Transposable elements and their role in aging.

Transposable elements (TEs) are an important part of eukaryotic genomes. The role of somatic transposition in aging, carcinogenesis, and other age-related diseases has been determined. This review discusses the fundamental properties of TEs and their complex interactions with cellular processes, which are crucial for understanding the diverse effects of their activity on the genetics and epigenetics of the organism. The interactions of TEs with recombination, replication, repair, and chromosomal regulation; the ability of TEs to maintain a balance between their own activity and repression, the involvement of TEs in the creation of new or alternative genes, the expression of coding/non-coding RNA, and the role in DNA damage and modification of regulatory networks are reviewed. The contribution of the derepressed TEs to age-dependent effects in individual cells/tissues in different organisms was assessed. Conflicting information about TE activity under stress as well as theories of aging mechanisms related to TEs is discussed. On the one hand, transposition activity in response to stressors can lead to organisms acquiring adaptive innovations of great importance for evolution at the population level. On the other hand, the TE expression can cause decreased longevity and stress tolerance at the individual level. The specific features of TE effects on aging processes in germline and soma and the ways of their regulation in cells are highlighted. Recent results considering somatic mutations in normal human and animal tissues are indicated, with the emphasis on their possible functional consequences. In the context of aging, the correlation between somatic TE activation and age-related changes in the number of proteins required for heterochromatin maintenance and longevity regulation was analyzed. One of the original features of this review is a discussion of not only effects based on the TEs insertions and the associated consequences for the germline cell dynamics and somatic genome, but also the differences between transposon- and retrotransposon-mediated structural genome changes and possible phenotypic characteristics associated with aging and various age-related pathologies. Based on the analysis of published data, a hypothesis about the influence of the species-specific features of number, composition, and distribution of TEs on aging dynamics of different animal genomes was formulated.

Involvement of DNA Repair Genes and System of Radiation-Induced Activation of Transposons in Formation of Transgenerational Effects.

The study of the genetic basis of the manifestation of radiation-induced effects and their transgenerational inheritance makes it possible to identify the mechanisms of adaptation and possible effective strategies for the survival of organisms in response to chronic radioactive stress. One persistent hypothesis is that the activation of certain genes involved in cellular defense is a specific response of the cell to irradiation. There is also data indicating the important role of transposable elements in the formation of radiosensitivity/radioresistance of biological systems. In this work, we studied the interaction of the systems of hobo transposon activity and DNA repair in the cell under conditions of chronic low-dose irradiation and its participation in the inheritance of radiation-induced transgenerational instability in Drosophila. Our results showed a significant increase of sterility and locus-specific mutability, a decrease of survival, fertility and genome stability (an increase the frequency of dominant lethal mutations and DNA damage) in non-irradiated F1/F2 offspring of irradiated parents with dysfunction of the mus304 gene which is responsible for excision and post-replicative recombination repair and repair of double-stranded DNA breaks. The combined action of dysfunction of the mus309 gene and transpositional activity of hobo elements also led to the transgenerational effects of irradiation but only in the F1 offspring. Dysfunction of the genes of other DNA repair systems (mus101 and mus210) showed no visible effects inherited from irradiated parents subjected to hobo transpositions. The mei-41 gene showed specificity in this type of interaction, which consists in its higher efficiency in sensing events induced by transpositional activity rather than irradiation.

Genetic mechanisms of formation of radiation-induced instability of the genome and its transgenerational effects in the descendants of chronically irradiated individuals of Drosophila melanogaster.

The article is devoted to the study of the role of intracellular mechanisms in the formation of radiation-induced genetic instability and its transgenerational effect in cells of different tissues of the descendants of Drosophila melanogaster mutant strains whose parents were exposed to chronic radiation (0.42 and 3.5 mGy/h). The level of DNA damage (alkali-labile sites (ALS), single-strand (SSB) and double-strand (DSB) breaks) in cells of somatic (nerve ganglia, imaginal discs) and generative (testis) tissues from directly irradiated animals and their unirradiated offspring was evaluated. Confident transgenerational instability (on the level of ALSs and SSBs), observed only in somatic tissues and only at the higher dose rate, is characteristic for mus209 mutant strains defective in excision repair and, less often, for mus205 and mus210 mutant strains. The greatest manifestation of radiation-induced genetic instability was found in evaluating the DSBs. Dysfunction of the genes mus205, mus304, mei-9 and mei-41, which are responsible for postreplicative repair, excision repair, recombination and control of the cell cycle, affects transgenerational changes in the somatic tissues of the offspring of parents irradiated in both low and high dose rates. In germ cells, the key role in maintaining genetic stability under chronic irradiation is played by the non-recombination postreplication repair mus101 gene. We revealed the tissue specificity of the radiation-induced effects, transgenerational transmission and accumulation of DNA damage to descendants of chronically irradiated animals.

Effects of ionizing radiation at Drosophila melanogaster with differently active hobo transposons.

Purpose: The role of transposable elements in formation of radiobiological effects is understudied and contradictory. The aim of this study was to investigate the response of Drosophila melanogaster to irradiation depending on the level of activity hobo transposons and the role of hobo transposons in formation of ionizing radiation late effects.Materials and methods: The individuals of Drosophila melanogaster with different level activity of hobo-elements were exposed to acute irradiation in doses of 1-100 Gy at early ontogenesis stages. The reaction of individuals to exposure was studied using the larvae survival rate, morphological parameters of reproduction system, DNA damage rate, and mutability of mini-white locus.Results: We found the pronounced linear deferred effects of irradiation for animals with a high activity level of full-size hobo copies. The radiosensitivity of individuals with a mean level of activity transposon was whether higher or did not differ from the radiosensitivity of animals with a low activity hobo.Conclusion: The obtained results suggest that full-size hobo-elements with a high activity level (less often with a mean activity level) are responsible for delayed deleterious irradiation effects.