动物实验,异种共生,唤醒衰老组织 z-bo 2020-08-19 544

　　Heterosopia is a 150-year-old surgical technique that connects the vasculature of two living animals. This mimics natural examples of shared blood supply, such as tethered twins or animals that share the same placenta in the womb. In the lab, heterogeneous symbiosis provides a rare opportunity to test the circulating factors in the blood of certain animals when they enter other animals. Experiments with xenocolloids have brought many breakthroughs in endocrinology, tumor biology and immunology, but most of the discoveries were made 35 years ago. For some unclear reasons, the technology has gradually been buried since the 1970s.

　　But in recent years, especially in the field of aging research, some laboratories have begun to revive heterogeneous research. By connecting the circulatory system of old mice, scientists have achieved convincing results. In the heart, brain, muscles and almost all tissues studied, the blood of young mice brought new life to aging organs, making older mice stronger, smarter, healthier, and even dyed their hair. . Yes. It will shine more. Now, these laboratories are beginning to determine the components that cause these young blood changes. In September last year, a clinical trial in California began testing the benefits of young people’s blood for patients with Alzheimer’s for the first time.

　　the power of symbiosis

　　In 1864, physiologist Paul Burt (Paul Burt) conducted the earliest documented experiment of heterogeneity. At that time, he removed the skin from the abdomen of two white mice, and then combined the two animals to form a circulatory system. The rest of the work is done by biology: when the wound grows from the suture intersection, natural wound healing connects the circulatory systems of the two animals. Bart found that the fluid injected into the blood vessels of one mouse easily flows into the body of another mouse. This work received an award from the French Academy of Sciences in 1866. from

　　Since Bart’s first experiment, the above process has not changed much. This technique has been used in hydration, frog and insect experiments, but it works best in rodent experiments. By the middle of the 20th century, scientists had used various mice and rats to study a series of phenomena. For example, the research team used a pair of heterogeneous rats to reject the idea that dental caries is caused by sugar in the blood. In two rats, only one glucose was given per day. However, their blood sugar levels are the same because they share the circulatory system. However, only rats that actually ingested glucose will develop caries. Cornell University biochemist and geriatrician Clive McCay (Clive McCay) pioneered the application of heterogeneity to aging research. In 1956, his team brought together 69 pairs of symbiotic rats of almost all ages. The mating mice consisted of a pair of half-month-old and 16-month-old animals, corresponding to 5-year-old and 47-year-old humans, respectively. The researchers wrote in the study description: "If two mice cannot adapt to each other, one mouse will continue to eat its head until the other mouse dies." Out of 69 pairs of symbiotic rats, 11 pairs died. The mysterious comorbidity may be tissue rejection. In MacKay's first exogenous biological aging test, the body weight and density of old rats were similar to that of young rats at 9 to 18 months after the combination of old and old rats. In 1972, two scientists at the University of California studied the lifespan of young and old symbiotic rats. Older rats survive 4 to 5 months than the control group. This is the first sign that young blood circulation will affect life.

　　These findings are convincing, but heterogeneous research has gradually been abandoned. According to experts studying the history of the technology, researchers either believe they have learned everything or the threshold is too high to apply for symbiosis research to relevant institutions. For any reason, the experiment was terminated. Until the stem cell biologist named Irving Weisman resumed the study of heterogeneity.

　　The root of Trace

　　In 1955, under the guidance of a pathologist at a small town hospital in Grand Rapids, Montana, the 16-year-old Weissman learned how to gather mice together. He recalled adding a fluorescent tracer to the blood of symbiotic mice and observed it spreading between the two animals. Weisman said: "This is amazing."

　　In the next 30 years, he continued to use the natural symbiotic sardine ascidian to study stem cells and regeneration. Wagers was a newly recruited postdoctoral researcher at the Weissman Institute of Stanford University in 1999. In 1999, she proposed to study the dynamics and fate of hematopoietic stem cells. Weissman suggested that she use symbiotic mice and use fluorescent markers to track the cells of a mouse. The Wagers experiment quickly led to two discoveries about the characteristics and migration of hematopoietic stem cells. At the same time, it inspired my friends at Stanford University.

　　In 2002, Irina Conboy, a postdoctoral fellow in the Land Club Laboratory, published Wagers' paper at a Diary Club meeting. At the time, Michael Convoy, the husband of Irina, a postdoctoral researcher in the same laboratory, was sleepy behind the conference room. Speaking of connecting mice together, he woke up. Michael said: "For many years, we have been discussing that aging seems to be related to every cell in the body, and all tissues seem to be rapidly decayed together." But they could not think of realistic experiments to study what can regulate the body's aging.

　　"Hey, wait, I thought these organizations share ancestry," Michael said, which answers the questions they have been asking for years. At the end of the speech, he rushed to Irina and Rand. But before Michael elaborated on his ideas, Lando said, "Let's do it together."

　　Young They are responsible for testing the sutures of middle-aged and young symbiotic mice, and cooperate with Wagers who taught Michael. technology. After 5 weeks, young blood repairs the muscles and liver cells of old mice by triggering aging stem cells to start dividing again.

　　The

　　team also found that young blood accelerated the growth of brain cells in older mice, but this study was not mentioned in the 2005 paper describing the results. All in all, the research results show that blood contains some factors that regulate the aging rhythm of various tissues. Elena and Michael worked at the University of California, Berkeley in 2008. He said that muscle regeneration is either the activation of the Notch signaling pathway that promotes cell division, or the inactivation of transforming growth factor beta that prevents cell division. Associated. In 2014, they identified oxytocin, an anti-aging factor that circulates in the blood. It is a hormone known to be related to childbirth and is used as an adhesive. It is an induction drug approved by the US Food and Drug Administration. Oxytocin levels decrease with age, both in men and women. After the hormone is injected into the old mice, it activates the muscle stem cells, thereby quickly restoring muscle vitality.

　　Wagers are conducting anti-aging research at Harvard University and established their own research institute in 2004. She recruited experts to study various organ systems to help study the anti-aging effects of young blood on various organs. With the help of colleagues, Wagers began to screen for proteins rich in young blood but not rich in old blood. One of them jumped into their sight: Growth Differentiation Factor 11 (GDF11). Wagers et al. found that direct input of GDF11 is sufficient to increase muscle strength and vitality, and can restore DNA damage to muscle stem cells.

　　Be careful when testing humans. "My question is that long-term treatment will regenerate old animal cells, whether it is plasma or drugs, which will lead to an increase in cancer." Rand understands how people make cells young. But he said that some things still need attention.

　　Michael Conboy worries about another thing. He has seen many symbiotic mice die from symbiotic diseases. Therefore, he must be very careful when testing human heterogeneous technology. "I pay close attention to tests that regularly inject large amounts of blood or plasma into the elderly."

　　In this regard, Karolyikolich, CEO of California-based start-up Alkahest, said: He said he understands these safety precautions, but also emphasized that to date, millions of blood transfusions and blood transfusions are safe for the human body. The preliminary research conducted by Alkahest is expected to be completed by the end of this year. The company will conduct more in-depth research to test the role of young plasma in various types of dementia and age-related diseases.