Aging and autophagy
Why didn't we evolve to live forever?
Anna Kerman, XX2 century, based on Medical Xpress: Why we did not evolve to live forever: Unveiling the mystery of why we age
Scientists from the Institute of Molecular Biology (Institut für Molekulare Biologie, IMB) in Mainz, Germany, have made a breakthrough in the study of aging. Researchers have found that the genes responsible for the autophagy process ensure good health at a young age and control the aging process in adulthood. However, the study was conducted on worms.
The results are published in the publication Genes & Development. The authors of the work managed to clearly show that aging is a "by-product" of evolution. In addition, the data obtained during the study can be used in the fight against neurodegenerative diseases, in particular, Alzheimer's, Parkinson's and Huntington's diseases. Autophagy plays a significant role in the development of all these diseases.
Scientists have also demonstrated that "turning off" the autophagy process in old worms improves the functioning of the nervous system, and then the body as a whole.
We're all getting old. The question is whether we should age. Scientists from the laboratory of Dr. Holger Richly from the Institute of Molecular Biology tried to answer it.
As Charles Darwin wrote, natural selection leads to the fact that the individuals most adapted to certain environmental conditions survive and pass on their genes to offspring. Moreover, the more significantly a certain trait contributes to reproductive success, the more intensive selection will be based on this trait. Theoretically, this means that individuals whose genes effectively prevent aging would have to reproduce continuously. That is, contrary to the current state of affairs, from an evolutionary point of view, there should be no aging.
This paradox became the subject of active – albeit purely theoretical – discussions in the scientific community back in the 1800s. And only in 1953, when George Williams proposed the hypothesis of antagonistic pleiotropy, a rational explanation of the fact of the appearance of the aging process in the course of evolution appeared. Williams suggested that during natural selection, genes that ensure reproductive success are preserved. At the same time, selection ignores their negative impact on life expectancy, if it occurs after the completion of the reproduction process.
That is, a mutation that shortens the life span of an individual, but helps to leave more descendants, is considered "good" from the point of view of evolution. Over time, such mutations become fixed in DNA, negatively affecting life expectancy and at the same time allowing the spread of "aging genes" in the next generations.
Although this theory has been confirmed mathematically and empirically, there was no direct genetic and molecular evidence of its validity before.
Jonathan Byrne, co-author of the new work, says: "Everything is well described in the evolutionary theory of aging, but there has been no real evidence of what is happening in living nature until today. Evolution "does not notice" the effects of mutations that are associated with aging, since they manifest themselves after an individual has left offspring.
The genes of antagonistic pleiotropy were not discovered earlier, because it is very difficult to work with old animals. We were the first to conduct a large-scale study in this area and discover a surprisingly large number of genes [30] working in the described way."
Previous studies have already found genes that are necessary for development, but at the same time affect aging. However, the new work has identified 30 genes directly involved in the aging process of mature worms. "Since we have studied only 0.05% of the total number of genes of this species, we can assume that there are still a lot of finds ahead," adds Bern.
The proof that aging is supported by evolution was not the only unexpected result of the study. Says co-author Thomas Wilhelm: "The biggest surprise for us were the processes in which these genes are involved. We have discovered a group of genes that control the process of autophagy, which, in turn, accelerates aging." This is truly amazing, because autophagy is a critically important component of the cell's metabolic processes, necessary for life. It is known that with age, the process of autophagy slows down, and in old worms it actually disappears. Researchers have demonstrated that "switching off" the genes that initiate the autophagy process allows animals to live longer than worms whose genome has not been altered. "This may force us to change our understanding of one of the fundamental cellular processes," explains the head of the study, Holger Richli. – Autophagy is almost always considered as a useful process, even in cases when it goes very slowly. But we have demonstrated that slowing down this process leads to very serious negative consequences, and sometimes it is better to abandon it altogether. Autophagy works correctly in young worms, and they need it to reach maturity. However, after the end of the reproductive age, violations of the course of this process lead to the fact that the worms age."
In the final part of the work, Richli and his colleagues were able to correlate life-extending signals with a certain type of cell: neurons. By "turning off" autophagy in the neurons of old worms, scientists were able not only to prolong the life of animals, but also to significantly improve their health.
"Imagine that you have reached the middle of life and started taking a medicine that allows you to stay as healthy and mobile as those who are half your age. This is about what happened with worms," says Wilhelm. – We "turned off" autophagy in only one tissue, and the animal's body as a whole benefited from this. The worms that underwent treatment had neurons in a relatively better condition, and this helped to maintain the health of the muscles and the body as a whole. On average, we managed to extend the life of worms by 50%."
Although the mechanisms underlying the discoveries made are still unknown, the results of the new work can be used in real life. "Many neurological diseases are associated with disorders of autophagy. These are Alzheimer's disease, Parkinson's disease, and Huntington's disease. It is possible that the discovered "autophagy genes" can help to preserve the integrity of the nervous system in patients with such diagnoses," adds Wilhelm. Although the appearance of such methods of treatment in everyday medicine is still far away, the prospects are very rosy: perhaps over time we will be able to prevent the development of neurodegenerative diseases, while simultaneously becoming younger and healthier.
Aging processes are of concern not only to geneticists and molecular biologists. So, in May 2016 The World Health Organization (WHO) has adopted a Global Strategy and Action Plan on Aging and Health. One of the main objectives of the strategy is to improve the collection of statistics, monitoring and research in the field of healthy aging. You can assist WHO in its work by filling out a short questionnaire. Spending just 15 minutes, you can help healthcare organizers, doctors and scientists working in the field of combating aging and related diseases.
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26.09.2017