Release date: 2014-09-23

What is the purpose of our search for Laoquan? Is it to extend human life or to improve the quality of human life? This is a very sensitive ethical issue.

Amy Wagers, a stem cell scientist at Harvard University in the United States, points out that as people get older, their muscles lose their ability to maintain balance and regenerate. She explained: "I am not saying that aging is a disease, but aging is associated with an increase in the prevalence of certain diseases."

Wagers and many collaborators have shown that when the blood of young mice and the blood of young mice are mixed, shocking physiological changes will occur. Many of the declines in function due to aging, such as muscle atrophy, unresponsiveness, and decreased cognitive ability, have eased and even returned to their original levels.

"Rejuvenation"

“Rejuvenation” has always been a key area of ​​biological research. Wagers and collaborators believe that certain substances in the blood must cause such amazing changes. In fact, after unremitting research, she and her colleagues have recently succeeded in isolating a special molecule, Growth Differentiation Factor 11 (GDF11), from the "young" blood. This molecule seems to revitalize the heart, brain blood and skeletal muscles, at least in animals. Wagers told the research team: "GDF11 is a 'not old spring' for the heart, skeletal muscles and brain, and is a beneficial protein that rejuvenates organs."

In 1998, the world's first human embryonic stem (ES) cells were isolated, making research in regenerative medicine possible. Since then, researchers have been trying to find the magical "not old spring." Wagers asked other researchers: "What is the purpose of our search for '不老泉'? Is it to extend human life or to improve the quality of human life? This is a very sensitive ethical issue."

In fact, other teams working on blood regenerative functions have focused on different proteins, influencing factors, and pathways. However, Wagers expects GDF11 to be part of a regenerative drug in the next four years. “The place I most want to agree with is that aging may be a sign of imbalance in the human body, and we may be able to restore balance to the human body. ."

A key question is whether adult stem cells, such as hematopoietic stem cells, can be treated like embryonic stem cell-derived cells. Some prominent research teams say that these bone marrow cells can be transformed into other tissues, such as muscle tissue, myocardial tissue, and brain cells. To test this, Wagers labeled the hematopoietic stem cells of the mouse and transferred a cell to an old mouse so that she could observe the brain cells, myocardial tissue or muscle cells of the old mouse after the cell transplant. No increase. However, Wagers and Stanford stem cell scientist Irving Weissman saw only rare "fusions" between hematopoietic stem cells and muscle stem cells, without any signs of hematopoietic stem cells producing muscle tissue.

This “negative data” was a turning point in Wagers' career, as some of the research involved mice that shared the circulatory system. The Siamese mouse experiment first appeared in the 19th century and now plays a vital role in the field of aging research.

In 1864, the French zoologist Paul Bert described an unusual surgical procedure that connected the circulatory system of two mice into one. Bert cuts the sideways of two animals (such as mice) and then sews them together with the cut skin so that their bodies will touch each other. When the wound heals, the capillaries of one animal infiltrate into the body tissue of the other animal, and the two animals will share the same circulatory system and transport nutrients to each other. It was not until nearly 100 years later that researchers realized this concomitant symbiosis and provided an efficient method for studying aging and regeneration.

In the 1950s, Cornell University researcher Clive McCay and colleagues reported that a blood circulation system was established between a young mouse and an old mouse (this method is called "heterologous" in immunology. Symbiosis"), the latter's bodily functions will have a certain degree of recovery. McCay proved in the 1930s that if the calorie intake is limited, the life of laboratory animals will be extended. But at the time, high-performance molecular identification methods were not available, and Cornell researchers were not able to study the effects of this surprise.

It wasn't until 10 years ago that the situation changed. Stanford University biologist Thomas Rando and postdoctoral Irina Conboy worked with Wagers and Weissman to reproduce Bert's experiment. They studied how the blood of young animals affects the stem cell function of older animals (such as satellite cells) and how to maintain and repair muscle function, which itself will decline in function as the animal ages.

Rando said: "Siamese experiments are not ours, but we have updated our experimental techniques." Wagers et al. published the results in Nature in 2005, confirming that blood does have magical effects: with young mice The muscle stem cells of old mice that share blood regain their vitality and can repopulate and repair muscle tissue.

What needs to be clarified in the next stage is the reason why the blood of young mice contains substances that can trigger the "rejuvenation" effect, or is there a substance that inhibits the "rejuvenation" effect in the blood of old rats? Wagers An extensive research program specifically designed to identify what is the "systemic factor" in young blood.

Scandal

In the summer of 2010, Wagers realized that her article published in Nature earlier in the year might have missed a problem. Shane Mayack, a postdoctoral fellow with Wagers in a laboratory, pointed out that the phenomenon of "not old spring" may also enhance the hematopoietic capacity of hematopoietic stem cells in old mice.

Wagers worried that the study might be really leaky, and she immediately told Harvard Medical School about it. She did not wait for the results of the review, immediately withdrew the paper published in the journal Nature and communicated with the editor of Blood magazine. Wagers said: "The first thing I think of is that I have to modify this paper."

In 2012, a report from the Office of Research Integrity (ORI) stated that Mayack had academic misconduct. ORI believes that Mayack deliberately uses other research project data that is not related to conjoined experiments to provide favorable conclusions for his experiments. In addition, Mayack also cited online data as first-hand data.

Mayack's behavior caused the experimental leader, Wagers, to suffer a double blow in both psychology and career. She said: "We spent so much research funding and valuable time, everyone worked hard in the lab, and spent a lot of time and experience summarizing data to write a thesis. This is really chilling." Some people accused Wagers on the Internet Not strict. But Wagers countered: "How can a person in charge of a lab be able to cover everything? What we can do is try to avoid being deceived, but it can only be recognized if it is deceived."

The Mayack scandal did not affect Wagers' status at Harvard University, which continued to renew her contract in 2012, and her mentor and friend Weissman strongly praised her rigorous scientific attitude in response to emergencies. Weissman said: "She is a credible person, she will take the initiative to take the fault and will not wait until everything comes to the ground."

Hard looking

Even in difficult times, Wagers and colleagues did not stop trying to find "systemic factors" in the blood of young mice. But she herself admits that it is really difficult to find the secret of "not old spring" in the blood.

Wagers and colleagues cited many possibilities: protein, fat, and hormones. She later recalled: “After about a year of hard work, we began to feel pessimistic that it was impossible to find such a factor.” After that, the team of Wagers began to cooperate with biotechnology company SomaLogic, which provided advanced technology to Wagers. Protein acquisition technology. The Wagers team used the technology to identify 13 factors that are high in the blood of young mice and a decrease in blood levels in older mice. These 13 factors are likely to contain the secret of “not old springs”. In the end, they determined from these 13 factors that GDF11 is the secret of “not old spring”.

"We don't know much about GDF11," Wagers said. GDF11 is a variant of transforming growth factor beta, which contains many proteins that affect body functions such as growth, mutation, and immunity. The Wagers team is now working hard to find out how GDF11 is generated and why the amount of this substance will decline with aging. However, her team can use technology to test the recovery of various physical functions of old mice after injection of GDF11.

The test results are exciting. In 2013, Wagers and colleagues reported in Cell magazine that the effect of injecting GDF11 into old mice alone was as effective as injecting blood into young mice directly into old mice, both of which significantly improved myocardial function in mice. Avoid heart failure. In the spring of 2014, the team of Wagers published two consecutive papers in the journal Science. The article pointed out that when the GDF11 content in old mice returned to the same level as GDF11 in young mice, the body function damage associated with aging It is repaired and enhances the strength and endurance of old mice. The report also pointed out that GDF11 can also enhance the blood circulation of the brains of old mice, promote the survival of new neurons, and ultimately improve brain function.

As the research progressed, some researchers warned that Wagers7 could not be rushed. Some people on the Internet called Wagers' research "vampire therapy." Toren Finkel, head of molecular medicine at the National Heart, Lung, and Blood Institute, said: "It's really exciting news that blood can fight aging, but we have to figure out how it works." Other researchers have also pointed out that injection Growth factors may increase the chance of developing cancer.

Wagers is also cautious about research. Despite the gratifying results, she believes that it is not appropriate to inject GDF11 into patients at this stage, because this method bypasses the organism's own rigorous molecular management system and may have unknown side effects.

Source: Chinese Journal of Science

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