25 March 2010

How to achieve immortality?

Swedish scientists from Umea University, working under the guidance of Professor Goran Roos, have demonstrated that under certain conditions cells are able to achieve a state of immortality (immortalization) by gradually changing the expression of genes that control the processes of DNA repair, as well as cell growth and division. The researchers also found that the activation of the telomerase enzymatic complex, which is necessary to ensure unlimited cell division, occurs at the final stages of this process.

The results of the study are published in the April issue of the journal Aging Cell in the article Sofie Degerman et al. "Telomerase upregulation is a post-crisis event during senescence bypass and immortalization of two Nijmegen breakage syndrome T cell cultures".

An important role in maintaining the genetic stability of the cell is played by the end sections of chromosomes – telomeres. In normal cells, telomeres shorten with each division, and when they reach a certain length, the cells stop dividing. In the presence of certain genetic mutations, cells continue to divide despite the continued shortening of telomeres. However, when telomeres reach a critical length, a so-called crisis develops, manifested by an imbalance of gene activity and mass cell death. In some cases, cells survive this crisis and acquire the ability to divide indefinitely. In earlier studies, this transition from a state of crisis to a state of immortalization was associated with the activation of telomerase, an enzymatic complex capable of restoring telomere length and stabilizing the genome. It is also a well-known fact that telomerase is active in malignant cells.

As part of their work, the authors repeatedly analyzed the state of lymphocytes cultured in an incubator until all surviving cells reached the state of immortality. Usually, certain genetic manipulations are performed on cells to achieve immortalization, but in this work, lymphocytes became immortal spontaneously. This unusual phenomenon is similar to the processes leading to the development of malignant diseases such as leukemia.

The study of the state of cells showed that initially their telomeres, as expected, shortened with each division, and after a certain period of time, the cells entered a crisis stage characterized by mass cell death. At the same time, no telomerase activity was recorded in the cells that survived the crisis and achieved immortalization. The authors found that the expression of genes suppressing telomerase activity is reduced in such cells, but this does not lead to activation of the enzymatic complex, which occurs later as a result of activation of positive regulation factors. The result of this is the subsequent elongation and stabilization of telomeres. Gene expression analysis showed that the cells that survived the crisis had mutations in genes that play a key role in the processes of repairing DNA damage, as well as cell growth and division.

The data obtained by the authors shed new light on the complex of mechanisms that ensure cell immortalization. This new information will help specialists in studying the etiology of various malignant diseases, primarily leukemia.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: New Findings About How Cells Achieve Eternal Life.


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