Telomeres are being restored!
Chromosome shortening is reversibleElena Novoselova, STRF.ru
Somatic cells are devoid of telomerase activity, and the number of their divisions is limited.
This is the so-called "Hayflick limit", corresponding to 50-60 cell divisions. With each cell division, the telomeric portion of the chromosome shortens. There is a special enzyme – telomerase, which, using its own RNA matrix, completes telomeric repeats and lengthens telomeres. In most differentiated cells, telomerase is blocked, but it is active in stem, cancer and germ cells. It was for his work in the field of studying the role of telomerase group enzymes in protecting the ends of chromosomes from shortening that the Nobel Prize in Medicine and Physiology was awarded this year.
The study of the mechanisms by which it was possible to restore the normal length of telomeres in mouse cells can contribute to the effective treatment of such serious hereditary diseases as congenital dyskeratosis. In addition, the ability to regulate the activity of the telomerase complex will allow the development of new approaches to cancer therapy.
Congenital dyskeratosis is a genetic disease, which in its classical form is characterized by a triad of symptoms: pigmentation abnormality, nail dystrophy and leukoplakia (keratinization of the mucous membrane). Patients with congenital dyskeratosis have a high predisposition to the development of bone marrow insufficiency and tumors.
Mutations of genes (DKC1 and TERT) encoding components of the telomerase complex lead to the development of dyskeratosis, and the disease is now considered mainly as a defect of telomerase function. Thus, mutations of the TERT (telomerase reverse transcriptase) gene, responsible for the synthesis of reverse transcriptase, lead to a violation of chromosome length control and, as a consequence, to their incorrect rearrangement during cell division and genetic instability. Such cells are not viable and die quickly.
Researchers from the Ontario Cancer Institute (Toronto, Canada), led by Professor Lea Harrington, studied the mechanism of the occurrence and development of dyskeratosis in a line of transgenic mice with an artificially created mutation of the TERT gene, which made it possible to trace the inheritance of this mutation and its effect on the next 14 generations. What was the surprise of scientists when, after 12 generations, they began to observe the restoration of the normal function of the telomerase complex and the stabilization of the length of chromosomes. According to the authors, this was such a confusing observation that they had to repeat the experiments several more times until they were finally convinced of the ability of telomeres to recover.
Experts suggest the possibility of such a mechanism for maintaining the stability of chromosome length in the human body, which allows stem cells to be protected from telomerase erosion. In addition, the authors hope that in the near future they will be able to find a way to activate the process of restoring the length of chromosomes in people suffering from congenital dyskeratosis and vice versa, to regain control over cancer cells that do not have telomere shortening and their ability to divide is unlimited.
The results of these studies will be published in the journal Disease Models & Mechanisms.
Prepared based on EurekAlert! – Mice regain ability to extend telomeres suggesting potential for dyskeratosis congenita therapyPortal "Eternal youth" http://vechnayamolodost.ru