubated in warmer ground develop into males, turtles who incubated in cold ground into females.

 

Human females on average feel more cold. Store more fat and live longer all thanks to kappa opioid action(it seems depending on conditions kappa either improves functioning by inducing more differentiation or stresses/degrades the cell to death, it seems to depend on arrestin presence, is arrestin leaked when the cell has had it?).

 

Menthol is a kappa opioid agonist. How does that feel?

 

 

 

 

 

Kappa opioids mediate cell death (human epithelial cells)

 

http://www.sciencedi...167488900001075

 

 

Kappa opioids mediate cell survival (heart muscle cells)

 

http://www.kinaseres...p?pmid=14747612

 

 

 

How does that sound for acquiring vs. avoidance? 

 

 

 

More evolution?

 

 

http://books.google....pocytes&f=false

 

and

 

http://www.jneurosci.../11859.full.pdf

 

Kappa opioid receptor modulates fertility gating during energy deprivation.

 

 

 

 

 

 

 

 

 

Edited by addx, 08 April 2014 - 05:33 PM.

[addx]

And now for the kill

 

 

http://www.ncbi.nlm..../pubmed/8391083

 

Ageing also exerts important effects on the density of mu- and kappa-opioid receptors in the brain. The number of hypothalamic mu-opioid receptors was significantly decreased in aged animals; a replacement treatment with testosterone does not reverse this decrease, indicating that the decline of hypothalamic mu receptors and of serum titres of testosterone in old rats are independent phenomena. The number of kappa-opioid receptors in the brain increases in the amygdala and in the thalamus with ageing.

 

 

I did not actually ready any study like this, just the one that said they found more KOR receptors in aged rats spines.  So this is predicted.

 

 

 

 

And, you mentioned alzheimers?

 

 

http://www.researchg...isease_patients

 

 

The putative role of the opioid system in cognitive and memory functions prompted us to search for possible changes in the cohort of the major opioid receptors, mu, delta and kappa, in Alzheimer's disease. The present study examines alterations in opioid receptor levels by quantitative autoradiography. These experiments were carried out on coronal sections of postmortem brains from Alzheimer's disease patients and from aged-matched, dementia-free individuals. Brain sections were labeled with the tritiated forms of mu-, delta- and kappa-opioid ligands; DAMGO ([D-Ala(2),N-Me-Phe(4),Gly-ol(5)]-enkephalin), DPDPE ([D-Pen2,5]-enkephalin) and bremazocine (in the presence of mu- and delta-ligands), respectively. Nonspecific binding was determined in the presence of naloxone (10 microM). Brain areas analyzed were caudate, putamen, amygdaloid complex, hippocampal formation and various cerebral and cerebellar cortices. Image analyses of autoradiographs show, that in comparison to the same areas in control brain, statistically significant reductions in mu-opioid receptor binding occur in the subiculum and hippocampus of Alzheimer's disease brains. Binding of delta-opioid receptors is also decreased in the amygdaloid complex and ventral putamen of Alzheimer's disease brains. In contrast, large increases of kappa-opioid receptor binding are found in the dorsal and ventral putamen as well as in the cerebellar cortex of Alzheimer's disease brains. Levels of mu- delta- and kappa-opioid receptor binding are unaltered in the caudate, parahippocampal gyrus and occipito-temporal gyrus. These results may suggest an involvement of the endogenous opioid system in some of the multitude of effects that accompany this dementia.

 

 

http://www.researchg...s_disease_brain

 

 

Kappa opioid receptor mRNA was present in melanized (possibly dopaminergic) neurons of the substantia nigra and the nucleus paranigralis. On the other hand, Parkinson's disease brains had markedly fewer melanized neurons, as expected, and correspondingly very low or background levels of mRNA for the kappa opioid receptor. However, in some cases, remaining melanized neurons still expressed the receptor mRNA. From these results we suggest that dopaminergic neurons in the human substantia nigra and the nucleus paranigralis synthesize kappa opioid receptors and express them in their perikarya and their terminal regions. The kappa opioid receptor expressed in the melanized neurons may play a role in the normal function of dopaminergic systems and possibly in the etiology of Parkinson's disease.

 

 

I also do believe opioids have this effect on all animal life since dawn of evolution. Two distinct behaviour schemas as explained, sharpened by eons of two-sided evolution - yin and yang.

 

 

So, can I get a high 5?

 

Especially since being the only person here that is not looking for immortality

 

 

Now the only way this can be explained is that MOR and KOR are markers of cellular senescence. But when considering their functions, just the ones I listed here and I'm sure there are many more, it seems like a seriously ridiculous thing to conclude.

 

 

 

 

Edited by addx, 08 April 2014 - 06:15 PM.

[addx]

http://onlinelibrary...0752.x/abstract

 

Six normal young men and 10 elderly men with no endocrinological diseases volunteered for the present study. In young men, plasma LH showed a biphasic increase in response to naloxone and plasma LH level during naloxone treatment was significantly higher than the mean of pre-naloxone control levels. In contrast, plasma LH in elderly men was not affected by naloxone.

....

These data suggest (1) that the hypothalamic opioidergic tone is reduced in elderly men and (2) that the primary testicular insufficiency with the advance of age may play a major role in the decline of the hypothalamic opioidergic tone in elderly men.

 

Conclusion (1) is right, conclusion (2) is wrong. As we've seen from the study on rats above:

 

"a replacement treatment with testosterone does not reverse this decrease, indicating that the decline of hypothalamic mu receptors and of serum titres of testosterone in old rats are independent phenomena."

Edited by addx, 08 April 2014 - 07:02 PM.

[addx]

Oh yea, we saw that kappa opioids kill epithelial cells. 

 

http://www.plosone.o...al.pone.0042616

 

Mu opioid does the opposite

 

 

 

We have seen that kappa opioids rescue heart muscle cells

 

 

http://www.ncbi.nlm....pubmed/12198322

 

Mu opioid does the opposite

 

 

 

So, how come mu and kappa opioids across all levels of the body facilitate the "dynamic evolutionary response" in dual fashion as I described it in my ramblings? How come all these functions match exactly to evolutionary ideas of growth and survival for each species since dawn of evolution?

 

The mechanism that they control are essentialy ageing mechanisms, but they only modulate them. I'm sure there's special proteins that timely develop the body and these could probably be used to regenerate it, in combination with opioids. Opioids themselves should be studied to elucidate our function in fact. Since people have started thinking life is meaningless, maybe if they get it written in black and white what a person should do - maybe they'll finally believe it.

 

 

 

 

 

 

 

[addx]

http://www.the-scien...a-in-Sperm-RNA/


Traces of Trauma in Sperm RNA

A mouse study shows that molecular remnants of early-life stress can be passed on to future generations.

----


It's a bit too big to quote but all in all they proven that stressed male mice passed on at least some of their "stress adaptations" acquired through their own maturation to their offspring via RNA in sperm.

[Vardarac]

It seems like your theory as far as opioid receptor profile changing as a form of and driver of aging would be very easy to directly test, don't you think?

[addx]

It seems like your theory as far as opioid receptor profile changing as a form of and driver of aging would be very easy to directly test, don't you think?

After some more elucidating of opioid receptor function and how it combines with other chemicals for different effects, yes, it should be. Some effects are easily testable even now, but not the whole story.

I presume you would intend to produce immortality by interfering with opioids somehow. This would be a very complex undertaking and it would take a very good understanding of all opioidergic functions to know how to manipulate the body into immortality. Even so, opioids govern the *dynamic* response of maturing and aging. There is mechanisms that govern long term timing of proteins that guide growth and such mechanisms are probably also again dynamically modulated by opioids. It's complex to control but can be easy to understand. There's also something else in the combination - arrestins seem to be quite important in modulating opioid receptor function, I have not yet understood how they function. So, I do not think opioids generate all aging or maturation, on the contrary they just modulate it. Lack of opioids receptor function will not rescue or promote aging or inhibit or promote maturing, it will just make them less or not responsive/adaptive to stimulus. I am claiming that maturing and aging itself is a purposeful(but complex) mechanism or behavior of the zygote. I am claiming that opioids facilitate the dynamic modulation of the same mechanism in response to detected evolutionary relevant conditions.

I am claiming that understanding of aging mechanisms can be reached via purposeful research of opioidergic pathways as they respond dynamically to control maturing/aging mechanisms. If we figure out how they do it or what they do we can work our way to elucidating the entire truth. It would be interesting for starters to manipulate opioidergic pathways during phases of maturation(of rats ) to see what can be done. "Proper"/"efficient" maturation will probably aid life span but even insight would be valuable. Then we can see if opioids can be used localy to restore failing organs when failure is obvious or to restore failing brains. It seems to be a complex interaction as an organ that aids survival(heart muscle) will be kept alive by kappa opioids while at the same time an organ that is not that relevant to survival(hair follicles for example) will be killed by kappa opioids or something to that extent. Keeping a constant anti-aging opioidergic "coctail" in the blood to remove all aging does not seem viable to me at this point.


The ability of kappa opioid antagonists to reverse learned helplessness(depression) is monumental in psychiatry IMO. It is monumental because it never results in appearance positive symptoms. For example amphetamines might mask depression through activity/motivation that hides/overrides it rather than cures it so giving a larger dose causes positive symptoms(overactivity/motivation) that can no longer be called anti-depressant but infact pro-euphorical/maniacal. Kappa antagonists remove negative/blockages like learned helplessness and no dose produces increased activity or mania or descreased activity such as sedation. So, one can conclude that we have finaly hit the right "axis". Kappa opioid fundamental involvement in addiction/tolerance also shows that this is "the axis".

It is obvious that a mood is a result of combining two distinct axis. Good mood and bad mood are two distinct axis that compare(compete) rather than a single axis with good on the left side and bad on the right side.
This dual axis "setup" is typical for *everything* in the body and mind. And the duality can essentially be described as growth-investment vs. survival-use and the opioids manifest the dynamic response along those two axis on all levels perfectly split to mu-opioids facilitating growth-investment and kappa opioids facilitating survival-use in response to evolutionary recognized factors.

Given the URLs I listed showing the dynamic(responsive to experience) and dual(growth-investment vs. survival-use) effect of opioids on both aging and maturation of both body(tissue) and mind(memory-behavior schemas) I do believe I produce much "sensible direction" for medical research. Not just for research, but for finally understanding it all, putting it all together.

Edited by addx, 17 April 2014 - 01:58 PM.

[addx]

Some more opioid functions

http://www.researchg...ct_ligated_rats

This is the first study to demonstrate that administration of an opioid antagonist prevents the development of hepatic fibrosis in cirrhosis. Opioids can influence liver fibrogenesis directly via the effect on HSCs and regulation of the redox sensitive mechanisms in the liver.





What most of you are doubting here, opioids are the only neurotransmitters to regulate tissue growth, differentiation and function among all their other function. There is no other nervous system "mechanism" that does this so directly. Opioids manage cell proliferation and function for all tissues that I've encountered.

Here's lungs.

http://www.plosone.o...al.pone.0091577

The Mu Opioid Receptor Promotes Opioid and Growth Factor-Induced Proliferation, Migration and Epithelial Mesenchymal Transition (EMT) in Human Lung Cancer




http://www.researchg...loma_LP-1_cells

Reduction of cell proliferation and potentiation of Fas-induced apoptosis by the selective kappa-opioid receptor agonist U50 488 in the multiple myeloma LP-1 cells.




http://www.nature.co...l/5700634a.html

With the discovery that defined epithelial-cell populations in mammalian skin itself generate endogenous opioids, such as beta-endorphin (Slominski et al., 1992), and use them to modulate multiple different functions (for example, control of hair growth and pigmentation (Furkert et al., 1997; Tobin and Kauser, 2005)), and that wound healing and differentiation in mice are also opioid receptor-regulated phenomena (Bigliardi-Qi et al., 2006), one cannot but consider the skin a "habitual opioid user."


I think I did hint at balding as well.

[Vardarac]

Correct me if I'm wrong, but it seems that you are saying that mu opioid receptor activity seems to encourage growth, while kappa opioid receptor activity seems to inhibit it.

 

What do you see as the specific relationship of these activities to increased frailty and disease with age? How do you see these activities interacting with certain proposed forms of regenerative medicine like those put by SRF, like tissue engineering (putting young tissue in an old body) or genetic augmentation/modifcation (inserting new genes; attempting to reverse changes to expression profiles)?

Edited by Vardarac, 20 April 2014 - 04:35 PM.

[addx]

Correct me if I'm wrong, but it seems that you are saying that mu opioid receptor activity seems to encourage growth, while kappa opioid receptor activity seems to inhibit it.
 
What do you see as the specific relationship of these activities to increased frailty and disease with age? How do you see these activities interacting with certain proposed forms of regenerative medicine like those put by SRF, like tissue engineering (putting young tissue in an old body) or genetic augmentation/modifcation (inserting new genes; attempting to reverse changes to expression profiles)?

I'd say, for the direction you're trying to take the discussion to, it would be perhaps more appropriate to say that mu opioid modulates "investment" into the future(growth and reproduction) while kappa opioid modulates "spending" in the now(differentiation and rationing resources). Depending on the tissue type this may not be that translatable into growth/differentiation of cells as some tissue types whole purpose is investment and others spending.

As said, they are to be considered "investments" and "spending" from the standpoint of evolution, not the individual, the triggers were crafted by evolution, not by an individual. While in most situations interest of the individual is in line with the interest of evolution, it also often isn't so one must lose track of this because one then gets lost explaining altruism and its evolutionary path.

As said, I believe opioids govern most of these activities for "evolutionary purposes" dynamically. Elucidating how they work should shed more light on intracellular signalling in relation to organism wide signalling in terms of maturing and ageing.

Someone opened a thread showing that stem cells are revived by inhibiting the p38 MAP kinase within stem cells from old rats. The same kinase is activated normally by kappa opioids. So, if we followed the opioids(in the sense that I explained they work) we would have found the way to revive stem cells through it. The way has been found nevertheless, but wouldn't it have been nice if the finding confirmed a bigger picture that makes sense. This way it seems the finding just produced yet another piece of a puzzle.

When I read the stem cell thread I immediately guess that opioids do it, and I could project that I would find them modulating development/maturing as well, as they do, via the same mechanisms.

http://www.ncbi.nlm....les/PMC2856797/
 

By administering selective inhibitors, we found that opioid inhibition of NP-derived astrogenesis was driven via extracellular-signal regulated kinase (ERK), while the p38 MAP kinase pathway was implicated in opioid attenuation of neurogenesis.

I have also guessed that kappa opioids cause "sustained stress" somewhere in this thread or the stem cell thread and that when such stem cells are implanted in a young body the nervous system does not know this and does not revive them just for fun.

http://relief.unboun..._in_astrocytes_

 

By this cross-talk, opioids may impact neural development and plasticity among other basic neurobiological processes in vivo. The mu agonist, [D-ala2,mephe4,glyol5]enkephalin (DAMGO), induces a transient stimulation of ERK phosphorylation, whereas kappa agonist, U69,593, engenders sustained ERK activation. Here we demonstrate that acute U69,593 and DAMGO stimulate ERK phosphorylation by utilization of different secondary messengers and protein kinase C (PKC) isoforms upstream of the growth factor pathway.

And I've been guessing these things when provoked by threads like that of stem cells.

I do think elucidating opioids will prove to be very important in tissue regeneration and regrowth, especially nervous tissue, which seems most important, at least to me. There is most proof for nervous tissue in relation to opioids, it might not modulate so much growth of other tissues directly, but indirectly by modulating the nervous network within/operating the tissue. The most "medicine and immortality challenging" ageing disease is in fact of obvious nervous system origin like alzheimers and parkinsons. Other disease could perhaps even be handled by replacing organs with devices, transplants and maybe special pharmacology and whatnot, but nervous system we can not replace and it does not repair itself ever basically since it matures. So the nervous system should be the primary focus of immortality research. And in that sense, opioids are the main obvious force that NORMALLY are able and are in charge of governing maturing/ageing of neuronal cells. This is beyond doubt. So, do I have a point?

If we know as much on opioidergic signalling as we did on dopaminergic and serotonergic, we'd be much better off talking about this now.

Edited by addx, 20 April 2014 - 05:31 PM.