Healing with young blood

Vampires, lamias, akshars, ghouls... It is difficult to find a civilization where, since ancient times, there have been no stories about creatures drinking human blood. Even in the modern world, there are rumors that North Korean dictator Kim Jong Il injected himself with the blood of young virgins to slow down aging. (According to other sources, this was done by his father, Kim Il Sung, and his blood was transfused from young men – VM.)

Scientists have adopted these Gothic stories, and have been using them in their experiments with parabiosis for more than a century and a half.

Parabiosis (from Greek para – about and bios – life) is a surgical technique for studying the role of blood factors in the activity of the body. The circulatory systems of the two mice are surgically connected and form a common blood circulation. So the body of one rodent receives molecules from the blood of the second. If the connected mice are of the same age, then parabiosis is called isochronous, and if different – heterochronous. When studying young and old mice on parabiosis, scientists discovered some blood factors that affect stem cells (for example, Irina Konboy's 2005 study), and elements of the endocrine system.

Since the animals used are genetically very close, tissue rejection does not occur. A pair of mice or rats can live in such a symbiosis for several months or even years.

Siamese twins are considered a natural example of parabiosis.

History of the method

For the first time, the connection of two circulatory systems was used by the French physiologist Paul Bert in the 1860s in experiments on rats. In 1908, German surgeons Ferdinand Sauerbruch and M. Heyde introduced the term "parabiosis". By the middle of the century, parabiosis had become one of the main tools for the study of the endocrine system, according to the 1952 Finnerty review.

In the 1950s, Clive McCay of Cornell University in Ithaca, New York, showed that the cartilage of old mice was rejuvenated by heterochronous parabiosis.

Ludwig and Elashoff even showed in 1972 that an old organism can live longer on heterochronous parabiosis than on isochronous, i.e., receiving blood from an animal of the same advanced age.

The peak of publications occurred between 1960 and 1980. More than 1,700 articles related to this technique have already been published around the world. After a long break, it seems that interest in parabiosis is reviving.

Modern research

Despite the long history of the use of parabiosis, the mechanisms determining its result were largely unclear. A new round of discoveries began in 2005 at Stanford University in California – with the work of Thomas Rando and his colleagues, including the aforementioned Irina Konboy. The researchers found that in the heterochronous technique, "young blood" brought the liver and bone stem cells of old mice to a younger state. In addition, the damaged muscles were restored in the same way as in young animals.

More recently, Benjamin Alman, professor of surgery at the Hospital for Sick Children in Toronto and his colleagues showed that the broken bones of old mice healed faster and better on heterochronous parabiosis compared to isochronous.

Scientists explained this by the fact that the level of beta-catenin, which increases in old age, is reduced by factors from young blood. In young rodents, on the contrary, regenerative abilities have somewhat deteriorated.

The research wasn't just about bones. In 2012, Amy Wagers from Harvard studied age-related cardiac hypertrophy: with age, the heart muscle increases. After 4 weeks with connected circulatory systems, the heart of an elderly mouse shrank to the size of its young "partner", and the size of the heart of a young mouse seems to have remained unchanged.

The following year, Loffredo and colleagues, also studying age-related hypertrophy of the heart, linked the improvements from the introduction of young blood with the loss of factors of "youth" with age, and not the accumulation of certain molecules to old age

Infographic: Elsevier Inc.

"Fountain of Youth"

In studies on the heart muscle, scientists have discovered a magic factor whose concentration decreases during aging. This is GDF11, a blood-circulating member of the TGF-beta protein family.

To test, the researchers injected GDF11 into old mice daily – after 30 days, their hearts shrank about as much as in heterochronous parabiosis. (The reliability of the data obtained is still in question – VM.)

In addition, it was later shown that daily injections of GDF11 increase the number of blood vessels and stem cells in the brain. Harvard stem cell specialist Professor Lee Rubin comments: "We believe that, at least in general, it will be possible to reverse some aspects of aging with a single protein."

Scientists have also managed to identify blood factors whose plasma concentration increases in mice and humans with age. One of these molecules is the chemokine CCL11, eotaxin, whose systemic administration disrupts neurogenesis in young mice.

CNS

Experiments using the blood of young animals have shown excellent results for the central nervous system – and, perhaps, this is one of the most promising discoveries. The laboratory under the leadership of Robin J.M. Franklin studied the processes of remyelination – the restoration of the myelin plates of neural processes that are formed by oligodendrocytes and serve as isolation during signal conduction. In an animal model, scientists caused the demyelination of the spinal cord by injection of a toxin. It turned out that during heterochronous parabiosis, angiogenesis at the site of the lesion increases and the level of the oligodendrocytes themselves and their progenitor cells is restored. In addition, young macrophages are also involved in remyelination.

The group of Tony Wyss-Coray from Stanford, who injected blood plasma from young animals to old mice, in 2014 showed an improvement not only in physical endurance, but also in cognitive functions and synaptic plasticity.

Interestingly, the factors of "youth" selectively caused molecular changes in the regions of the central nervous system sensitive to aging. "We have restarted the aging clock," says Viss-Korey.

Finally, five weeks of heterochronous parabiosis caused the formation of new brain vessels, enhanced neurogenesis and the ability to distinguish odors in the work of Lee L. Rubin.

These studies show what therapeutic potential "rejuvenating" factors could provide for the restoration of the central nervous system.

Critical view

After so much work on animals, several reasonable questions arise. Firstly, if so many individual parameters of the state of health are improved by the influence of "factors of youth", will such therapy lengthen life? So far, a 2014 study by Russian scientists gives a negative answer. Two plasma injections per week (one intraperitoneally, the second intravenously) to 10-12-month-old mice from 2-4-month-old for 16 months did not significantly affect the median or maximum life expectancy.

Irina Konboy, who works with Rando, said in an interview that she does not want to speculate on the topic of immortality or the "fountain of youth", but she suggests that "factors of youth" can delay the onset of age-related degenerative diseases and prolong the productive period of a person's life.

The second question is: is it possible to project the results of experiments on animals to humans? Will the results be equally successful? Dr. Eric Karran from the charity Alzheimer's Research UK believes that despite the fact that improved memory and learning abilities have been shown in mice, the significance of studies with "young blood" for humans is unknown.

The researcher Viss-Korey is looking for an answer using practical methods: his preliminary developments show that human blood rejuvenates old mice in the same way as young mouse blood. "We saw amazing effects," the scientist comments.

A bright future

Today, the scientific world cannot offer safe and well-working anti-aging techniques. However, the social demand for rejuvenation is huge. For example, after the Rando group published the results, the phone of the head of the laboratory rang without a break: they even asked about muscle building from the editorial offices of men's magazines and whether parabiosis would help to avoid death.

In California, they want to test the success of animal experiments on patients with Alzheimer's disease by blood transfusion of people younger than 30 years old. Viss-Korey and colleagues are doing this: in the fall of 2014, they were going to evaluate the cognitive functions of each patient immediately before and within a few days after transfusion, and then monitor each participant for several months.

Portal "Eternal youth" http://vechnayamolodost.ru

08.07.2015