Release date: 2015-01-28
In the laboratory, heterogeneous symbiosis provides a rare opportunity to test what circulating factors in the blood of an animal do when they enter other animals. Experiments with heterogeneous symbiotic optokines have led to numerous breakthroughs in endocrinology, tumor biology, and immunology, but most of the findings occurred 35 years ago. For some unclear reasons, the technology was gradually buried after the 1970s.
However, in the past few years, a small number of laboratories have begun to restore heterogeneous symbiosis research, especially in the field of aging research. By linking the circulatory system of an aged mouse to a young mouse, scientists have achieved some compelling results. In the heart, brain, muscles, and almost every tissue studied, the blood of young mice seems to bring new life to the aging organs, making older mice stronger, smarter, and even their hair. Become more shiny. Currently, these laboratories have begun to identify the components of young blood that are responsible for these changes. Last September, a clinical trial in California, USA, began for the first time to test the benefits of young blood for elderly patients with Alzheimer's disease.
Symbiotic power
In 1864, physiologist Paul Bert conducted the earliest documented heterogeneous symbiosis test. At that time, he removed the skin of two white ribs and then stitched the two animals together to create a shared circulatory system. Biology completes the rest of the work: as the resected capillaries re-grow the capillaries, natural wound healing connects the circulatory systems of the two animals together. Bert found that the fluid injected into the blood vessels of one mouse easily flowed into the other mouse. This work earned it a prize from the French Academy of Sciences in 1866.
From the initial experiments conducted by Bert, the above process has not changed much. This technique has been used in leeches, frogs and insect experiments but has performed best in rodent experiments. By the middle of the 20th century, scientists have studied a series of phenomena using heterologous symbiotic mice or rats. For example, a team vetoed the idea that caries are caused by sugar in the blood by using a pair of heterogeneous symbiotic rats. Only one of the two rats was fed with glucose every day. But because of the shared circulatory system, their blood sugar levels are similar. However, only rats that actually consumed glucose developed dental caries.
Clive McCay, a biochemist and geriatrician at Cornell University, first applied heterogeneous symbiosis to aging research. In 1956, his team joined 69 pairs of symbiotic rats of almost all ages. These joined rats include a one-and-a-half-month-old pair and a 16-month-old pair, which are equivalent to humans aged 5 and 47, respectively. The researchers wrote in their description of the work: "If two rats can't adapt to each other, one of them will keep eating the other head until the latter dies." In 69 pairs of symbiotic rats, there are 11 pairs died of a mysterious symbiotic disease that may be a tissue rejection reaction.
In McCay's first heterogeneous symbiotic aging trial, the young rat's bones were close to younger companions in weight and density after 9 to 18 months of juxtosis in young and aged rats. In 1972, two scientists from the University of California studied the lifespan of aged and young symbiotic rats. Older rats survived for 4 to 5 months more than the control group, which for the first time showed that the circulation of young blood may affect lifespan.
Although these findings are compelling, heterogeneous symbiosis research is gradually being abandoned. Experts who study the history of the technology speculate that the researchers believe that they have learned everything, or that the threshold for applying for heterogeneous symbiosis research to relevant institutions is too high. Regardless of the cause, the trial was interrupted. Until a stem cell biologist named Irving Weissman reborn the heterogeneous symbiosis.
Tracing the source
In 1955, under the guidance of a small town hospital pathologist in Grand Rapids, Montana, the 16-year-old Weissman learned to join mice together. He remembered adding a fluorescent tracer to the blood of a symbiotic mouse and then observed it flowing back and forth between the two animals. "This is really amazing," Weissman said.
For the next 30 years, he continued to use the natural symbiotic animal Sturgeon squirt to study stem cells and regeneration. In 1999, when Wagers was a postdoctoral fellow at Weissman's lab in Stanford, she proposed the study of the movement and fate of hematopoietic stem cells. Weissman suggested that she use symbiotic mice and use fluorescent markers to track cells in one of the mice. Wagers' experiments quickly produced two discoveries about the characteristics and migration of hematopoietic stem cells. At the same time, she also inspired her friends at Stanford University.
In 2002, Irina Conboy, a postdoctoral fellow at Rando Labs, presented a paper by Wagers at a conference club meeting. At the time, Irina's husband, postdoctoral fellow Michael Conboy from the same lab, was drowsy behind the conference room. When he said that the mice were stitched together, he was awakened. "What we have been discussing for years is that aging seems to be related to all the cells in the body, and all the organizations seem to be rapidly declining together," Michael said. However, they can't come up with a realistic experiment to study what regulates body aging.
"I thought, 'Hey, wait, these organizations are sharing blood.'" Michael said, this can answer questions that they have been questioning for years. At the end of the speech, he rushed to Irina and Rando. However, when Michael had not explained his thoughts, Rando said: "Let's do it together."
They collaborated with Wagers, who was responsible for testing the suture of an aged-young symbiotic mouse and taught Michael the technique. After 5 weeks, the young blood repaired the muscles and liver cells of the aged mice, mainly by triggering the aging stem cells to start dividing again.
The team also found that young blood accelerated the growth of aged mouse brain cells, although the work was not mentioned in a 2005 paper describing their findings. In summary, the results of the study indicate that the blood contains some factors that regulate the aging rhythm of different tissues but are elusive.
In 2008, Irina and Michael, who had worked at the University of California at Berkeley, linked muscle regeneration to the activation of the Notch signaling pathway that promotes cell division or the inactivation of transforming growth factor-beta that blocks cell division. In 2014, they identified an anti-aging factor that circulates in the blood: oxytocin. It is a hormone known for its involvement in childbirth and as a binder, and is approved by the US Food and Drug Administration for use in oxytocin. Whether it is a man or a woman, the level of oxytocin will decline with age. When injected into the body of an aged mouse, the hormone quickly restores muscle activity by activating muscle stem cells.
Wagers has been conducting anti-aging research at Harvard University and established his own laboratory in 2004. She recruited experts who study different organ systems to help them study the anti-aging effects of young blood on various organs. With the help of colleagues, Wagers began screening proteins that are abundant in young blood and not found in aged blood. One of them jumped into their eyes: Growth Differentiation Factor-11 (GDF11). Wagers et al. found that direct input of GDF11 alone is sufficient to increase muscle strength and vitality and reverse DNA damage in muscle stem cells.
Human trials should be cautious
Of course, there are some lingering doubts about whether activating stem cells (usually something that young blood does) will cause excessive cell division over a long period of time. "My suspicion is that long-term treatments that regenerate aged animal cells, whether plasma or drugs, can lead to an increase in cancer." Rando said that even if people understand how to make cells younger, some things should be cautious.
Michael Conboy is worried about another thing: he has seen many symbiotic mice die from comorbid diseases, so testing heterogeneous symbiosis techniques on the human body must be very cautious. "I will be very careful about any tests in which a large amount of blood or plasma is regularly input into an elderly person."
In response, Karoly Nikolich, CEO of California-based startup Alkahest, said he understands these safety considerations, but also emphasizes that millions of blood and plasma inputs have been safely carried out on the human body. A preliminary study by Alkahest is expected to end at the end of this year. The company plans to launch more in-depth research to test the role of young plasma in the treatment of different types of dementia and age-related diseases.
Considering that the hopes of the anti-aging field have been constantly eroded, all warnings about young blood are reasonable. Over the past 20 years, researchers have confirmed the anti-aging nature of many treatments, including calorie restriction, chemicals found in grape skins, resveratrol, telomerase to protect chromosomal integrity, and extended length An immunosuppressive drug that lives in rats - rapamycin and stem cells whose function and quantity decline as humans age.
However, there are only two ways, calorie restriction and rapamycin, which have been shown to actually delay or reverse the effects of aging in many mammalian tissues, but neither has been converted to anti-aging therapies. The former produced conflicting results in primates, while the latter had toxic side effects.
In contrast, young blood seems to reverse the effects of aging, and the known safety considerations for the human body may be small. At the same time, relevant results have been confirmed in heterogeneous symbiotic aging studies conducted in various laboratories to date. However, scientists and ethicists are still concerned that human trials will be conducted outside of approved clinical trials before evidence of safety and efficacy of the therapy emerges. Experts warn that unauthorised stem cell transplantation has become an emerging industry, and that unlimited young blood input will become easier.
Source: Science Network
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