29 November 2010

Rejuvenation by telomerase activation: article in Nature

Telomere restoration restored youth to cellsNadezhda Markina, Infox.ru
Biologists have experimentally confirmed the way in which youth can be restored to all tissues of the body.

They managed to start the work of an enzyme that unscrews back the clock of cellular time.

Scientists from the Harvard Medical School (Boston, USA) managed to overcome the aging of organs and tissues in mice by superstructuring telomeres in stem cells. Telomeres – repeats of short sequences of nucleotides at the ends of chromosomes – are considered as a marker of aging. With each cell division, they shorten due to the inability of the DNA polymerase enzyme to synthesize a copy of DNA from the very end. There remains an unlinked end that does not fall into the daughter cell.

Telomeres can be built up to the previous length with the help of a special enzyme – telomerase, which works in stem and germ cells. Telomerase attracts a lot of attention of specialists dealing with the problems of aging. But it has not yet been possible to use the telomerase mechanism to reverse the degradation of tissues.

Aging MutantsRonald A. DePinho and his team worked on mutant mice.

Their telomerase did not work even in those cells in which it should – in stem and germ cells. The fibroblasts isolated from them could divide no more than four to five times, after which they degraded. And the mice themselves showed signs of aging at a very young age: the testes and spleen degraded, the ability to reproduce disappeared. Neurogenesis has slowed down in the brain: the number of neural stem cells and their transformation into neurons and glial cells – oligodendrocytes has decreased. And due to the lack of the latter, the long processes of neurons - axons have lost part of their insulating myelin sheaths. As a result, the brain of mutants became smaller and lighter compared to the brain of normal mice. In addition, the mutants' sense of smell was impaired (as usually happens in old animals), as the olfactory epithelium degraded.

Atrophy is reversibleDegeneration was reversed when scientists biochemically restored telomerase activity in cells.

In culture, this led to the elongation of telomeres and the resumption of cell divisions. The cells were able to share at least twenty more times. At the same time, tissues in organs with actively multiplying cells began to recover in mice: signs of apoptosis in the cells of the testes and intestinal epithelium disappeared, the testes and spleen increased in size. Neural stem cells began to multiply more often in the brains of such mice.

Another process went on – neural cells began to turn into neurons and glial cells. Neurons have grown myelin sheaths on their axons, which is why the weight of the brain has increased by an average of 16%. Finally, in experiments with learning to smell stimuli, biologists were convinced that telomerase activity restored the impaired sense of smell.

The experiment shows, the authors believe, that adult stem cells in a dormant state can be returned to active life and reproduction if telomere restoration is activated. In this experiment, mutant mice with non-functioning telomerase served as a model, but the same thing happens with age-related changes in the body. The work demonstrated the fundamental possibility of tissue rejuvenation by activating telomerase. Although you have to be very careful on this path, since telomerase is active in cancer cells. In this experiment, scientists did not encounter cancerous tissue degeneration, but this possibility cannot be excluded.

An article on the method of rejuvenation of mice (Mariela Jaskelioff et al., Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice) was published in Nature; in Nature News – a retelling of the results of the work in a language understandable to non-specialists (Telomerase reverses aging process: Dramatic rejuvenation of prematurely aged mice hints at potential therapy).

Portal "Eternal youth" http://vechnayamolodost.ru29.11.2010


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