Immortality is the cherished desire of humanity. And from a scientific point of view, it is not a priori unrealizable. The question rests on the aging mechanism: do cells degrade by themselves, accumulating "garbage", or is it genetically determined. In the latter case, the "death program" is theoretically disabled. Will the nematode worms find the switch?
Recall that all life forms maintain a self-healing environment at the molecular level. However, over time, it ceases to be maintained, and damage to cellular structures occurs, called oxidative stress.
For the last half century, scientists have been trying to understand why the "regime change" occurs and the production of reactive oxygen species - free radicals, for example, increases in the body.
Studies of the metabolism of nematodes have shown that when the level of oxidation decreases, the lifespan of the roundworm parasites increases. In some experiments, it is almost twice the "standard".
And with the help of DNA analysis, it was possible to find out that aging is accompanied by some changes at the genetic level. For example, the p16INK4a gene was localized in mice, which is capable of affecting regeneration; it became active with age, leading to cell degradation.
The problem is that it is rather problematic to link metabolic disorders to some specific mechanisms, random or genetically determined. "In such cases, it is very difficult to tell where the cause and where the effect is," explains biochemist Brian Kennedy of the University of Washington.
It means that all of the above negative processes at the molecular level can accompany aging, and not cause it.
In the course of a number of studies, it has already been possible to establish that changes in the expression of certain genes (that is, in their activity) can affect the life of the organism. However, there was no certainty that these particular DNA regions are responsible for "real" aging.
And now molecular biologists at Stanford, led by Stuart Kim, claim that for the first time they have been able to obtain direct evidence for the existence of genetic "aging programs." A report on this work was published in the journal Cell.
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Scientists have performed a full comparative analysis of gene expression in young and old nematodes. About a thousand differences were identified, which, however, were mainly controlled by only three transcription factors - ELT-3, ELT-5 and ELT-6.
These proteins serve as a kind of "tumblers" that trigger the transmission of hereditary information by activating or deactivating individual genes. And the algorithm of their work in old and young worms was significantly different.
But how to check what controls the transcription factors themselves - the accumulation of harmful mutations or the hereditary program? To do this, the researchers exposed the worms to several types of harmful effects - oxidative stress, infection with viruses and radiation exposure.
Nothing, however, affected the expression of the three key proteins. Based on the results obtained, scientists have concluded that the triggering of aging mechanisms is due to genetic factors. “There are instructions in the worm genome,” says Dr. Kim.
To test the "hereditary" hypothesis once again, the Americans neutralized the expression of two factors (ELT-5 and ELT-6) in worms in old age. As a result, the individuals exposed to the intervention lived one and a half times longer than their normal counterparts.
The lead author of the study calls the process of changing the work of genes "developmental drift" and associates it with reproduction: “The transcription factors ELT-3, ELT-5 and ELT-6 may play an important role in the development of a young nematode, but after fulfilling their function they simply stop working as they should - as soon as reproductive age has come to an end."
However, according to Dr. Kennedy, on the basis of the data obtained, it is impossible to unequivocally exclude the influence of cellular "debris" and other (different from the identified) genetic mechanisms. The body is a complex thing.
There are other versions as well. In particular, we have already written about attempts to find "aging genes" in nematodes. Then the scientists came to the conclusion that aging is a genetic program, but it manifests itself precisely in the accumulation of cellular debris.
On the other hand, the findings of the Stanford group are somewhat consistent with data from another experiment - this time in humans. It was conducted by a group of gerontologists from the Pacific Health Research Institute, led by Bradley Willcox. A report on this work was published in the journal PNAS.
Hawaiian scientists examined the genetic combinations of 213 people over 95 years old and came to the conclusion that a certain mutation of one of the genes (called FOXO3A) increases the chances of surviving the century-old milestone two to three times. “If you inherited this combination, then consider that you hit the jackpot,” explains Dr. Willcox.
Thus, the hypothesis about the hereditary basis of aging seems to be confirmed. And this is encouraging. In the sense that if the corresponding genes can be isolated, then it will also be possible to neutralize them.
Professor Kim, for example, is very optimistic. He is sure that the "elixir of youth" can be completely synthesized if a comparative analysis of the molecular complexes of an old and a young person is carried out - by analogy with nematode worms.