A long life is hidden in gene tumblers
Immortality is the cherished desire of mankind. And from a scientific point of view, it is not a priori impossible. The question rests on the mechanism of aging: do cells degrade by themselves, accumulating "garbage", or is it caused genetically. In the latter case, the "death program" is theoretically disabled. Will nematode worms help to find the "switch"?
Recall that all forms of life retain 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 there is a "regime change" and the production of free radicals in the body increases – for example, reactive oxygen species.
Studies of nematode metabolism have shown that with a decrease in the level of oxidation, the lifespan of worms increases. In some experiments – almost twice as compared to 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, capable of influencing regeneration, was localized in mice – it became more active with age, leading to cell degradation.
The problem is that it is quite 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 is and where the effect is," explains biochemist Brian Kennedy from the University of Washington.
It means that all 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 DNA sites were responsible for the "real" aging.
And now molecular biologists from Stanford, led by Stuart Kim, claim that for the first time they have managed to obtain direct evidence of the existence of genetic "aging programs". A report on this work is published in the journal Cell.
Scientists conducted a complete 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 "toggle switches" 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 a hereditary program? To do this, the researchers subjected the worms to several types of harmful effects – oxidative stress, virus infection and radiation exposure.
Nothing, however, affected the expression of the three key proteins. Based on the results obtained, the scientists concluded that the launch of aging mechanisms is due to genetic causes. "There are appropriate instructions in the genome of worms," Dr. Kim believes.
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 intervened individuals 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: "Transcription factors ELT-3, ELT-5 and ELT-6 can play an important role in the development of a young nematode, but after performing their function, they simply stop working properly - as soon as the reproductive age has come to an end."
However, according to Dr. Kennedy, based on the data obtained, it is impossible to unequivocally exclude the influence of cellular "garbage" and other (different from the identified) genetic mechanisms. The body is a complicated thing.
On the other hand, the findings of the Stanford group are somewhat consistent with the data obtained during another experiment - this time on humans. It was conducted by a group of gerontologists from the Pacific Health Research Institute, led by Bradley Willcox. A report on this work is published in the journal PNAS.
Hawaiian scientists studied the genetic combinations of 213 people over 95 years old and came to the conclusion that a certain mutation of one of the genes (it was called Foxo3a) increases the chances of surviving the age-old milestone by two to three times. "If you inherited this combination, then consider that you have hit the jackpot," explains Dr. Willcox.
Thus, the hypothesis about the hereditary causes of aging seems to be confirmed. And this is encouraging. In the sense that if it is possible to isolate the corresponding genes, 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 synthesized if a comparative analysis of the molecular complexes of an old and a young person is carried out – by analogy with nematodes.