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WHY DO WE AGE?
After passing certain age, our body begins to debilitate irremediably, until some day in inexorable way, it happens the death. Why? Many theories were developed to explain this fact, which affects to us so deeply, and that at same time appears to be so obvious and fatalistic (see 1).
Perhaps the answer to this question is much simpler that it seems to be, it could be closed into a phrase of philosophical content: "IT'S IMPOSSIBLE TO TEACH WHAT IT IS NOT KNOWN".
We are the product from our parent's genetic data, and this single information is able to show our bodies the way to follow until the reproductive age, when we reach the maximum physical and sexual vigor. After this climax (something between 14 to 18 years old), our genes begin to follow a footpath of chaos and misinformation, until the death happens many years after.
This text is written by a amateur in Biology, targeted also to non expert people, and therefore, it will not have enough scientific background to respond many questions. Anyway, it is a readable text based on knowledge of reliable sources (most of the references come from Scientific American magazine). It is possible that the ideas here stated be widely known and disclosed in academic circles, anyway, they appears not to be easily available for common readers, so the present work will try to cover this lacking.
LOGIC EXPLANATIONS FOR AGING
In December 2004, an interesting scientific documentary about human body from London BBC appeared in Brazil's 'TV Cultura'. One of the chapters of that documentary was about aging process in our bodies. The best and more prominent scientists of the world displayed interesting theories to explain the fact, as well as the possible solutions to dimish their effects, or to revert it completely in some future.
Scientific explanations for aging are most based on observations of objects which surround us, which are deteriorated throughout the time. It arises therefore the natural idea that any complex engine, like a person, an automobile or a concrete bridge, tends to 'age' and deteriorate as the time passes.
The first explanation presented in that interesting TV program, is based in the deterioración of cellular copies throughout lifetime. The second explanation, in the deterioración caused by oxidation, since our organism absorbs and uses this active chemical element during all his life. The same explanations are present also in (1).
This work will try to show that both explanations proposed in the BBC program for aging, as well as those appearing in (1), are not correct, and that aging process has nothing to do with time (time interval from birth), with cellular copies, or oxidation process, but only with LACKING OF INFORMATION that our organism suffers at some point in our lives.
SINGLE ORGANISMS NEVER AGE NOR DIE
To explain in detail this central idea, we will use analogies with simple situations, which are easily understood by common reader. Initially, an analogy will be used to explain how the multicellular beings are developed. It is important to make this distinction, since (unlike multicellular ones) the unicellular beings, (bacteria), never age nor 'die'. On the contrary, when they arrive to certain age, they just divide in two new perfectly conserved and identicas bodies.
It is possible to destroy individually some of them (penicillin does it), but even so, they do not know aging process, and the bacterium which originated this one, or even, the previous and previous one, continues surviving like copies on their descendants, in form of genetic information.
From here, we conclude that aging and death can be applied only to the so called 'multicellulars' beings, composed of billions or trillons of tiny 'cells'. Among these beings, obviously, are we, the humans.
And here our first analogy begins. What is a multicellular being?
Understanding how the multicellular organisms developed throughout the biological evolution, will help to understand the aging process, and what 'death' means for them.
DIVIDING TO CONQUER
600 million years ago, multicellular organisms didn't exist on planet Earth. In a so called 'Cambrian period', approximately 550 million years back, were created the first of these beings, like a natural extension of bacterial colonies. In this way appeared simple multicell organisms like flatworms, equinoderms and others, which form the origin of all complex organisms until today (see 2).
To understand their appearance on Earth, it is important first to notice that there is a powerful and constant force in nature, which directs all the dynamic processes toward 'dividing to conquer' strategy.
Do you remember Henry Ford, the clever USA car builder from beginning XX century ? Ford became famous (among another things) because he applied a production system called 'serial assembly' for manufacturing automobiles. Many people think Ford discovered something new and revolutionary, but it is easy to see that Ford just implemented something that nature itself performs since life appeared on planet earth, thousands of million years ago.
In this process, each worker of the factory dedicates itself to perform an unique task, well finished, in the minimum possible time within a called 'assembly line'. The resulting is that the whole factory saves time, quality and price on its products. This idea made Ford a very rich man on his time. If every worker of the factory was obliged to complete the car from beginning to end, it would delay a lot, it would have an inferior quality, and it would be enormously expensive.
So, the same thing happened to bacterial colonies. Instead of every bacterium to make all the work of obtaining and transforming food into energy from environment, colonies began to divide tasks and optimize their production processes, leading every one of their members to specialize in certain tasks, like workers on Ford factories. Some specialized in digesting foods, others in obtaining and processing oxygen, others in transporting it, transmitting information and so. They were born thus different 'organs' within a 'body', lungs, blood, nerves, leaves, roots and so, and as a result, the system gained in efficiency and economy.
Trillions of bacteria, now working altogether, were able to process and extract energy from environment with extraordinary sophistication, at speeds never seen before, for their own benefit. There were born 'multicell' bodies, formed by zillione of bacteria, so integrated and tightened with the others, that give us the impression to form an unique and undivisible being, like Roman centuries marching altogether the same compass. This unicity is an illusion, and in this illusion resides the secret of aging and 'death'.
The bacteria itself, taken in individual form, are also a set of processing systems very organized at atomic level, with specialized subsystems and 'organs'. But this matter escapes to our context.
The same force that lead to division/especialización in the unicellular realm, also operated (and continues to do it) on all alive beings. Yet in a species it is observed with great realism: the insects. Old isolated larvae born from same mother zillions ago, now joined in beehives, anthills and other types of association, where each member specialized in certain tasks, optimizing greately the work of obtaining energy from environment. It could be considered beehives or anthills like 'beings', instead considering each one of the isolated insects like alive beings. Previous 'mother' now became 'queen' and the only reproductive organ of the beehive, whereas others insects became soldiers, workers or drones.
Because these facts, we say that 'dividing to conquer' is an inexorable force that guides destiny of alive beings from the primordy of the creation.
We know there are tasks that only can be executed by organized teams. This apply wery well to companies, military strategy and games. Only when every element of the group performs a part integrated to the total work, some given objective can be obtained. Soccer is a good example of it, since the goals are product of divided collective effort from all the members in the team. Whether every player, individually, ran on the field without link with the others, just kicking the ball towards front, probably the result for this 'team' would be disastrous. The players need to think strategies and combine kicks to optimize goals.
Nature also discovered this principle (by trial and error), throughout thousands of million years, since it constitutes an evolutionary advantage. Only the colonies better organized and with efficient communication system were able to execute tasks of increasing complexity, and this lead finally to the consolidation of multicellular animals and vegetables from bacterial colonies.
If unicellular life in some planet of the universe exists, surely this life will also evolve toward multicellular but complex organisms, whenever there is sufficient time for it. On the same way that members of any organism (being it a colony of insects, a city like New York or a herd of wolves) always will tray to specialize and differentiate the tasks between their members to increase the total efficiency.
MIRACULOUS CHEMICAL SWITCHES GUIDE TO US
We stated that multicellular beings are a foreseeable continuation of bacterial colonies, and this is easy to verify. Every day TV shows that the human body forms first like an only ovum that is divided in two, in four, in eight, 16, 32, and so on until forming the complete organism. There is no fundamental difference here with the fact that a bacterium in a culture will also divide in two, four, eight, 16, 32 etc. until filling all the space and exhausting the resources available in their surroundings.
The only difference on both cases, is that for multicellular organisms the cells communicate in each successive division in a very sophisticated form, whereas the unicellular ones do not communicate, or at last will do it in rudimentary form, so each bacterium will end up single and isolated in environment, having to survive by its own means (see 3 and 4). In the case of multicellular organisms, they will finish tied to the others, now with the name of 'cells', every one executing a different task to form a set that in its external appearance gives the impression of being something unique and indivisible.
Whenever a cell is divided to form two new ones (mitosis, see 5), it sends a message to their 'off-springs' (the two copies resulting of division) in the form of 'genetic activators' (see 6), 'intrones' (see 7) and other kind of codified proteins, which will guide these new cells to form the different organs and functions of the system in some future. The genetic activators are like the switches in our bedrooms, when 'on' they will activate some genes, when 'off' will deactivate them. These miraculous chemical switches set on/off groups of genes as the cells are divided in our bodies, and this game of switching genes, at the end, will say how to form the heart, blood, muscles, nerves and other organs throughout the time.
The activators are proteins that contain simple messages, sent by 'gender' and soon captured by both 'children' product of cellular division, in an endless chain during all life of the multicellular organism. They cause cells undergo small transformations in their behaviour as they are unfolded.
Those fundamental cells which still did not receive messages, are known as 'stem cells', since they can become any organ of the body as they are unfolded, according the genetic activators they will receive (see 8). Scientists are quickly learning to manipulate these wonderful chemical keys.
The process itself is relatively simple, and about the reason why it works this way, it could be be resumed by saying that the information necessary to form an organism, was accumulated and compressed by trials and errors throughout thousands of million years of evolution, after life evolved on the Earth. This information was stored naturally in a complicated proteinic network that expands throughout all the life of the organism, like a sophisticaded fireworks.
LIFE AS FIREWORKS
The birth and development of a multicellular being, can be very well compared with the explosion of a sophisticated fireworks, formed by several stages, with different plays of colourfull lights throughout the time.
Imagine that after sending the firecracker upwards, an engine initiates several smaller explosions and detonations, forming a game of lights and colors in the space. In turning, these detonations will give power again to another set of lights, and soon to others, until the energy of the powder finishes and the spectacle of lights is extinguished.
This is (more or less) what happens to multicellular organisms. From the moment of the conception (the first ovum), it will guide the following cells (result of divisions), by means of genetic activators like an unfolded fireworks, until the end, when trillonss of descendants will occupy an defined place within the called 'being' spectacle. This development 'by estages' will continue during all life of the organism, from the conception, passing through 'birth' to its death.
DETERIORACION OF SUCCESSIVE COPIES
Turning to the BBC's TV program mentioned at the beginning, lets review the first explanation for aging that the scientists offer to us. This explanation is based on the well-known principle that, whenever we make information copies of any kind, it always will be enviromental noise to corrupt copies, and this noise will cause that copies become less sharper and of poor quality.
It is easy to verify this, because when copying a musical tape to another one (nondigital), and repeating this process to another and another, each copy will loss clearness (high frequencies disappearing etc.), because the statics charges, noise from machine recorder itself and other sources, will mix with the original sound of the tape.
The BBC program successively demonstrated this fact using a videotape copied time and time again, until losing all its image in a videorecorder. Using the same principle, many scientists think that the aging process happens because, when cells divide (copies of the previous hroughout the time), they loose quality or 'brightness', and the organism like a whole (formed by trillons of them), begins to age and deteriorate itself.
Nevertheless, there are many facts to contradict this point of view, and one of them is the cloning of alive beings. If cells become increasily deteriorated with successive copies, how to explain that a new and young individual from cells of old individuals can be obtained?. There are cloning cases from animals who died naturally by aging (cats and dogs), even so, owners obtained 'copies' of them by cloning, again young and healthy with all their qualities. (there are companies dedicated nowadays to this task).
This means that cells from the 'old' individuals remain in perfect state, so perfect, that they can integrally reproduce a new young and healthy individual like magic, so not having suffered any proocess of deterioración throughout the life.
The other aspect that contradicts this explanation, arises because a multicellular organism, in its first estages, instead aging and aweaking, it will fortify and turn more healthful on time, until arriving at the reproductive age, (known as the age of greater physical and sexual vigor) a return point from which begins to debilitate. So why the cells would go to copy themselves without defects in this first stage, and only later would begin to display defects in successive copies? There is no explanation for this phenomenon, what leads us to conclude that, in spite of introducing errors in successive cellular copies, they are not strong enough to produce the process known like 'aging', and aven more, it is possible that self-corrective mechanisms even exist for these defects.
The following explanation presented by scientists, known like 'oxidation', also has a great appeal, since this process is the one which 'ages' all the engines and tools we know. It is enough to leave a car for some months at moisture, and soon we will notice that it begins to 'age', by displaying spots of oxidize here and there. The same will happen to TV sets, computers or any other equipment exposed to the atmosphere. Oxygen is an atom (sometimes in form of molecule) very active. It cannot remain in pure state on nature. Oxigen always will try to glue chemically to other elements altering its basic composition. With iron it forms oxides, with hydrogen form water, and so on.
If we assume that human body (or any other animal), is a sophisticated engine of great complexity absorbing throughout lifetime oxygen by breathing to obtain energy, it is quite logical to think that this oxygen could be the main cause for aging, on the same way that it deteriorates a car or a bridge throughout the years by oxidation process. This idea carried to many suppositions, one of them known as 'free radicals' theory. Fighting the free radicals, product of the oxidation, we could perhaps slow down aging in the alive beings.
In spite of the attractiveness that this idea offers, it faces again a well-known fact: from the birth to reproductive epoch, multicellular organisms not only won't age, but it gradually will become stronger and powerful, and only will begin to debilitate and age from that point.
This can better be observed in other animals, like insects, where they die almost right away after having procreated, as if it were the only and fundamental task for which they were generated. There are insects that born and grow during some weeks, soon enter a coupling process that last just moments, and quickly die in a few hours. So why oxidation would begin to work just from this point?
Still more, in the case of insects and other animals, there is no sufficient time in a few hours for oxidation process to take to death. Here is mystery that hardly will find a scientific answer, and this would again force us to doubt of this approach like main cause for aging.
LOOKING FOR A HOLY GRAIL THAT DOESN'T EXIST
When reading the scientific works on this matter, we notice the obsessive looking of researchers by certain genes that controls in some way the oxidation, replication or other processes, considered as cause for the aging. By finding these genes, they will get probably many treasures for us, but it is possible also that scientists are looking for a 'Holy Grail' that does not exist to solve aging. To reach this conclusion we should advance a little more in this reading.
If reproductive epoch plays a so crucial role in the aging process, couldn't be obtained some benefit by extending this epoch to the maximum possible? The idea is quite simple, and it was enunciated at first by the British-Indian scientist 'Sir' Peter Medawar, disclosed in the book 'The Selfish Gene' of Richard Dawkins (see 9) .
The idea is as follows: males and females become separate from the birth, and it is not allowed for them to couple until arriving at a certain age higher than the normal one for this act. Because exists small differences in the abilities and qualities of individuals in any population, some still will have enough forces and vigor to complete the sexual act at an age above than population's average, and this characteristic (good health and vigor) will be transmitted to descendants. By repeating this process again and again, wealthy individuals could be obtained with vigor at ages very superior to the normal ones, letting nature to solve the genetic and engineering problems necessary to maintain a well-care organism at higher ages.
The same process (selection) is applied by men throughout thousands of years to get hens producing more eggs, or cows with greater capacity in milk production, therefore, it wouldn't be a mistery if the process works also when the desired quality is a higher age. This has been the explanation of Charles Darwin for 150 years, known as 'natural selection' (or in this case, artificial selection made by the man).
The idea of Sir Medawar was carried to practice in several experiments made (among others by Michael R. Rose of Irivine Univ. in California - see 1) with fruit flies and other insects, obtaining individuals with a life 2 times greater than normal. These 'super flies' lives perfectly healthly 2 times more than the rest of their brothers.
These experiments show that, although it is possible to slow down aging by using single selective processes, these cannot be applied easily to the humans for obvious reasons. It would be impossible in actual humans realm to establish directives allowing reproduction only for healthy and vigorous individuals of certain age.
Anyway, exists undoubitatly a close cause-effect relation between the reproductive period (maximum vigor) and the beginning of aging. The question is: what is this relation? why nature forgets a sophisticated machine, once carefully preserved, and allows it to decay from the exact moment than this engine generates off-springs? The answer is extraordinarily simple, and as stated at the beginning, it is based on a single phrase: "it is not possible to teach what it is not known". The truth is that nature does not forget anybody, because there is nothing to be forgotten, and this is what we are going to explain now.
IT IS NOT POSSIBLE TO TEACH WHAT IS NOT KNOWN
Perhaps the difficulty to see the obvious is caused by the persistent idea we have about us like being a 'well finished products', like automobiles or TV set, and therefore, condemned to a natural aging. This it is an error, since on the contrary, all our cells are continuously renewing, duplicating themselves, and transmitting information through genetic activators and other proteins throughout the time, until the same moment of our death.
Think about this: a small village grows from nothing, until transforming into a big city. This city is plenty of signboards ,posters, traffic lights and other indicators, which informed in the past, and even now says to it how should continue growing in orderly form, say to it how people must behave, where citizens must walk, where they can find feed and so. It is a wealthy and happy city, where every element of it has precise information all the moment about how acting in the day by day basis.
Suddenly, at certain moment these signboards and traffic lights stop working. They are eliminated of life in the city. People and vehicles begin to move randomly, hitting one against the others in chaotic form, buildings are raised in mistaken places and streets opened anywhere, until life of its inhabitants becomes impossible. At last, people abandons the city, until it finishes depopulated. This is the aging and death, and as we see, it doesn't have anything to do with how old is the city, but only with the lack of necessary information for its correct operation.
Now please pay attention to the following: When multicellular being is generated, genetic activators will guide every one of its cells during development, telling them exactly how they should operate as they are divided, in the same way that those traffic lights and posters did with our city. But then arrives the moment that it must generate off-springs and pass to him all things it knows (genetically speaking) for his future development. At this moment, the organism just knows the way to follow to reach this point (reproductive age). And is exactly this (and only this) information that will communicate to the next generation. It cannot inform its descendants how they should behave after that age, because gender itself doen't know about. Then, from this moment, activators and information proteins will begin to move in randomic way, generating the chaos, just like it happened with our city. The organism begins to age.
THE LABYRINTH OF LIFE
There is another analogy that could help to understand this idea: imagine a dark and dangerous labyrinth like DOOM game. This labyrinth has a single entry point, with a queue of people waiting to enter one at time. Nobody knows if some exit door in the building exists, but nevertheless, there is a small aid for people who enter there. Somewhere at midway into the labyrinth there is a telephone that communicates with the entry point. Whether somebody is able to orient itself and arrive to the telephone, immediately he calls to the entry door and explain the following person how to move into the tunnels, at least to arrive until the telephone. After completing the call and inform the novice, our traveller continues to advance in the labyrinth looking for some exit.
He can't explain the novice what is after the telephone, since it is a way that has not even been walked, and therefore, not known. The labyrinth represents the life, the entry point is the birth, to take the telephone and make a call means to generate a new offspring, and the information to arrive until it (telephone) are those within the genetic code. Nobody knows where will go to finish the trip, or any other information after this point.
The process is repeated continuously with every person entering the labyrinth. All of them are able to arrive at the telephone without problems, so that the previous traveller explained it clearly, but from this point, they begin to journey with no information. From this point all of them begin to 'age', because their genes do not know what to do next, and start behave in erratic form. His ancestor has not informed to him what there is after the telephone in the labyrinth of the life, since ancestor itself does not know it either.
To extend the age by Sir Medawar process, is equivalent to take the telephone a little but inside in the labyrinth. This explanation (for aging) nothing has to do with deterioración because time, by oxidation or blurred back copies, but just because ancestor is not able to inform descendants the following info: how the complex mechanism of genetic activators and other wonderful chemical switches should behave after descendants have been generated?
When watching this process like in accelerated movie, it will appear obvius the statement that 'organism ages because it already completed its duty, which is to generate off-springs'. But that is not true. Nature has no means of knowing what is obvious or not, but it only executes what should be executed. In this case, body decays because their parents weren't able to tell him what to do after some point.
It is like a 4 x 100 stick race, at the moment a runner passes the stick to the following one, he immediatly abandons the race. The genetic information of whole specie is the stick. It runs without pause around the racecourse, while runners disappears one after another. The whole species remains through genetic pool, whereas the individuals disappear. It is evident that, once the genes (and their activators) do not know the next steps to follow, it becomes impossible find a treatment to repair it. Even with body maintained artificially in a gold cage, with no stress, accident or disease, it will age without remedy, the same way that ours once beautiful city will become inhabitable after having erased all its tags.
For those who know little chaos theory, the life and aging of multicellular beings are good example of chaotic system, where starting from determined point, it enters an irremediable spiral of imbalance, and ends up falling down, like a pencil precariously maintained by the tip on a table. The little moment at which the pencil is able to stay on tip (alive), is because genes know the way to maintain the balance, like jugglers balancing hands to alleviate the oscillations. At the moment that this information fails, the pencil unbalances more and more until falling.
The reversion of this process would imply in a complete reprogramming of information contained in the genes. This task seems very difficult, given the complexity in deployment of trillion cells throughout time to form a complete being. If our cells are able to advance in orderly form in the labyrinth of life until certain point, is because that information was stored and compressed gradually throughout hundreds of million years, in a simple trial and error process. Exactly as if the individuals had discovered the path until the telephone, looking randomly during many years within the labyrinth. This trial and error learning by evolutionary paths is very well explained in (10) by the same clever man who created super flies.
To replace this trial and error process by another more efficient appears almost impossible, given the complexity of our bodies. Perhaps it will happen, if genetic engineering continues advancing so fast. Many scientific conquests that in the past seemed as miracle, today became reality, and thus we shouldn't lose hope to overcome aging someday definitively, or maybe the death.
A fundamental requirement for this tale is without a doubt the understanding of phenomenon in its totality.
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Miguel A.V. Mulá (author can be contacted at firstname.lastname@example.org)
1 - Why do we age? - Ricki L. Rusting - Scientific American Dec 1992 Vol 267 Num 6 Pag 86
2 - The Big Bang of Animal Evolution - Jeffrey S. Levinton - Scientific American Nov 1992 Vol 265 Num 5 Pag 52
3 - Why and How Bacteria Communicate - Richard Losick & Dale Kaiser - Scientific American Feb 1997 Vol 276 Num 2 Pag 52
4 - The Artistry of Microorganisms - Eshel-Ben Jacob & Herbert Levine - Scientific American Oct 1998 Vol 279 Num 4 Pag 56
5 - What Controls the Cell Cycle - Andrew W. Murray & Mark W. Kirschner - Scientific American Mar 1991 Vol 264 Num 3 Pag 34
6 - How Gene Activators Work - Mark Ptashne - Scientific American Jan 1989 Vol 260 Num 1 Pag 24
7 - The Hidden Genetic Program of Complex Organisms - John S. Mattick - Scientific American Oct 2004
8 - The Stem Cell - David W. Golde - Scientific American Dec 1991 Vol 265 Num 6 Pag 36
9 - The Selfish Gene - Richard Dawkins - Oxford University Press 1976 (chapter 3)
10 - Can Human Aging Be Postponed? - Michael R. Rose - Scientific American Dec 1999 Vol 281 Num 6 Pag 68
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