Age Editing
A geneticist is developing a means to prolong life by 30-50 years
Anna Polyakova, Rusbase
Spanish geneticist Juan Carlos Ispisua Belmonte, who works at the Salk Institute for Biological Research in San Diego, is conducting a study that in the future can give humanity a universal way of rejuvenation. Ispisua Belmonte expects that gene editing will allow to reverse aging.
So far, experiments are being conducted on artificially aged mice. After special manipulations, laboratory animals that are already close to death become active again. According to the scientist, not only external changes occur, but also internal ones – all organs of mice are also updated. However, the drug used is too strong, so mice die three to four days after the procedure due to cell malfunctions or later due to the appearance of cancerous tumors.
The Ispisua Belmonte method is called epigenetic reprogramming. This is the reset of the so–called epigenetic labels of the organism - chemical switches in the cell that determine which of its genes are active and which are inactive. When these marks are erased, the cell "forgets" whether it was a skin or a bone cell, and returns to a primitive embryonic state.
The scientist believes that epigenetic reprogramming can significantly prolong a person's life. In his opinion, the accumulation of changes in epigenetic labels causes cells to function less efficiently with age and this may be the cause of aging.
Ispisua Belmonte warns that his method will not allow you to live forever, but will delay the onset of death by 30-50 years. The researcher is convinced that a person who will live 130 years has already been born.
Factors of youth
The drug that Ispisua Belmonte gives to mice is based on the discovery of the Japanese scientist Shinya Yamanaka, who received the Nobel Prize for it. Since 2006, Yamanaka has been demonstrating how adding just four proteins to adult human cells can reprogram them so that they begin to look and work the same as in an embryo. These proteins, which are called "Yamanaki factors", erase epigenetic marks in the cell and give it a new life.
However, there is also a danger in this "zeroing". A dummy cell can grow into a healthy cell or into a cell that will never function. It can also become cancerous – that's why mice in the laboratory of Ispisua Belmonte are prone to the formation of tumors. This proves that reprogramming really happens inside their bodies, but the results tend to be fatal.
Ispisua Belmonte believes that this problem can be solved by choosing the right dose of the drug. He has already tried to limit it for one group of mice – they did not have tumors. Instead, the animals became stronger physically, their kidneys, spleen and heart worked better. As a result, they lived 30% longer than other mice born with them.
The Source of Youth
Not all researchers enthusiastically accepted the idea of Ispisua Belmonte. For example, Jan Wiig, head of the department of genetics at the Albert Einstein College of Medicine in New York, says that aging consists of "hundreds of different processes" for which simple solutions are unlikely.
In addition, scientists doubt that epigenetic changes are the cause of aging, and not its sign. If this is just a sign similar to the appearance of wrinkles, then the procedure Ispisua Belmonte, as well as smoothing wrinkles, will have only a cosmetic effect.
Another fundamental claim: the experiments were carried out only on artificially aged mice, so it is not known what the results of using the drug on animals that have aged naturally will be. Vittorio Sebastiano, an associate professor at the Stanford Institute of Stem Cell Biology and Regenerative Medicine, notes that natural aging is much more complicated. According to him, the study by Ispisua Belmonte leaves this important question unanswered for now.
Mass rejuvenation is still a long way off– if it ever becomes possible. However, there are other ways to use this medical technology.
Xin-Kai Liao and Fumiyuki Hatanaka spent four years in Ispisua Belmonte's laboratory adapting CRISPR-Cas9, a well-known DNA editing technique. The original CRISPR eliminates the unwanted gene, and the tool obtained by Liao and Hatanaka does not affect the genetic code itself, but can turn the gene on or off.
Scientists have tested its work on mice with muscular dystrophy, which do not have a gene for muscle maintenance. Liao and Hatanaka started another gene capable of replacing the missing one. The experiment was successful, and the muscles of the experimental animals became much larger, the researchers say. The Ispisua Belmonte laboratory also worked to eliminate the symptoms of diabetes, kidney disease and bone cartilage loss.
Scientists from Duke University plan to use a similar tool to weaken a gene involved in the development of Parkinson's disease.
The first human trials of these methods are likely to take place in the next few years. This technology is being tested by two companies: AgeX and Turn Biotechnologies. AgeX plans to focus on heart tissue, while Turn plans to focus on age–related muscle loss. Another company, GenuCure, intends to use the discovery of Ispisua Belmonte to rejuvenate cartilage.
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