Transposable elements and their role in aging

Abstract

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.

Keywords: Age-related pathologies; Aging; Derepression; Germline cells; Somatic genome; Transposable elements; Transpositions.