Saline instead of young blood?
The healing effect of young blood was attributed to the dilution of old
Polina Loseva, N+1
American gerontologists have found out that dilution of blood plasma with saline solution in itself has a strengthening effect on the liver, muscle and brain tissues of mice. A similar effect on the cells was also exerted by the blood serum of people who underwent plasmapheresis – therapeutic blood filtration. This means that risky and ethically questionable blood transfusion from young donors may give way to filtration of a person's own blood, although its rejuvenating effect has yet to be proven. The work was published in the journal Aging (Mehdipour et al., Rejuvenation of three germ layers tissues by exchanging old blood plasma with saline-albumin).
The idea that the blood of young organisms can facilitate the health of old ones is still considered controversial by many scientists. In the second half of the twentieth century, many experiments were conducted with mice of different ages, in which animals were sewn together in pairs with sides (this design is called parabiosis). In several cases, when one of the animals was old or sick, and the second was young and healthy (heterochronic parabiosis), the health of the old individual became better. Parabiosis helped with radiation and muscular dystrophy, and in some experiments even prolonged the life of old individuals.
However, it turned out to be more difficult to find out what exactly provides this effect. Perhaps it's just that the organs of a young individual work for two. It is quite simple to check this: you need to stop stitching individuals and start transfusing blood between them. In such experiments, sometimes it really turned out to achieve positive results – to such an extent that transfusion is now being tried as a remedy for Alzheimer's disease.
Another possible explanation is that young blood contains some substances that act on the tissues and organs of an old animal. But since blood consists of hundreds of substances, the search for one specific one is not an easy task, which has not yet been solved.
Finally, the third answer is that the effect of parabiosis is not associated with the young, but with old blood. It contains its own substances that "age" the body, and it can be assumed that the infusion of young blood dilutes the solution, reduces their concentration and, consequently, inhibits their action.
A group of researchers led by Irina Conboy from the University at Berkeley has been researching heterochronic parabiosis for a long time. This time they decided to test whether diluting the blood enough to achieve similar effects. For their work, they took two groups of mice: young (2-3 months) and old (22-24 months). Each animal underwent a complex procedure: blood was taken from him in small portions and changed to a saline solution with erythrocytes and platelets from an isochronous donor (that is, the same age as the recipient). As a result, each mouse lost about half of the blood plasma, while retaining all the blood cells. As a control, the scientists used a classical blood transfusion from an isochronous donor.
Six days after the procedure, the authors assessed the intensity of muscle regeneration after injury. It turned out that the regeneration index, as well as the diameter of new muscle fibers (the thicker, the stronger) in elderly animals after a single dilution of blood equaled that of young animals. Then the researchers checked whether there are similar properties in human blood. They took blood samples from patients before and after plasmapheresis, a common procedure for "cleaning" blood, which is used, for example, in autoimmune diseases. The authors treated mouse muscle cell cultures with these serum samples and found that before plasmapheresis, serum suppresses cell division, and after it, the number of dividing myocytes increases almost fourfold.
The muscles of elderly mice after isochronic blood exchange (OO) and dilution (ONBE). Figure A shows the comparative thickness of the fibers (top) and the expression of muscle cell markers (bottom). B – comparison of regeneration and fibrosis indices and fiber thickness in young and old animals after blood dilution (YNBE and ONBE, respectively). Drawings from an article in Aging.
The researchers obtained similar results for neurogenesis. They calculated the number of dividing cells in the hippocampus of mice and it turned out that dilution of blood allows old mice to catch up with young ones by this parameter. In young animals, blood dilution only insignificantly increased neurogenesis. The same thing happened in the liver: the indices of obesity and fibrosis – signs of tissue aging – in elderly mice decreased by half, although they did not equal those in young animals.
Thus, the effect of blood dilution was observed in derivatives of all three "layers of the body" (germ leaves): external – in the brain, internal – in the liver and intermediate – in the muscles. This means that heterochronic parabiosis can simply rid the old organism of the adverse effects of its own molecules, and not introduce something new. The list of such molecules that may need to be disposed of is quite large: there are many pro-inflammatory molecules and other signaling substances in it. However, the authors of the work admit that it's not just about dilution: a drop in the concentration of substances can trigger complex mechanisms of regulation based on the feedback principle, as a result of which the concentration will continue to decrease.
A model that describes the change in the concentration of substances in the blood during dilution. Hypothetical substances A, B and C trigger the production of themselves and inhibit the production of each other in the old organism.
If these assumptions are confirmed, then the means of "rejuvenation" of the new generation will not be ethically questionable, risky and expensive blood transfusion from young donors, but plasmapheresis, well known to doctors. However, it is too early to talk about its effectiveness before clinical trials.
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