– Humanity is trying to find approaches to prolong life and slow down aging throughout life. Is it programmed into the human body?
Indeed, there was such a hypothesis. There is an inherited genetic disease such as progeria or premature aging syndrome. It is classified into juvenile progeria (Hutchinson’s (Hutchinson’s)-Gilford syndrome) and adult progeria (Werner’s syndrome).
Before the genetic control of progeria was known, some scientists speculated that there was some type of aging program that people with the disease kicked into too early. It was assumed that because such a program existed, it could be canceled, that is, the lifespan of healthy people would be extended. However, this turned out to be wrong.
– From where?
– It turns out that the cause of childhood progeria is mutations in the LMNA gene, which encodes nuclear laminoproteins A and C. These are proteins that form the structure of the nuclear membrane in the cell. The nuclear envelope plays an important role in maintaining the integrity of the cell nucleus and regulating gene expression (activity). Mutations in the LMNA gene lead to the synthesis of abnormal proteins that disrupt the structure of the nuclear envelope and the functioning of the cell.
This can include loss of skin elasticity, reduction in body size, hair loss, changes in bone tissue, etc. leads to a series of changes specific to aging, such as
– Does this prove that there is no aging program?
– I think so too.
I personally am a supporter of the mutational theory of aging. Mutations damage the genes of the repair mechanism, making it less effective. The frequency of somatic mutations increases with age and mutations accumulate. This process is more or less random. And then how lucky: depending on where the mutation occurred.
– It would seem that these mutations are less common in centenarians?
— No, not less. But purely by chance, they didn’t get into important parts of their genes. There is an interesting example of the genome sequencing of many individual cells in various tissues of Hendrikje van Andel-Schipper (Hendrikje van Andel-Schipper, 1890-2005), who was the world’s oldest woman at the time of her death. . She died at the age of 115, she.
Before his death, he agreed to the use of his body for scientific research and the public use of personal data obtained from those studies. Genome data included. He did not suffer from chronic diseases until his death and soon died of gastric cancer metastases. His cardiovascular system was relatively healthy. He did not suffer from dementia.
450 mutations were found in white blood cells, but none were fatal. Telomeres (end segments of chromosomes; a person’s biological age is believed to be determined by the length of their telomeres) were also much shorter than normal.
– Like this? After all, they say centenarians must have long telomeres, right?
“As for Andel-Schipper, his telomeres and hematopoietic tissues have completely depleted their life reserves. We can say that he died of old age.
– What about cancer?
“It certainly hastened her death, but not by much. She was diagnosed with breast cancer at the age of 100 (stomach cancer came on later, shortly before her death), but she was successfully operated on. She was actually lucky because she didn’t have a major mutation in her lifetime. And so Up to 100 years! And then another 15 years the mutations continued, but with the usual frequency.
– It turns out that the maximum time we can count on is 115 years, if scientists learn how to fix mutations.
i think 120
And here we come to the question of gene editing and gene therapy for aging – an area of research that seeks to develop methods to slow or reverse the aging process through gene manipulation.
Is this field of science currently actively developing?
“While there are promising developments for the treatment of certain diseases, there are no approved gene therapies yet for the treatment of aging.
There are two main approaches here – gene regulation and its effect on the expression (activity) of genes. Both approaches are at an early stage of development.
– But is there already research in which, for example, it is possible to increase the life expectancy of mice?
– To eat. For example, relatively recent scientific papers have shown that increasing the expression of genes encoding telomerase can prolong the lifespan of mice and prolong the lifespan of cells in culture.
Other research focuses on genes that control mechanisms related to metabolism and the immune system. For example, research has shown that manipulation of the FOXO3 gene can extend lifespan in humans and animals.
One of the most famous studies was conducted by a group of researchers from the University of Southern California led by Valter Longo. They found that people with the FOXO3 gene variant, which is associated with longevity, have a lower risk of developing a number of age-related diseases such as cancer, diabetes, and Alzheimer’s.
Another study by a research team at Harvard Medical School showed that manipulating the FOXO3 gene can increase lifespan in nematodes and flies.
– Can this be considered a success?
– Not yet. These studies are preliminary and may require additional studies to confirm results and identify possible clinical applications. So gene therapy for aging is still to come.
In addition, the use of gene therapy in the treatment of aging may face many challenges, including the development of undesirable effects and ethical issues.
– If humanity has the “key to longevity”, is it really possible that it is not allowed to be used because of possible inequality?
“That’s not the point. Everyone knows the scandalous story of He Jiankui, a Chinese biologist who edited the gene for two twin girls.
At the end of 2018, He Jiankui announced the birth of twin girls, where he edited the CCR5 gene (introducing the CCR5Δ32 mutation) using CRISPR/Cas9 technology at the early embryonic development stage to make them resistant to HIV infection. .
The CCR5 gene plays a role in the immune system and is involved in protecting the body from infections, including HIV. However, mutations in the CCR5 gene can increase the risk of developing other diseases, such as viral hepatitis and dangerous, fast-growing forms of cancer.
– So the twins will not have AIDS, but maybe they will get more serious diseases?
Yes, this possibility is not excluded. For this, clinical trials are being conducted, which is not in this case. Therefore, most representatives of the scientific community condemned these experiments.
Second, the scientists found them sloppy – judging by the materials he presented in his Hong Kong report,
The genomes of the first two girls did not have exactly the intended changes, and also not all the cells in their bodies were edited.
But they don’t have AIDS, do they?
— I did not see this information. In addition, the presence of an altered CCR5 gene does not guarantee complete protection against HIV.
Despite the fact that the intervention was carried out with the consent of the parents (HIV carriers), He Jiankui paid a large fine and served time in prison.
“It is clear that editing the genome in an embryo is a risky idea. But is it possible to edit its activities?
– Yes, this is a different approach – regulation of gene expression with the help of interfering RNA.
RNAi therapy is currently used, albeit with varying success, for the treatment of both some hereditary diseases (amyotrophic lateral sclerosis, hemophilia, Down syndrome, and others) and infectious diseases.
Now RNAi therapy is also under research and development. However, it is interesting to note that there is a growing number of studies showing that RNA can enter human cells with food through the digestive tract and affect us through the regulation of the activity of our genes.
– So, does food affect the activity of our genes?
– Definitely. Now the Chinese are working hard on medicinal plants. Previously, it was not clear why the medicinal effect was observed, what it consisted of. And now, in some cases, the short RNA of these plants has been shown to affect the expression of human genes associated with a particular pathology and thus have a therapeutic effect. If so, they can eventually be synthesized and taken as medicine.
Understanding this mechanism, the Chinese are now officially registering traditional Chinese medicine drugs that were previously considered questionable due to the lack of disclosure of their mechanism of action. Among these drugs may be those that increase the activity of genes associated with repair mechanisms. In this way, truly working, revolutionary geroprotectors can be created.
Is it possible to completely reverse aging?
Hypothetically, yes. But so far this is far from it.