09 March 2022

Dangerous mistakes

The process of protein synthesis is constantly taking place in cells and sometimes, as in any production, marriage happens. A new study in mice has confirmed the hypothesis, first put forward about 60 years ago, that the accumulation of defective proteins accelerates aging. The researchers focused on ribosomes, in which protein assembly lines are located. 


Ribosomes synthesizing proteins on matrix RNA (mRNA). Each ribosome consists of a small subunit and a large subunit. (Illustration: Lukaves / Depositphotos).

Ribosomes receive instructions from the cell nucleus to create a specific protein, and then amino acids are stitched together in the desired sequence – this is the essence of the translation process. But from time to time ribosomes insert the wrong amino acid into the protein. Such errors lead to the creation of defective proteins that can become toxic to the cell.

In 1963, chemist Leslie Orgel suggested that such translation errors contribute to aging. Orgel's hypothesis was that errors accumulate at an increasing rate until the cell dies, but then the researchers did not find sufficient confirmation of this theory of aging. Nevertheless, indirect evidence exists. For example, laboratory mice, which usually live no longer than 2-3 years, show more errors in protein synthesis than naked diggers, who can live up to 30 years. And when researchers genetically modified yeast fungi, fruit flies and nematodes to significantly improve the accuracy of protein assembly in ribosomes, these organisms lived 23% longer.

To test whether errors during protein synthesis contribute to mammalian aging, molecular biologist Eric Bettger from the University of Zurich and his colleagues genetically engineered mice with error-prone ribosomes. One type of error, in which cells synthesize proteins that are too long, was twice as common in modified mice as in control rodents.

When the modified mice were young, they seemed healthy. But by the time they were 9 months old, which is roughly equivalent to 30 human years, they began to look and behave like old mice: the fur began to turn gray and fall out, cataracts developed and the spine twisted. Like the elderly, the mice began to lose fat and muscle tissue. Their physical indicators also decreased. Compared to their counterparts, the modified rodents could not swim as fast and led a less mobile lifestyle.

Along with these deficiencies, molecular signs of faster aging were observed in animals. Their cells suffered more from reactive oxygen species, byproducts of metabolism associated with aging. Their telomeres (the end sections of chromosomes), which shorten with age, also corresponded to those of old mice. In addition, the decrease in the accuracy of protein synthesis significantly reduced the life expectancy of rodents. The modified mice reached 18 months of age about seven times less often than their unmodified peers.

Thus, the study confirmed that errors in protein synthesis are an important factor in aging. If you create a drug that increases the accuracy of translation in ribosomes, you can achieve healthy aging. But before that, researchers need to confirm that translation errors lead to age-related changes in humans as well.

Article D.Shcherbakov et al. Premature aging in mice with error-prone protein synthesis is published in the journal Science Advances.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru .

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