Experiments on nematode worms helped Russian and American molecular biologists and mathematicians to prove that a certain genetic program controls the aging process. It will be possible to interfere with its work with the help of drugs, according to an article published in the journal Scientific Reports.
In recent years, a debate has revived among scientists about what is the process of aging and death of humans and animals. Some biologists and evolutionists believe that this process is not accidental, and that it is controlled by a kind of "death program". So they call a special set of genes that makes the body grow decrepit and die, giving way to a new generation of their own kind.
Other scientists believe that aging is a completely random process of accumulation of mutations and accidental breakdowns in cells, which leads to the accumulation of so-called "aged" cells in the body. They stop participating in the life of the body due to the appearance of mutations in their DNA or reaching the limits of division. Recent experiments have shown that their removal from the body of worms significantly prolonged their life and improved vital functions.
The existence of naked mole rats and other "immortal" animals, as noted by Pyotr Fedichev, founder of Gero and head of a laboratory at MIPT, led his team several years ago to assume that an aging program should still exist, and that it can be stopped using certain drugs or by changing how genes work.
To search for it, they selected six dozen different varieties of nematode worms, some of which lived for an unusually long time, tens of times higher than the norm, and others for a relatively normal period or unusually short. Biologists have tried to uncover the reasons for the development of these differences by comparing how the activity of their genes changed at different stages of life and analyzing their characteristic sets of mutations.
Scientists were initially interested in the answer to one simple question - why mutations in some genes that nematodes acquired even before they hatched into the world significantly prolonged their life, and their blockage with RNA in adulthood did not bring the same effect.
This led Russian geneticists and mathematicians, as well as their colleagues at the Arkansas Medical University in Little Rock (USA), to suspect that such small changes caused large-scale restructuring in the entire aging program, which was difficult or impossible to repeat.
To test these concerns, Fedichev and his colleagues combined the results of their own measurements and the experiments of other scientific groups into a large-scale database reflecting how the work of all nematode genes changed as they age. They analyzed its contents using a machine learning system capable of highlighting even the most subtle similarities.
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She showed that the aging process really resembled a certain program - the activity of genes in all long-lived worms changed in one direction. In other words, she changed in a similar, not random way. Most importantly, the slowdown in how genes changed their behavior directly reflected how long invertebrates were able to survive.
This discovery led Fedichev and his team to speculate that a similar effect could be achieved with drugs without resorting to genetic interventions. They tried to find similar substances using the CMAP database, which contains comprehensive information on how certain drugs and other substances affect different human genes.
She helped them find four previously unknown drugs that would "slow down" the aging program in much the same way as mutations in longevity genes. Testing them on normal worms showed that they all slow down the aging of nematodes to one degree or another. For example, the most powerful drug, common analgin, extended their life by a third.
