[Epigenetic nature of ageing].
The idea proposed in this article is that a specific set of microRNAs expressing in stem cells can restore the initial profile of their epigenetic markers through RNAi-directed DNA methylation, and owing to that the pluripotent immortal status of these cells is supported unlimitedly and possibly minimum level of the mobile genomic elements activity is achieved. However, cell differentiation, starting with the earliest stages, must be accompanied with repression of genes of some microRNAs out of the primary set, otherwise these microRNAs would prevent expression of genes participating in the differentiation processes. Eventually, it results in that the cells slowly lose the repressive chromatin markers and this, sooner or later, will cause derepression of silent transposons and other mobile elements. This, accordingly, leads to the increase in DNA damage induced by these elements, and to following activation of cell systems of the DNA repair including mechanisms based on homologous recombination. In our opinion, these mechanisms cause not only DNA repair, but also unauthorized recombination on telomere capping structures, since they are pre-recombination structures. It is also possible that transposases in itself can initiate such recombination. As a result, the T-loops converse into rings and, accordingly, telomeres are shortened for the length of the lost circled DNA. This process can cause quick exhaustion of one or more cell telomeres and, therefore, subsequent senescence, cell cycle arrest and apoptosis of the cells, in which the illegitimate activation of recombination process becomes apparent. Apparently, large quantity of organism cells reaches with age the threshold of illegitimate activation of silent mobile genomic elements; subsequent apoptosis of most of these cells causes ageing as a biological phenomenon.
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D000818:Animals; D017209:Apoptosis; D016922:Cellular Senescence / Q000235:genetics*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004251:DNA Transposable Elements / Q000235:genetics; D044127:Epigenesis, Genetic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D034881:Nuclear Lamina / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D013234:Stem Cells / Q000502:physiology; D016615:Telomere / Q000235:genetics / Q000378:metabolism
D002843:Chromatin; D004251:DNA Transposable Elements; D035683:MicroRNAs; D034741:RNA, Small Interfering