Aging and gene expression
Scientists have found out how protein synthesis affects aging
Biologists from Moscow State University together with colleagues from the Harvard School of Medicine studied how protein biosynthesis in mouse organs changes with age. This gives an understanding of one of the fundamental mechanisms of the aging process. The results of the study are published in the journal Proceedings of the National Academy of Sciences (Anisimova et al., Multifaceted deregulation of gene expression and protein synthesis with age).
Aging is based on damage that accumulates over time in the cells, tissues and organs of living organisms. Protein biosynthesis is the most important metabolic process for which the cell spends most of the energy produced. Its disorders contribute greatly to the aging of the body as a whole.
It is known that some effects that reduce the efficiency of protein synthesis increase the life expectancy of animals. For example, in the absence of amino acids – when an animal is starving – or in conditions conducive to protein denaturation – during overheating or intoxication – the level of protein synthesis drops, and this adaptation allows the body to survive in adverse conditions.
The effect of slowing down protein synthesis, prolonging life, occurs in the organisms of some animals with a low–calorie diet or the use of drugs that reduce the activity of one of the main regulators of protein synthesis - protein kinase mTOR.
The authors found out that with age, something similar happens in the liver and kidney of mice: aging cells, as if sensing the accumulation of damage, reduce the level of protein synthesis in order to delay the onset of adverse consequences. The task of scientists was to understand the mechanism of this process.
Scientists from the A.N. Belozersky Research Institute of Physico–Chemical Biology of Moscow State University have been studying the changes that occur with age in various organisms – from yeast to humans - since 2017. The main project of the laboratory was to study the picture of protein biosynthesis in the organs of mice of different ages by ribosomal profiling.
"This ultramodern method appeared relatively recently and made a real revolution, bringing all the advantages of systems biology to the field of protein biosynthesis," Sergey Dmitriev, one of the authors of the study, senior researcher at the Research Institute of MSU and IMB RAS, is quoted in a press release from Moscow State University. – In the cell, protein is synthesized by special molecular machines – ribosomes. They "translate" (translate) gene sequences from the language of nitrogenous bases, on which information in DNA and RNA is recorded, to the language of amino acids, which make up proteins. The ribosomal profiling method allows you to simultaneously determine all the RNAs that are currently being translated by ribosomes in the cell. For this purpose, a new generation of sequencing and complex bioinformatic data processing are used."
Both the biochemical and the "computer" parts of the study were carried out at Moscow State University, taking into account the experience of American colleagues.
Alexandra Anisimova, a graduate of the Faculty of Bioengineering and Bioinformatics of Moscow State University, the first author of the article, says: "Thanks to the unique experience gained in the laboratory of Vadim Gladyshev in Boston, we were able to apply the ribosomal profiling method to two organs – the liver and kidney – of mice of different ages. This made it possible to characterize in detail the changes in gene expression at the level of protein biosynthesis during aging. We found changes in the synthesis of components of many important processes and regulatory pathways, including those related to immunity, inflammation, extracellular matrix and fat metabolism. But the most striking observation that we made concerns a decrease in the rate of development of the components of the protein-synthesizing apparatus themselves – ribosomal proteins and translational factors."
"The results obtained help to understand the fundamental mechanisms underlying the aging processes. At the same time, we are learning a lot about the molecular mechanisms of protein biosynthesis," notes Vadim Gladyshev, one of the leaders of the work, Professor at Harvard School of Medicine.
Currently, scientists are continuing research in order to find out exactly what effects on the body of mice lead to an increase in life expectancy.
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