Chinese scientists have identified a key gene responsible for aging. The work was colossal. With the help of a special technology, scientists have "cut" and studied more than 20 thousand genes. Perhaps, thanks to gene therapy, it will be possible to increase the natural life expectancy, writes Keji Ribao.
In the course of experiments with animals, scientists have proven that inactivation of the KAT7 gene can slow down the natural aging process. As a result, 81% of mice in which this gene was inactivated were able to live for more than 130 weeks (about 80 years in terms of human age). Among mice that did not receive gene therapy, only 27% were able to survive to 130 weeks.
Throughout their lives, people try to preserve their youth as long as possible, resorting to various means that supposedly prevent aging. Unfortunately, these tools do not solve the main problem. Is it possible in general to stop the aging of the organism with one action?
On January 7, Science Translational Medicine published the results of a six-year study by a team of scientists from the Chinese Academy of Sciences and Peking University. Using a genome editing platform, they were able to identify a key gene responsible for aging. It is the KAT7 gene encoding histone acetyltransferase.
High-precision mapping of the human genome
Back in 2015, a research team from the Animal Research Institute of the Chinese Academy of Sciences led by Liu Guanghui and Qu Jing established collaboration with research teams led by Tang Fulao of Peking University and Zhang Weiqi of the Beijing Institute of Genomics at the Chinese Academy of Sciences. Using CRISPR technology "genetic scissors", scientists have mapped more than 20 thousand genes contained in the human genome one after another. With the help of "genetic scissors", the gene responsible for a certain trait was "cut out" in the cell. Thus, the study of the state of the cell after gene inactivation was carried out. Young cells were left for further analysis, during which it was determined which gene inactivation would lead to an increase in the life span of the cells.
It was a tedious and time-consuming job. Each cell had to be carefully cut, inactivated, and then tested for inactivation of that gene on hundreds of cells. Moreover, scientists examined more than 20 thousand genes contained in the human genome, and each of them required three to six different "scissors". Thus, tens of millions of cells were grown and selected to obtain accurate results.
After processing such a large amount of data, the research team identified more than 100 new genes affecting human cell aging and tested the functions of the first 50 genes. As a result, it was found that inactivation of these genes can slow down the aging of human mesenchymal stem cells.
Inactivation of a key gene can prevent aging
Among 50 genes, KAT7, encoding histone acetyltransferase, had the greatest influence on the aging process.
In the course of experiments with animals, scientists have proven that inactivation of the KAT7 gene can slow down the natural aging process. As a result, 81% of mice in which this gene was inactivated were able to live for more than 130 weeks (about 80 years in terms of human age). Among mice that did not undergo gene therapy, only 27% were able to survive to 130 weeks.
Inactivation of the key gene KAT7 in mice suffering from progeria (early aging syndrome) increased their average lifespan by more than 20%. “The scale of this increase is impressive. In the end, we only affect one of the tens of thousands contained in the entire genome,”said Zhang Weiqi, a researcher at the Beijing Institute of Genomics at the Chinese Academy of Sciences and one of the authors of the article.
In addition, the scientists also confirmed that inhibition and inactivation of the key gene KAT7 slows down the aging of human liver cells, and also reduces the level of expression of pro-inflammatory factors that lead to aging in the body.
How can inactivation of the key gene KAT7 prevent aging?
Qu Jing, a researcher at the Animal Research Institute of the Chinese Academy of Sciences, explained that the protein encoded by the KAT7 gene is an acetyltransferase that can add an “acetyl” group to histones. Histones are proteins intertwined with DNA in the nucleus, which together with DNA form a chromosome together. Scientists have found that KAT7 stimulates gene expression and triggers cell aging by selectively catalyzing the histone acetylation reaction (H3K14). An early study published in the journal Nature showed that inactivation of the key gene KAT7 aids in treating leukemia. Thus, we see that this gene does not just code for acetyltransferase, its effect on the human body is quite large.
A more complete genetic map of aging will gradually be compiled
The current study identified about a hundred new genes responsible for aging, which also confirms the team's early judgment that the already known genes associated with aging are only a small fraction, and there are many more unknown genes. Scientists have uploaded the relevant research results and data into a database (the so-called "genetic map of aging"), which can be used and updated by colleagues and researchers from China and other countries.
“Our original intention was to expand knowledge about aging. Based on the work done, the genetic map of aging will be gradually replenished. " According to Qu Jing, individual aging is accompanied by the continuous accumulation of aging cells in tissues and organs; elimination or rejuvenation of such cells can reduce the risk of developing degenerative tissue diseases and increase the duration of a healthy life. New data indicate that gene therapy based on inactivation of a single gene is likely to increase the natural lifespan of mammals.