01 February 2022

Rejuvenating vesicles

A drug obtained from the organisms of young mice may briefly rejuvenate old ones

XX2 century

As they age, vertebrates, including humans, weaken, their risk of fractures increases, tissue regeneration worsens, age-related diseases develop. And many scientists are now searching for strategies that would delay and slow down the degenerative changes associated with aging. Recently, a team of researchers from Spain and the USA tried to inject small extracellular vesicles obtained from fatty mesenchymal stem cells of young animals intravenously into old animals and found an improvement in several functional parameters that usually change for the worse with age: the individuals who received therapy improved coordination of movements, grip strength, fatigue resistance, wool regeneration and kidney function.

Previous experiments on mouse parabiosis (when two animals are stitched together in such a way as to unite their circulatory systems) have shown that the factors present in the blood of a young organism are useful for an elderly person, including ridding him of certain factors associated with aging. Allogeneic transplantation of mesenchemal stem cells to severely weakened people for one reason or another has also shown promising results in terms of treating weakness. The regenerative abilities of stem cells are quite well known, but some modern studies have made it clear that the regenerative processes in the body as a result of the action of stem cells are triggered not only because these cells can trigger tissue regeneration after certain types of damage. It's also about the effect on the body of regulatory molecules emitted by stem cells, in particular, microRNAs contained in extracellular vesicles. It is remarkable that, unlike the stem cells themselves, the extracellular vesicles emitted by them are more stable, do not carry the risk of aneuploidy and are much less likely to undergo immune rejection. At the same time, their possible therapeutic potential is still poorly understood.

Scientists from the University of Valencia (Universidad de Valencia, Spain) and the American non-profit organization Clock Foundation, which studies the so-called epigenetic clock, taking into account all of the above, decided to test, first on mice, the rejuvenating potential of extracellular vesicles. They took a group of elderly mice, measured its total mass, checked the grasping strength of their limbs, tested the animals for fatigue resistance, and also — to control kidney function — measured the level of urea in blood plasma. In addition, to test the ability to regenerate the wool cover, each mouse had its fur shaved off on a small area of skin.

Then the elderly mice were divided into experimental and control groups, after which the animals from the experimental group received extracellular vesicles injected from young mice. 14 and 30 days after the injection, the scientists repeated the tests. And the difference between the mice treated and the control was obvious: the animals treated with vesicles of young mice showed an increase in grip strength, increased resistance to fatigue, their kidney function improved, and the shaved area on the skin was overgrown with hair (in the mice in the control group, it remained naked or almost naked). Curiously, however, 60 days after treatment, all the positive effects, except for the overgrown shaved area, disappeared — there were no significant differences between the experimental and control groups anymore. That is, the authors conclude, extracellular vesicles obtained from stem cells of young animals very noticeably reverse the epigenetic clock of elderly animals, strengthening their muscles, partially tidying up internal organs and changing their type of metabolism to "youth", but, unfortunately, this is only a temporary effect. And, of course, "additional research is needed" — to identify factors that can be obtained from stem cells and that can contribute to tissue regeneration and the fight against senile weakness.

The article by Sanz-Ros et al. Small extracellular vesicles from young mice prevent frailty, improve healthspan and decrease epigenetic age in old mice is published on the bioRxiv website.

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