02 September 2011

The End of aging: Why does life start at 90?

Article by Michael R. Rose The end of ageing: Why life begins at 90 is published on August 10 in the journal New Scientist.
Translated by Evgenia Ryabtseva

In 1939, the British statisticians Greenwood and Irwin (M.Greenwood and J.O.Irwin) published an article in the journal Human Biology, which did not cause any resonance in the scientific community. And it wasn't even that 1939 wasn't the best year for scientific publications, but that it contained statistics that would make any biologist or medic's hair stand on end.

The article described a completely unexpected discovery. Greenwood and Irwin studied mortality data for women aged 93 and older. Contrary to their expectations, the mortality rate after 93 years did not increase, as it happens with aging in less old age groups, but abruptly reached a plateau. It turned out that the mortality rate for women at 99 years is no higher than the mortality rate at 93 years.

The researchers honestly wrote that "at first glance it looks like an absurd speculation." Of course, like any other respected biologist of that time, they believed that with age, "the extinction of the organism should undoubtedly continue."

And if we assume that this is not the case? Suddenly, the aging process really stops? And if this happens at a very old age, why don't we try to stop it earlier, when we are still in "good health"?

The assumption that the aging process stops is contrary to common sense. The fact of aging of the body has been known to biologists and doctors since time immemorial. Aristotle wrote a good book on this subject more than 2,300 years ago. Like biologists of subsequent generations, he considered aging a merciless process of extinction, ending only when death frees a person from suffering. The existing molecular and cellular theories of aging are still based on the assumption that aging is a physiological process consisting in the accumulation of damage, errors of their restoration or elements of disharmony. The theories differ from each other only by the type of accumulated damage. Previously, evolutionary biologists, like the author Michael R. Rose, who study aging, were of the opinion that the purpose of their work was to find out how natural selection allowed the possibility of damage accumulation in the body.

However, things began to change rapidly in 1992, when Jim Carey from the University of California at Davis and Jim Curtsinger from the University of Minnesota independently published landmark articles in the journal Science:
Carey et al., Slowing of mortality rates at older ages in large medfly cohorts and Curtsinger et al., Demography of genotypes: failure of the limited life-span paradigm in Drosophila melanogaster

One of the main problems of the 1939 study was that Greenwood and Irwin analyzed data on people, and a person is a very bad experimental model, since he does not want to live in a laboratory cell, and even lives for a very long time. Moreover, people, whenever possible, try to spend the last years of their lives in relatively comfortable conditions. Therefore, it can be assumed that the reduction in mortality is only the effect of good care.

Carey and Kertsinger studied not a person, but a favorite model of biologists, the fruit fly drosophila, or rather, hundreds of thousands of insects. They kept groups consisting of thousands of fruit flies of the same age in well-controlled conditions and carefully recorded the death of each insect before the death of the entire group.

At first glance, it seems incredible, but the pattern they identified exactly coincided with the data obtained by Greenwood and Irwin: at first, as the population ages, the mortality rate increases exponentially, but after some time (several weeks in the case of fruit flies) this growth stops. Some of the results obtained by Carey are truly incredible: for several months, the insect mortality rate remained at the same level or even decreased. It looked as if a relatively short period of aging was replaced by a long plateau, at which the aging process seemed to be suspended. This time both articles were noticed.

Very soon other biologists rushed in search of "life after old age" and, to everyone's surprise, it was found in all laboratory experiments conducted on sufficiently large populations of roundworms, fruit flies and other insects. However, relatively few large-scale studies have been carried out and no one has tried to repeat such experiments on mice or other mammals. However, the data obtained undoubtedly indicated that the open pattern had previously simply remained unnoticed, since it never occurred to anyone to use large populations to study the mortality rate in old age. The transition to a new level of experimentation confirmed the existence of the "third phase" of life identified by Greenwood and Irwin, which occurs after adulthood and is characterized by a stable mortality rate. However, this was still contrary to common sense.

It was extremely difficult for evolutionary biologists of that time to understand and accept the new data. The generally accepted theory of aging at that time was based on the work of the outstanding evolutionist-theorist William Hamilton. Hamilton believed that in the early stages of the formation of life, any gene that somehow contributes to the death of an organism before it reaches reproductive age was ruthlessly eliminated by natural selection, since its carrier simply could not have offspring. It is logical to assume that the genes that cause death at later stages of life are subject to less stringent selection and can be preserved in the population. According to these arguments, the aging process was formed as a result of the "weakening of the pressure of natural selection" as individuals age.

The fact that inexorable aging is inevitable was a generally accepted axiom, according to which when an individual reaches an age at which "bad" genes no longer affect the success of reproduction, the protective function of natural selection and, accordingly, the survival rate come to naught. The data according to which, in reality, the aging process stops, it was absolutely impossible to reconcile with this theory.

After two years of exhausting thinking about this problem, the author of the article you are reading now, Michael Rose, had the idea that the traditional interpretation of Hamilton's theory was wrong. What if aging is really the result of the weakening of the pressure of natural selection? If this is the case, then the complete disappearance of this pressure may well lead to a halt in the aging process. For help in obtaining confirmation of this assumption, he turned to fellow evolutionist Laurence D. Mueller, who had computer modeling skills.

Together with him, Rose analyzed several computer models constructed taking into account a new interpretation of Hamilton's theory. In each of the analyzed cases, the aging process stopped. It all looked as if the evolutionary theory implying an endless aging process was fundamentally wrong. The results of the study were published in December 1996 in the Proceedings of the National Academy of Sciences in the article Laurence D. Mueller and Michael R. Rose Evolutionary theory predicts late-life mortality-plateaus

Further development of this idea led to even more unexpected conclusions. It turned out that the earlier a population loses its ability to reproduce, the earlier the aging process of its individuals stops. To obtain experimental confirmation of the results of computer modeling, Rose analyzed data collected by hundreds of students who passed through his laboratory on the mortality and duration of reproductive age of several dozen different populations of fruit flies observed over hundreds of generations. No one has ever conducted such large-scale experiments before.

The results were more than impressive. As predicted by the computer model, the earlier fruit flies lost their ability to reproduce, the earlier their aging process stopped and, accordingly, the longer their life expectancy was. The opposite pattern also took place. The results are presented in the article by Michael R. Rose et al. Evolution of late-life mortality in drosophila melanogaster, published in October 2002 by Evolution magazine.

The results obtained were very inspiring, but they did not exclude the validity of another interpretation proposed by Greenwood and Irwin in 1939. It is quite possible that stopping the aging process is an illusion caused by individual differences in the degree of "survivability" of the organism. That is, in each population of flies there are always several "Supermen" and several "Woody Allen", and all the others are intermediate variants. The weak die earlier, and only the hardiest survive to a very old age, which creates the illusion of an abrupt cessation of the aging process.

Biologists still cannot obtain convincing evidence for this hypothesis, and the only model with significant experimental confirmation is the Rose and Muller model described above.

The genetic reasons for stopping the aging process are still unclear. One possible explanation is the so-called "antagonistic pleiotropy" effect, due to the existence of genes that promote survival in the early stages of life, but have a detrimental effect on the health of an aging organism. The results of experiments on fruit flies obtained to date indicate the reality of the described effect, but there is no definitive evidence yet.

Now we already understand that aging is not at all the result of a progressive accumulation of chemical damage, similar to the process of wear of a metal unit. It is a reflection of the model formed by evolution of the decrease in the functionality of the body. As it turned out, Aristotle was wrong, as well as modern biologists trying to explain aging exclusively in the context of cell biology.

All the results of long-term painstaking research obtained by Rose are described in the book "Does Aging Stop?" (Does Aging Stop?). However, according to Rose himself, what is happening now is only the beginning of a revolution in understanding aging and approaches to slowing it down.

About 10 years ago, Rose suggested that stopping the aging process early would be much more effective than slowing its progression. This would increase not only the actual life expectancy, but also the "duration of a healthy life." If aging could be stopped in middle age, it would make it possible to indefinitely prolong the period of life that gives pleasure to a person and save him from a period of decrepitude. In his book and on the 55theses website, Rose and his associates suggest one of the possible methods of implementing this idea.

The assumption is taken as a starting point that as the body ages, the pressure of natural selection weakens. This means that in youth the body adapts more easily to environmental conditions than in old age. Or, in other words, aging is a progressive decrease in the ability to adapt.

However, this is not the only factor. Adaptation takes time, especially if it occurs in response to environmental changes. Therefore, such changes with age can further reduce the ability to adapt and, accordingly, negatively affect the state of health. Only relatively recently it became clear that our species has undergone a very strong change in habitat conditions caused by the environment – the transition from hunting and gathering to agriculture and, accordingly, to a diet with a large proportion of dairy products and carbohydrates. It is quite possible that this was the reason for the shift of "life after old age" to such an advanced age.

Given the weakening of the pressure of natural selection, it can be assumed that a person is well adapted to an agricultural diet in the early stages of life and much worse in old age. This further exacerbates the decline in our ability to adapt associated with aging. And, finally, the transition to agriculture could contribute to an increase in the reproductive age of a person, which, as experiments on fruit flies have shown, is accompanied by a simultaneous shift in the end of the aging process to a later age.

In order to learn how to improve the quality of life in old age and stop aging earlier, we need to pay more attention to our evolutionary history. This task is very difficult, but there are certain hints.

The simplest evolutionary history is characteristic of individuals whose ancestors never lived in agricultural or industrial regions. These populations are very small, but the study of the aging patterns of their representatives is extremely important for assessing the opportunities presented to each of us. The aborigines of Papua New Guinea, whose ancestors got acquainted with agriculture only in the last century, did not have enough time to adapt to it. In the 2009 book "Nutrition and Western Diseases" (Food and Western Disease), Staffan Lindeberg from Lund University, Sweden describes the health benefits that these people can derive from returning to the diet of their ancestors who hunted and gathered food. The calculations presented in the book "Does Aging Stop?" also confirm the idea that the return of people whose ancestors were hunters and gatherers to the lifestyle and nutrition of past generations should shift the deadline for stopping the aging process to a much earlier age.

However, everyone else is in a much more difficult situation, since over the past 10,000 years, people, for the most part, have more or less adapted to the agricultural diet. However, given that the pressure of natural selection is strongest at a young age, it can be assumed that the maximum adaptability to such nutritional conditions falls on the period up to about 30 years of age. At a more mature age, a person has experienced fewer generations of natural selection, which was not strong enough to adapt to a new way of life. Therefore, it is quite possible that the transition to the activity level and diet of hunter-gatherers can be very beneficial for the health of an aging person.

Rose himself has been practically not eating milk and any of its derivatives, as well as cereals, rice and other products of "herbaceous" origin for two years and claims to be very pleased with the results.

He does not suggest that everyone immediately switch to the "stone Age" diet, but recommends that people whose age is approaching the concept of "advanced" think about it. Of course, the expected effect for most of us cannot be compared with the benefits that switching to an ancestral diet can bring to people who do not have an agricultural heritage. However, it may well improve the quality of life in old age.

The existence of an age at which the human aging process stops is no longer in doubt, as well as its potential variability leaves no doubt. And the discovery of the existence of such an age indicates that the desire to significantly increase life expectancy, which has been exciting the human imagination for centuries, is a very real possibility.

Appendix: photo gallery "Secrets of longevity: life begins after 100".

Portal "Eternal youth" http://vechnayamolodost.ru02.09.2011

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