Injecting the blood of young animals into the bodies of older animals can rejuvenate the latter. Such experiments are ongoing, and humans may be able to find ways to delay their own aging.
This is one of the strangest experiments in dental history. In the early 1950s, in order to study the causes of tooth decay, a researcher named Benjamin Camlin turned to a reliable partner in scientific experiments-mice. Specifically, small pieces of skin tissue were cut from several pairs of mice, and then these mice were sutured together in pairs at the incision. About a week after this “fit”, their blood vessels began to fuse, and the hearts of the two mice pumped blood to the shared circulatory system. This situation is called “symbiosis”.
In animals that are genetically closely related, symbiosis works best. By allowing these mice to share blood and genes and feed them various foods, Camlin hopes to prove that it is the sugar in the food that causes tooth decay, not some kind of birth defects of the individual.
Others have made even more amazing discoveries using this technology. For example, the bone density of mammals usually decreases with age. However, after 3 years of the above-mentioned research in Camlin, a study by a geriatrician named Clive McKay showed that The “combination” of old white rats and young white rats can increase the bone density of old white rats. The point raised in a 1972 paper is even more surprising: Compared with old mice in similar conditions, old mice that have obtained blood from young mice can live four or five months longer.
Of course, the white mice themselves didn’t like this test process very much. Early papers described the hazards of “commensal diseases”—an animal’s immune system rejects foreign blood when it occurs. The paper also pointed out that before “fitting” these white mice, they must be cautiously allowed to interact with each other to prevent them from biting each other to death.
Michael Cumbery, a biologist and xenogenetic researcher at the University of California, Berkeley, admits that “this kind of technology itself is unappetizing and somewhat barbaric.” Perhaps for this reason, by the late 1970s, such research had almost disappeared. However, this technology is now back in people’s sight, because a series of recent discoveries show that the research results of previous generations of researchers are indeed important. It seems that the blood of young animals can really alleviate, at least partially, the effects of aging. The promise of this technology is enough to give birth to human clinical trials in this area.
Modern research on heterogeneous symbiosis can be traced back to 2005, when Cumbery, his wife Irina, and several other researchers at Stanford University at Stanford University published a paper in the journal Nature describing how the two The “fitting” test between three-month-old mice and 19-26-month-old mice of the same species is roughly equivalent to “fitting” a 20-year-old young man with a 70-year-old man. Five weeks later, the Cumberys and their colleagues intentionally damaged the muscles of the old mice. Generally speaking, the recovery speed of old animals after this type of injury is much lower than that of young animals, but the recovery effect of these old mice is almost as good as that of young mice in the control group. Young blood has a similar effect on liver cells, making the proliferation rate of liver cells in old mice two to three times the original.
Since then, there have been numerous papers showing similar improvements in other tissues in animals. However, there is no research to reproduce the result that “young blood can prolong the lifespan of old mice”, but some research shows that young blood can help repair damaged spinal cord and promote the formation of new neurons in the brain of mice. Can rejuvenate their pancreas. With age, the heart wall of the mouse becomes thicker, but young blood can reverse this process.
This effect will also work in reverse. Old blood hinders the growth of neurons in the young brain and ages young muscles. This phenomenon even seems to be manifested in different species. In April of this year, Tony Weiss-Cray, who also works at Stanford University, said that after being transfused with human infant’s cord blood, the performance of old white mice on memory tests has improved.
Janet Lord, head of the Institute of Inflammation and Aging at the University of Birmingham in the UK, said that there are now enough research results to dispel people’s doubts and make them believe that something extraordinary is happening, but it must be explained exactly what happened. What is not so easy. The theory is that chemical signals in young blood exert some influence on the stem cells of older animals. Stem cells are special cells stored in the body for repair and regeneration of damaged tissues. Just like other parts of the body, stem cells will age with the age of animals, but certain components in the blood of young animals seem to restore the ability of stem cells to proliferate, and promote them to repair the skin as effectively as stem cells from young animals. Damage organization.
No one knows exactly which ingredient is at work, but people are trying to find it. Lord said that there may be more than one, but dozens or hundreds of hormones, signaling proteins and similar substances are working together. Researchers compared the chemical composition of old blood and young blood, looking for the chemical substance with the biggest difference in levels between the two, including oxytocin (this hormone is more well-known for transmitting signals between neurons); There are also two proteins called GDF-11 and TGFbeta-1, both of which are known to affect cell behavior; there is another protein called B2M, which affects the body’s ability to absorb iron from food.
Richard Lee, a cardiologist at Brigham and Women’s Hospital in Boston, Massachusetts, said that even with a target list, it’s still difficult to figure out what happened. Blood is a complicated thing, and the existing tools for analyzing blood are far from perfect. Dr. Li’s own research is a good example. In 2014, his team discovered that GDF-11 may be a “rejuvenation” factor. The following year, a team from Novartis, a large pharmaceutical company, claimed that they were unable to reproduce the findings of Dr. Li’s team. The Novartis team said that the problem is that the detection method adopted by Dr. Li’s team is sensitive to proteins other than GDF-11, which affects the test results. A few months later, Dr. Li’s team denied this, saying that the problem was actually the Novartis team’s test-the team mixed other proteins during the test. The matter is still pending.
In addition to the chemical composition of blood, there are other possible explanations for the “rejuvenation” phenomenon of heterogeneous symbiosis. One is that older animals may also benefit from the purification of blood by young kidneys and livers, which cannot be achieved by blood transfusion alone. A paper published by Kang Boyi and his team in 2016 stated that rapid blood exchange (thus excluding the above possible purification process) has a “rejuvenating” effect, but this effect is not as good as that obtained through full heterogeneity. That wide.
Another view is that maybe cells from young animals play some role, rather than chemicals in the blood. Researchers modified a mouse’s gene so that its cells can glow under ultraviolet light. In this way, when this mouse “fits” with other mice, the researchers can track the whereabouts of these cells. They found that only a few cells of the young mice were transferred to the old mice when they were “fitted” with the old mice. But Irina Cumbery said that this does not completely overturn the above theory, because the number of cells does not necessarily explain its importance. For example, immune system cells can proliferate rapidly when necessary, and they are the kind of cells that may be helpful to older animals.
It seems that the mechanism of heterogeneous symbiosis is still unclear, but this has not stopped some companies from conducting experiments in this area to explore whether young blood will also play a magical role in humans in addition to rodents. It may not be easy to persuade patients to sew together with others to share the circulatory system. Therefore, these trials used donated plasma instead of full-scale heterogeneity.
One of the companies that conducts such trials is located in California, Ambrosia. The company requires subjects to be 35 years old and pay a fee of US$8,000, which has attracted much discussion from the outside world. After payment, the subjects will be fed plasma from donors under the age of 25.
Due to the unusual design of the experiment, the fees charged, and a lot of hype around anti-aging research, the company’s founder Jesse Kamazin has been accused of making more money than scientific research. Kamasin denied this accusation. He said that plasma is a natural product and therefore cannot be patented. If there is no hope to develop profitable new drugs, pharmaceutical companies will not be interested in sponsoring his research. “If I can do this experiment for free, I will do it for free,” he said, “but the reality is that I can’t.” In fact, although Kamazin would not disclose whether or how he plans to make a profit, he believes that, A large amount of plasma has already been collected-both for blood transfusion and for the extraction of important biochemical substances such as clotting factors. It is wise to test whether the plasma has other useful properties. Although Ambrosia is not yet ready to publish its research results, Kamazin said the company’s initial findings are encouraging.
Another company called Alkahest originated from a research project at Stanford University, which has relatively little difficulty in attracting investment. It was originally formed in JLABS, a biotechnology incubator set up by Johnson & Johnson, a large pharmaceutical company, and received US$50 million in investment from Grifols, a Spanish company that produces various plasma products. Alkahest has commissioned a trial in which 18 patients with Alzheimer’s disease will be transfused with the plasma of young blood donors in 4 doses within 4 weeks. The company’s boss, Karoy Nikolic, said the main purpose of the trial is to understand whether the therapy is safe. He said that the result should be quite clear, after all, blood transfusion is a conventional medical treatment. However, the study will also test whether the blood used can reverse some of the consequences of Alzheimer’s disease, which seems to be effective for rats in similar conditions.
Alkahest plans to present its research results at a meeting in November this year. Since the experiment was conducted by researchers at Stanford University rather than the company itself, Nikolic did not know what content would be shown. However, he said that if the therapy proves to be safe and effective, the next step will be to identify and isolate the effective compound. Unlike plasma, this type of compound is patentable, especially if it needs to be artificially synthesized in the future, and it does need to be synthesized. As Nikolic said, even if the trial goes well, the plasma material extracted from the donated blood is not enough to treat the 44 million Alzheimer’s patients worldwide.
Some researchers view such experiments more carefully than Nikolic. Michael Conboy pointed out that there are risks associated with blood transfusions. “Even if the plasma comes from a properly matched donor, immune rejection may occur,” he said. “The worst case is a systemic allergic reaction that may be fatal.” What
Dr. Li worries about is the hype about such tests. It will inevitably be linked to “anti-aging” therapy. “When talking about laboratory research, I never use words such as’anti-aging’ or’rejuvenating’,” he said. “This can mislead people into unrealistic hopes.”
Lord also agrees that it is too early to talk about reversing aging, but he also said that there are reasons for cautious optimism. For example, improving the self-healing ability of aging muscles may not be enough to fight against death forever, but it can fight aging and physical deterioration and the resulting wrestling-this is indeed a problem for the elderly; even if it cannot cure the Alzheimer’s It is also good to reduce the damage caused by silent disease. Lord said that instead of pursuing longevity, it is better to consider how to extend the “health period.” This is not about immortality, but it is still a great thing.