Do you want to get younger? Simulate pregnancy!
Scientists at the Hebrew University in Jerusalem, working under the guidance of Professor Yehudit Bergman, have found that pregnancy increases the regenerative potential of the liver of mice. The data they obtained, published on March 15 in the journal Genes and Development in the article "Pregnancy restores the regenerative capacity of the aged liver via activation of an mTORC1-controlled hyperplasia/hypertrophy switch", can shed light on the mechanisms underlying the completely unrelated pregnancy process – aging.
The attention of researchers who initially studied the epigenetics of embryonic stem cells was attracted by the question of the ability of tissues to regenerate. Five years ago, they published the first results of their work in this area. According to their observation, the regenerative abilities of muscle progenitor cells of old animals can be stimulated by parabiosis, an experimental technique consisting in connecting the circulatory systems of two animals (in this case, old and young) and allowing one organism to take advantage of factors circulating in the blood of another. (This work is mentioned in the article "Young blood returns youth to the elderly.")
The term "parabiosis" (from the Greek para – near, near and bios – life) is used to refer to two completely different concepts.
The Russian physiologist N. E. Vvedensky named the reversible state of the cell that he discovered (upon termination of the damaging agent), the borderline between life and death.
Parabiosis is also called (as in this case) the artificial connection of two or more organisms through the circulatory and lymphatic systems to study the mutual effects of hormones and other metabolites.
Based on the fact that pregnancy to a certain extent is also a parabiosis (a combination of two organisms), the authors tested the ability of the liver of elderly (10-12 months) pregnant and non-pregnant mice to regenerate after removal of two thirds of the organ. The results of the observation exceeded all expectations: the liver of non-pregnant animals recovered only to about 50% of the original volume, whereas in pregnant mice the volume of the restored organ was up to 96% of the original. Nine out of 19 non-pregnant mice died after surgery, while only two mice died in a group of 22 pregnant animals. Unlike old mice, young animals (3 months) demonstrated a pronounced ability of the liver to regenerate regardless of the presence of pregnancy.
At first, the researchers assumed that the restoration of liver size during pregnancy occurs due to cell division, however, the use of a proliferation marker showed that on the second or third days after surgery (when the maximum rate of liver cell division was observed in non-pregnant animals), the liver cells of pregnant mice practically did not divide. Instead, they noticeably increased in size. These results indicate that the mechanisms of liver regeneration in pregnant and non-pregnant states are very different.
In order to study these processes in more detail, the authors blocked the Akt/mTORC1 signaling mechanism in animal liver cells, which plays an important role in the process of cell growth. This stopped the growth of liver cells of pregnant animals and at the same time slightly stimulated their division, but this was not enough for significant organ recovery.
Taking into account the fact that pregnancy changes the model of liver regeneration, as well as the fact that aging negatively affects the regeneration processes, scientists decided to try to make the liver of old mice work like the liver of pregnant animals. To do this, they injected old animals (18-24 months old) with a compound that activates the Akt/mTORC1 signaling mechanism, after which they removed two-thirds of their liver. As a result, none of the nine mice of the experimental group died, while the operation proved fatal for four of the nine animals of the control group.
To date, experts have not yet agreed on the real value of the information received and its possible clinical significance, but they recognize the exclusivity of the observed phenomenon. They also note that it is unclear to what extent the observed increase in cell size restores liver function and whether an approach based on modeling the Akt/mTORC1 signaling mechanism will have a positive effect on the male liver.
Currently, the authors are working on deciphering the molecular mechanisms underlying the phenomenon they observed. In addition, they are trying to find out whether pregnancy has a similar effect on the regenerative functions of other organs.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Scientist: Pregnancy helps liver?
19.03.2010