19 February 2018

Forever young cells

Researchers from the University of Michigan, working under the guidance of Dr. Yukiko Yamashita, have identified a genetic trick that allows stem cells that give rise to sperm to remain young for many generations. Certain sections of the genome of fruit flies-drosophila shorten with age. However, as the authors managed to find out, certain reproductive cells can repair this defect.

As part of their study, the authors studied working genes encoded in ribosomal DNA (rDNA). These genes encode instructions for the synthesis of proteins that form ribosomes – cellular structures that ensure the synthesis of all proteins necessary for the body according to instructions encoded in RNA molecules.

To synthesize a sufficient number of ribosomes, the cell needs a large amount of rDNA. Most of the genes of an organism are limited to one genetic localization, but rDNA genes are repeated many times in different regions of the genome. In humans, for example, five chromosomes have sections of rDNA genes, while each of the sections contains hundreds of duplicate copies. This genetic repetition allows the cell to synthesize enough protein material to form ribosomes.

However, such a large number is associated with certain problems. In the process of division, cells can make mistakes when copying repetitive sections of DNA. As a result, some copies are lost, with each cycle of division they actually fall out of the chromosome.

Previously, this mechanism was associated exclusively with the aging of unicellular yeast. However, the role of rDNA in the aging of multicellular organisms has remained a mystery until now. The authors analyzed the rDNA genes in the stem cells of the seminal glands of fruit flies. These cells, known as germ stem cells, are capable of dividing indefinitely with the formation of a copy of the mother cell and sperm.

In drosophila, the rDNA gene chains are located on the X and Y chromosomes. The researchers found that older males have fewer rDNA genes on the Y chromosome than younger ones. Moreover, apparently, this rDNA deficiency is transmitted from generation to generation. Old males (older than 40 days) passed on Y chromosomes with a reduced number of rDNA genes to their offspring. As a result, their male offspring had fewer copies of rDNA than individuals born from eggs fertilized by young males.

However, later the authors revealed an unexpected mechanism. In many cases, the lost part of the rDNA was spontaneously restored. By about 10 days of age, the number of rDNA genes in young males of both groups became comparable. This rejuvenation of rDNA in the embryonic stem cells of young males may be a critical mechanism that ensures the preservation of the potential of these cells from generation to generation. To date, it is still unclear whether anything similar is happening in the ovaries.

Despite the need for a large amount of further research, Dr. Yamashita suggests that a similar "reset" can occur in certain types of human cells, such as stem and cancer cells.

Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the article by Lu et al. Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells, published in the journal eLife.


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