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Biological ageing

More than to be a real research task, which follows takes up the ideas rather freely that professor Steven Austad exposes in his enthralling book [1], of which I highly advise the reading with any person interested by the subject.

Drosophila	0,1
Mouse	3
Eel	6
Turkey	12,5
Goat	18
Bat vampire	19,5
Cat	21
Canary	24
Mottled salamander	25
Lion	29
Ox	30
Grizzly	31
Small brown bat	32
Dog	34
Pigeon	35
Chimpanzee	37
Sturgeon	50
Alligator	56
Elephant	57
Horse	62
Macaw	64
Man	90
Giant tortoise	177

Noted maximum longevity (in years) of some animal species
(Sources: Encyclopædia Britannica, Quid and [1])

Ageing and longevity

It is initially a question of precisely defining the biological ageing, which one calls also the senescence, and to give reliable indicators of them. Steven NR. Austad [1] gives the following definition of ageing: the progressive deterioration of the near total of the functions of the organization in the course of time.

The first criterion which comes to mind to characterize ageing seems to be the longevity or life expectancy, i.e. the average lifespan of an individual. However, it is clear that this data does not depend only on ageing, but also of environmental criteria. Let us consider, as the Nobel Prize of medicine Peter Medawar did it, the hypothetical example, rich in lesson, of a population of test tubes in a laboratory. If one neglects the cracks which can possibly affect their brittleness, these tubes “do not age” not. However, the environmental pressure represented here by handling of the researchers and laboratory assistants will lead fatally to the breakage of each test tube. One can thus completely speak about the longevity of a test tube, but this one does not have any link with any intrinsic ageing but depends exclusively on the skill of the experimenters. Thus, according to the laboratories, the life expectancy of a test tube can be multiplied by ten. It is the same in the animal populations. Two groups of individuals of the same species, who must thus present a similar biological ageing, will be able to have a very different longevity according to whether it are in nature or in captivity, according to the number of predatory, etc It is necessary for us thus to give up using the simple criterion of longevity to characterize biological ageing.

One could then be tempted to use measurements of sporting prowesses: it is for example clear that an old person cannot compete on one 100 meters with a young man. However, ageing is not the only cause of a possible fall of performances: an athlete starting to smoke and more not to supervise his feeding will see without any doubt his results dropping spectacularly, without that being due to the ageing of its organization. Similar problems occur when one is interested in other functions of the organization, like the memory or the fertility.

In fact, a good indicator of ageing seems to be the evolution of the death rate, which one can identify with the probability of dying in the year which comes, at a given age. Mortality follows to the adulthood an exponential growth: if it passes from 1% to 2% in a given time, it will pass from 2% to 4% in same time. Obviously, the precise rates of mortality of individuals of the same species depend on many factors. A man for example will have a weaker probability of dying if it saw in an industrialized and highly medicalized company that if it lives in a company based on agriculture and strongly sensitive to the epidemics. In the same way, these data are the different ones in times from war or times from peace, or according to whether one is man or woman (the women present in the near total of the countries of the death rates lower than those of the men, for reasons undoubtedly biological and nonsociological, but still badly included/understood). However, the doubling time of the death rate seems to be quasi constant inside a species. At the men, it is about eight years. It can in varies from 7 to 26 years, but if one considers only the men of more than 40 years and that one eliminates deaths nondue to natural reasons, one obtains data which can even less vary.

Thus, the doubling time of the death rate gives us a relevant indicator to measure the speed of ageing and to compare the various animal species: ten days for the drosophilas, three months for the mice of laboratories and eight years for the human beings. Within the same species, inequalities vis-a-vis ageing however seem to appear: for example, there are families whose members often have a great longevity. Although one cannot be sure for it, it could be a question there only of one better resistance, transmitted by genes, with certain diseases, and not the deceleration of ageing. One knows also diseases, like the syndrome of Hutchinson-Gilford or the syndrome of Werner, which seem to accelerate the ageing of the people who are reached by it: fall of hair, greater risk of certain cardiovascular diseases, greater risk of cancer for the syndrome of Werner. However, all the signs of the senescence do not appear: the patients are not particularly touched by the diabetes or the disease of Alzheimer. It would thus not be there of a real accelerated ageing but about the appearance of some spectacular and tragic symptoms.

Why ageing

The number of theories which clash in the field of ageing is impressive: the Russian gerontologist Zhores Medvedev in counted more than 300. However a great number of them are not really interested in the causes, but rather in the mechanics of the senescence. In this direction, they are not, necessarily contradictory and can simply describe several aspects of the same phenomenon.

As regards theory of why ageing, only three serious assumptions clashed and two of them appeared erroneous. That does not want unfortunately to say that the third is the maid, the researchers always missing data on the cause of ageing.

The theory of the good of the species

The evolution of a species, via the natural selection, cannot occur that if there is a renewal of the generations. It is indeed only by the reproduction that new gene combinations appear, providing new characteristics to an individual who can thus be better adapted to his environment in perpetual change. The theory of the good of the species consists in saying that ageing precisely allows this renewal of the generations, the oldest individuals dying to leave room to young people. It is thus for the good of the species, and not for his clean, that an individual ages.

One of the facts which seem to be more in favour of this theory is the case of the species like salmon or the marsupial mouse Antechinus. These animals reproduce only once during their life, and undergo at once after an accelerated ageing which results in quickly their death (only the males in the case of Antechinus). It seems natural to explain that by the theory of the good of the species: ageing is not whereas a natural stage of the life, like the birth or the reproduction, this stage making it possible to accelerate the death of the individual and thus to facilitate the renewal of the generations.

However, this theory raises a major problem: it supposes that the evolution selects the characteristics which are favorable to the group and not to the individual. But that goes against the principles of the biology of the evolution. Let us imagine for example a population in which each female gives rise to two children during his life, a male and a female, and which all the individuals die of natural death. This population is balanced perfectly. The population remaining of constant size, the resources have not suddenly missed and the renewal of the generations is done without problems. Let us suppose now that a transfer occurs and that in a female a gene appears which doubles the longevity and thus the number of children. This gene is obviously bad for the group since if it is spread, the population will follow an exponential growth, which will pose the problem of the lack of resources. However, this gene is good for the individual who saw longer and transmits to more children his genetic inheritance. What the evolution predicted, it is that this new gene is spread, since progressively generations, the share of the individuals carrier of this gene will be increasingly important. The selection is thus done on the level of the individual and not of the group and the theory of the good of the species is cancelled.

The theory of the rate of life

The metabolism creates by-products (in particular free radicals) able to damage the cells and which are undoubtedly one of the important mechanisms of ageing. One can thus think that the speed of the metabolism of an individual - what one can call his rate of life - conditions his ageing. Each cell, of some animal species that it is, would have the same “metabolic capital thus”, that one can see like his power consumption. The cells, and thus the organization, would age thus progressively with the consumption of this capital.

A great number of observations appear to support this theory: the taller one animal is, the more it has cells, and the more it saw old (what, at first approximation means that it ages slowly). Drosophilas that one places in a colder environment (what reduces of as much the internal temperature of these cold-blooded animals) live longer, and one knows that a fall of temperature causes a deceleration of the chemical reactions which are at the base of the metabolism. Lastly, an experiment showed that if one underfed rats or mice of laboratory from 30% to 40% per report/ratio a not limited feeding, but by avoiding malnutrition, these animals lived 20% to older 40%. That can be explained by the theory of the rate of life by a slowed down ageing, for lack of fuels to the metabolism.

The consequence which this theory would have had on the human beings if it had appeared true is enough surprising: it would have had to be concluded from it that to age more slowly, and thus to live longer, it would be necessary to eat very little, but sufficiently, and to avoid any physical, large exercise consuming energy!

However, a certain number of animals seemed to make exception to this theory. The bats, first of all, close relations in the face of a great number of small terrestrial mammals, live much older than the latter (whereas a mouse saw only a few years, a bat can live more than twenty or thirty years, according to its species). This characteristic had first of all was explained by the fact that a certain number of species of bats hibernate, and thus have a metabolism very slowed down for a great period of their life. The explanation cannot however hold, because one realized that other species of bats, having same longevity, did not hibernate. Another counterexample with the theory of the rate of life comes from the birds, which with equal size, have metabolic rates and a body temperature higher than those of the mammals. However, the birds can live at a very advanced age: corbels or parrots of more than 50 years are not rare, and it would even seem that certain parrots exceeded the hundred years. Lastly, it was noted that the underfed rats did not decrease in fact not in the long run their metabolism. The theory of the rate of life, very tempting to the idlers who it can be, is thus not valid.

The evolutionary theory of ageing

The disease of Huntington is a mental genetic disease with late release which leads to the insanity then with dead the individuals reached, and whose study made it possible to the famous Haldane biologist to discover an important point for the study of the causes of ageing. It noted that this disease was abnormally widespread, since it touches a person on 15.000 in the European populations. The natural selection should almost have eliminated it, bringing back it torates as for example the syndrome of Hutchinson-Gilford which touches a person on eight million. In fact, the characteristic of this disease is that at the time when it strikes the carriers of gene concerned, those already had practically all the children whom they would have had if they had not been reached. The disease acting in general only after the child-bearing period, the natural selection cannot act above, which explains the high number of carriers.

For including/understanding the phenomenon well, let us take again the example of the population of test tubes. Let us suppose that each tube gives rise to a baby tubes, each year of its existence. Even if the tubes do not age, they are inevitably broken. For example, the rate of breakage amounts to 50% per annum. A tube then has a chance sixteen to live 4 years and a chance on 1024 to live ten years. Let us suppose finally that a gene appears “commits suicide” which causes the explosion of its carrier at the 4 years age. As a considerable number of tubes will have survived until this age and that they will be able still to procreate, this gene will undoubtedly be eliminated by the natural selection. On the other hand, if the age of the explosion is delayed at 10 years, its influence on the population will be quasi-null and the natural selection will not support nor will disadvantage this gene. It is what occurs for the disease from Huntington, it is also what could occur for ageing: this one had to some extent not been envisaged by the evolution, its consequences appearing only because we live in a on-protected environment.

It is as possible as the mechanisms (negative) associated ageing are the counterpart of positive mechanisms being held earlier in the life. Thus, of the experiments on guinea-pigs showed that the male hormones as the testosterone could be at the origin of cancers at a advanced age. There could thus be a cost with the reproduction. It is besides following a period of unrestrained couplings that the Antenichus male about which we spoke higher, dies brutally.

This evolutionary theory of ageing has a certain number of consequences: in fact the animals undergoing a strong pressure environmental age most quickly. It would be absurd for them to waste energy to counter the mechanisms of the senescence whereas they are likely to die quickly, of the leg of a predator for example. It is thus natural that the large animals age more slowly than the small ones, than the birds and bats, having the asset which is the flight, live longer than the terrestrial mammals. And indeed, one realizes that the birds which are not good robbers, like the poultry, the ostrich or the penguins, have the less large longevities, brought back to their size, which other birds (to compare for example longevities of turkey and pigeon in the table above). Lastly, the salmons die after their reproduction because it was them to better devote their energy to procreation, rather than to hope to survive one year more. The evolutionary theory of the ageing thus seems to explain why Nature did not put defenses against the mechanisms of the senescence.

Mechanisms of ageing

Source: The Tallahassee Democrat

One of the principal known mechanisms of ageing results from the formation, during the metabolism, of oxidants, of which free radicals. The latter are atoms or molecules which have an electron not paired on their external layer and which thus react very strongly with other molecules, to stabilize and form new free radicals. This process of oxidation can damage any part of the cell, as the mitochondries which are the seat of the metabolism or the ADN, sits of genetic information. Transfers can thus be caused, and it is known that in fact such transfers are at the origin of the formation of immortal cells, i.e. a cancer. Vis-a-vis this threat, the organization produces a large quantity of supposed antioxydants to stabilize the free radicals. It is known that the vitamins A, C and E are good antioxydants, but their interest in vivo in the fight against ageing is not proven. The organization also defends itself by repairing the damaged sequences of ADN (that is possible because the strands of ADN come per pair, the sequence of a strand resulting from the sequence of the other). However, if repair does not have time to be done before dédoublemement cell (a mitosis), the transfer becomes irremediable.

Another process brought into play by ageing is the reaction of glycosylation discovered by the French chemist Louis Maillard: the molecules of glucose present in the organization can combine with various proteins, thus modifying their structure. When it is known that the functions of proteins precisely depend more share of time on their structure, one includes/understands the damage which can be caused. It is, would seem it, this mechanism which would be concerned in the disease of Alzheimer. There still, the body envisaged defenses: certain phagocytes seem specialized in the destruction of damaged proteins. It should be noted that the two mechanisms previously quoted act in concert, the free radicals accelerating the glycosylation and the latter being able to generate free radicals.

Conclusion - Outlines

The study of ageing is still a young and promising scientific field. If a great number of assumptions were emitted, one lacks a clear causal theory. As for possible medical applications in the deceleration of ageing, let us not be we yet there. The wonder products which promise spectacular effects in this direction have as much scientific validity than the Fountain of Youth. However, all the hopes are allowed in this sector in full boiling. That it is desirable éthiquement or not, the 150 year old man is certainly not for tomorrow, but perhaps for the day after tomorrow…

Bibliography

1. Austad, Steven NR.; Why we age; New York; John Wiley & Sounds, Inc. ; 1997.
2. “File”; Search; July-August 1999; n°322.

Thank you in Jacques Tréton for his bibliographical consultings and in Edouard Maurel-Segala for his second reading.

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