The size of the cells can vary surprisingly from one species to another. Phytoplankton cells measure approximately one micron, while frog oocytes can reach one millimeter. Even within the same organism, the sizes are completely different. Human neurons are gigantic compared to tiny red blood cells. But the scenario changes radically if we look at a single tissue, since its cells must maintain a particular size so that an efficient function can be exercised. The abstract of a study published in Science Advances begins by saying that “stem cells are remarkably small.” After this first sentence comes an approach that is not trivial: we do not know if this small size is important for the function of stem cells. The increase in size of hematopoietic stem cells (precursors of blood cells) is associated with a decrease in their functions. Being larger there is less proliferation of them and the metabolism is altered. Size matters, but in this case a small size, let’s not be misconceived.
The researchers came up with the finding that blood stem cells tend to increase in size as they age. “We have discovered cell enlargement as a new in vivo aging factor, now we can explore whether we can treat said cell enlargement to delay aging and related diseases”, explained Jette Legefeld, researcher at the University of Helnsinki and a of the 19 signatories of the study. Legefeld was a postdoc at MIT and is the main author of the article Cell size is a determinant of stem cell potential during aging .
Since the 1960s, we have known that human cells grown in a laboratory dish acquire enormous sizes, towards a state of aging in which they do not divide. Every time there is damage to the DNA molecule, division stops to repair the damage. In this process the cell grows a little more. Until now it was thought that enlargement was a side effect of aging, but … what about the other way around? Cell size could cause age-related loss of function.
The researchers damaged stem cells to see what the effect was. They used two types of samples: cells without any treatment and cells that were given a substance called rapamycin. The damage caused to DNA caused an increase in the size of hematopoietic cells that did not receive treatment, while rapamycin prevented the increase in size in those that were treated with it. From here, they wanted to measure the functionality of both sets of cells, injecting them into mice that had had their blood stem cells removed. The result is what you’d expect if you’ve read this far: Stem cells that were enlarged by DNA damage were unable to repopulate the blood cells of the mice. The others did, those that retained their size, that is, the cells that received rapamacin were able to repopulate the mouse’s blood cells despite having suffered DNA damage.
In another experiment, the researchers produced genetic mutations in order to reduce the size of cells that had been enlarged for reasons of age in the older mice. They found that when stem cells returned to their original size, they regained their regenerative potential and behaved like younger stem cells. Therefore, it is a double discovery: the enlargement of the cells produces aging and the functionality of a cell damaged by size can be restored by returning it to its original size. Something similar to the cake from Alice in Wonderland in which you could read “Eat me”.
Some mice were treated with rapamycin from an early age and it was found that enlargement of their blood stem cells was prevented. Rapamycin is a drug used to inhibit the growth of some cancers and to prevent rejection of transplanted organs. Lengefeld is enthusiastic: “If we find specific drugs to make large blood stem cells small again, we could test whether they improve the health of people with blood system problems, such as anemia or lowered immune systems. , or maybe even people with leukemia ”. The study could be extended to intestinal stem cells, as the researchers also demonstrated the relationship between aging and increase in size in these types of cells.
Rapamycin or sirolimis is a macrocyclic antibiotic discovered in 1965 that is isolated from a bacterium found in the soil of Rapa Nui, on Easter Island. The bacterium is Streptomyces hygroscopicus that inhibits the growth of some fungi such as Candida albicans , Microsporum gypseum and Trichophyton granulosum . An article had already been published in 2009 in Nature ( Rapamycin fed late in life extends lifespan in genetically heterogeneous mice ) in which it was shown that with this drug the life of mice could be prolonged by up to 38%. The new study published in Science Advance has taken a further step towards understanding this fact. Somehow rapamycin has the power to stop the biological clock and even make time go backwards. A candidate for the elixir of eternal youth.
