Drug testing

Death, Aging, Rejuvenation (Part 2)


Death. Why it happens? Why do we die? Why do animals die? Why do plants die? What is the need of this? In my opinion mechanism of death was selected during Evolution.

From the position of Darwin's theory of Natural Selection everything, that benefits survival of species and gives advantage in Natural Selection, is preserved in following generations.

Improvements were often left unchanged from the moment of life appearance. Though there could be other ways, certain mechanisms were accidentally selected. These improvements are reproduced in the genome of more complex species. Billions of years ago, according to the theory of evolution, chemicals randomly organized themselves into a self-replicating molecule.

Lightings and UV-radiation helped to create first organic molecules. This phenomenon is reproducible in a lab. The experiments were described in 1950-60.

First self-replicating molecules were probably RNA. First enzymes were probably RNA - enzymes. Then proteins, DNA and more complex lipid molecules and polysaccharide came to the scene.

Death as it is did not exist at the stage of Primeval Soup . Sure some organic molecules were destroyed , some new created. But in general it was still that swirling and bubbling primary broth - quasi alive in our understanding as a mixture of biochemical reactions.

Everything in the evolution was build from the previous blocks selected sometime by accident.

Appearance of lipid membranes allows to compartmentalize the primary broth and create first cells.

At the cellular stage we could already talk about the Death. Cell is destroyed, membrane is broken, everything leaked out. This is the Death.

Content of cell inside lipid membrane is irradiated. Process of crazy molecular swirling is messed up by free radicals irreversibly. This is also signs of Death.

Yet at the cellular stage we cannot talk about Aging. Death at this stage is accidental, not programed.

Organic molecules may age (oxidation, conjugation, etc.) and cell would die. But damaged molecule are repaired or synthesized fresh usually. Hence, no good reason for a single cell organism to age. Irreparable damage from external cause leads to Death, not Aging. This is accidental death. For multicellular organisms, there is a parental organism that ages and eventually dies after next generation is born. For mono-cellular organism, there is parental organism that divides and becomes the next generation. There is no Aging leading to death of parental organism.

Mono-cellular organisms are practically immortal in a right environment.

Mechanism of division was selected during evolution. Cell has volume (3-D). Surface membrane is measured in square units (2-D). Growing beyond limits cause inadequate supply of nutrition from environment. Division solves the problem.

Microbes, bacteria are immortal. Some divide every 20 minutes. In a an hour they multiply 8 times.

Tumour cells divide slower. They are eukaryote. Most aggressive divide once a day. There is no need for Aging.

They would die if you do not feed them. They die when you kill them with undiluted bleach in a flask. Otherwise they grow unstoppable. No aging.

Multicellular organism supposedly has several control mechanisms to prevent excessive growth and division, to kill an extra cell. Apoptosis, programmed death, is used.

Cancer cells often loose the control mechanisms.

A scientist from Yale once pointed out to me that we can not say these cells are immortal. Maybe they divide and parental cell dies. Indeed. We do not follow the fate of every individual cell during experiments. They should give more children cells than parental cells die. Otherwise there would not be the multiplication. It is a possible scenario. We do not follow the fate of individual bacteria as well. Maybe they actually undergo aging.

From the other hand some experiments suggest that new cells contain roughly half of the parent cell after division. So it is not Death or Aging. Next generations contain 1/4, 1/8, 1/16 and so on of the parent cell. Any mechanism that is more complex than simple division would cause disadvantage in evolution and would be quickly eliminated. On the level of mono-cellular organism neither Aging nor Apoptosis make a lot of sense. Though Nature often have hidden reasons.

Flick's phenomenon and telomeres shortening make sense for a multicellular organism. Cells of multicellular organism do age. They stop dividing after 70 divisions or so.

A multi-cell organism has clear cut advantage over a mono-cell.

Why would mechanism of Death selected for multicellular organisms? Scenario could be the following.

Big organism have more advantages compare to smaller one - stability, protection, etc. There are not so many natural enemies for whale or elephant because of their size. Large animals could be brought down by bacteria, viruses, small parasites, and lack of available food. Rare predator attack whale or elephant.

No wonder that evolution was going into the direction of bigger animals - just look at giant bones of dinosaurs and you will feel some appreciation.

Millions years ago not only Dinosaurs but also insects or crustacean were enormous. Cockroaches, spiders or dragon flies with size of one metre (3 feet). Going back in time we find shells of enormous molluscs. Many things imply that bigger animal with unstoppable growth have a lot of advantages compare to small ones. New species often evolve in their size. An example is growth acceleration in humans. Females prefer taller mates that lead to taller children. Shorter plants usually cannot compete with the taller forms in the wild. A short mutant in a patch of tall plants would be shaded out

Mechanism of reproduction was also selected during the evolution. Any new animal, be it a mouse or a human, starts life as a single cell. That cell differentiates and develops into the complete animal. It assures that a rare advantageous variant sequence of DNA will be rapidly propagated by natural selection. It is much easier to reproduce and maybe get some new genes or favourable mutations starting from a single cell than starting from a whole multicellular organism. Functions of most genes will have been optimized by random point mutation and selection in any given species. Signalling between cells during the development process ensure that everything ends up in the right place. Tiny changes in these Signalling processes can have very large effects on the resulting animal. Genome, with at most forty-sixty thousands genes, is able to specify the creation of a human body containing trillions of cells, billions of carefully wired neurons and hundreds of different cell types all amazingly sculpted into organs as diverse as the liver and the brain. This is why mechanism of proliferation of fertilized oocytes was selected.

Hence, having younger (smaller) and older (bigger) animals make sense.

But there is the problem: adult animals (or plants) consume all the nutrition around and there is not much left for next generation.

Then it is why mechanism of Death was selected as a mean for next generation to establish.

Imagine the following:

First, mechanism of proliferation was selected . If mono-cellular organism does not have mechanism of reproduction it does not produce offspring with possible favourable mutations. Let say there are primitive bacteria spontaneously created in primeval soup. Just few of them. They consume nutrition, they live happily, practically immortal but they do not divide. Then set of enzymes appeared during mutations. The set allows bacteria to split. Synthesis of the new set is disadvantageous. It requires additional energy and nutrition. But advantage of splitting allows new mutants immediately overgrow non-proliferating cells. Selection is really cutthroat.

Bacteria growing in a tube represent mini evolution. Any bacteria that fit for the environment are also selected on the ground of simplicity. In a toxic environment (antibiotics) mutant bacteria having a new mechanism of neutralisation would survive. But the more simple bacteria will eventually overgrow complicated ones. Unless complication gives big advantage that outweigh the benefits of simplicity. Another example: HIV virus is very complex compare to some other viruses. But because of the complexity it evades immune response. This is why it is so successful. For humans there was some discussion that hernias are direct problem of erect posture. So erect posture leads to disadvantage. From the other hand erect posture frees the hand, that allows to produce the tools and this gives huge advantage in the survival in natural world by creating possibility to adapt to virtually any condition.

All high animals have just 4 extremities. Obviously it is enough in cutthroat environment. Growing additional couple of extremities will consume much more resources and take much more time, not giving big advantage in speed or protection of an animal. Thus, danger of losing one of the limb is not so big as the danger to not proliferate fast enough.

Bilateral design of majority of animals was chosen at the level of primitive species. Though lower multicellular organisms may have 3-side symmetry or 5-side symmetry like sea stars. Often something chosen in the selection becomes building blocks for higher species. Maybe 5-side symmetrical tiger would be possible but it requires intermediate chain.

The same is true for the mechanism of Death. Once chosen, it is replicated in all higher organisms. It should give an advantage in ultimate species survival. Otherwise it loses sense and species would be wiped out.

So, what is advantage for Death?

Immortal and childless animals are growing and growing. Mutations lead to species producing offsprings. They have disadvantage of been more complex. But advantage of proliferating animals is occupation of vaster areas. They displace immortal and childless species. Now, if proliferating animals are immortal they do not give offsprings enough space or food. Next steps of mutation brought mechanism of programmed death at certain age.

Let consider situation when out of two species one is immortal and producing offsprings, other is mortal with offspring production as well. Mortality looks like an obvious disadvantage in stable environment. Adult organism are more powerful and more protected compare to juvenile.

However, next catastrophe will wipe out all the species altogether. Only some mutants can adopt to new environment. But "mutant" for a multicellular organism imply that the mutation happened when the organism had only one cell (the stage of fertilized oocyte for example). Otherwise it needs precisely the same mutations on the level of several cells - infinitely impossible event.

Thus, any species that had the mechanism to allow next generation to flourish (mechanism of programmed Death) will have advantage. They produce more offspring than immortal species. Death of parents spares the space and nutrition. Immortals can die form accidents only. It is too long for children to expect a vacancy.

Then, having more offspring automatically means having more mutations (by mere number of events). Having more mutations means more probability for adaptation to the new environment.

Immortal multicellular organisms, even if they existed in the past, were quickly wiped out by accidents and overgrown by mortal multicellular organisms.

Again all this is just a hypothesis.

- continued in Part 3

About The Author

Aleksandr Kavokin, MD,PhD




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