Immortality and eternal youth are provided by zinc fingers

Researchers at the US National Institute of Aging have found that the Zscan4 gene plays a key role in the ability of mouse embryonic stem cells to self-renew. These data, published on March 24 in the preliminary on-line version of the journal Nature in the article "Zscan4 regulates telomere elongation and genomic stability in ES cells", are of great importance for research conducted in the fields of aging, stem cell biology, regenerative medicine and oncology.

The protein product of this gene – zinc finger protein 494 – belongs to a group of proteins with so–called "zinc fingers", known for their ability to bind to a strictly defined sequence of nucleotides in DNA (for more information, see the note "Gene therapy with zinc fingers - simple, fast, accurate").

The uniqueness of embryonic cells is due not only to the ability to differentiate into almost all types of cells in the body, but also to the ability to form an unlimited number of full-fledged new (daughter) cells. Unlike them, cells of other types can only give rise to a limited number of generations of daughter cells, after which they lose the ability to function normally. This is partly due to the fact that the protective end sections of their chromosomes – telomeres – are shortened with each division. When telomeres reach a critical length, the cell, as a rule, dies, enters the phase of physiological aging or begins to divide with the formation of abnormal cells.

Until now, the mechanisms underlying the immortality of embryonic stem cells have remained a mystery to specialists. According to the currently dominant theory of "self-renewal", the daughter cells obtained during the division of embryonic cells are exact copies (as for the telomere length) of the parent cells. However, based on the data they obtained, the authors came to the conclusion that in reality the definitions of "rejuvenation" or "recovery" are more suitable for this process. Just as with the division of any other cells, the daughter cells formed during the division of embryonic cells have shorter telomeres. However, in these cells, the expression of the Zscan4 gene is activated – the synthesis of the corresponding protein, which, as it were, rejuvenates them, returning their unique properties to the cells.

This rejuvenation consists in restoring the length of telomeres using a recombination mechanism, when shorter telomeres interact with longer ones, which provides an increase in their length. After that, the Zscan4 gene is inactivated. This gene is not activated at every cell division, and only about 5% of embryo cells express it at any given time.

On the left are chromosomes with colored telomeres in the nucleus of a cell with the "silent" Zscan4 gene,
on the right are the chromosomes in the cell in which the expression of this gene is increased.

Currently, researchers are searching for similar mechanisms that provide the ability to unlimited division of human embryonic stem cells.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: Newly Discovered Gene Explains Mouse Embryonic Stem Cell Immortality.

25.03.2010