Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 28 Kommunisticheskaya st., 167982 Syktyvkar, Russian Federation.
Laboratory of Geroprotective and Radioprotective Technologies, Institute of Biology, Komi Science Center, Ural Branch, Russian Academy of Sciences, 28 Kommunisticheskaya st., 167982 Syktyvkar, Russian Federation; Laboratory of Genetics and Epigenetics of Aging, Russian Clinical Research Center for Gerontology, Pirogov Russian National Research Medical University, Moscow 129226, Russian Federation; Longaevus Technologies, London, UK.
Ageing Res Rev. 2023 Apr;86:101881. doi: 10.1016/j.arr.2023.101881. Epub 2023 Feb 10.
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.
转座元件 (TEs) 是真核基因组的重要组成部分。体细胞转座在衰老、癌变和其他与年龄相关的疾病中的作用已经确定。本综述讨论了 TEs 的基本特性及其与细胞过程的复杂相互作用，这些相互作用对于理解其活性对生物体遗传和表观遗传的多种影响至关重要。TEs 与重组、复制、修复和染色体调节的相互作用；TEs 维持自身活性和抑制之间平衡的能力、TEs 在创造新的或替代基因、编码/非编码 RNA 的表达以及在 DNA 损伤和调节网络修饰中的作用的综述。评估了去抑制的 TEs 在不同生物体的个体细胞/组织中对年龄相关效应的贡献。讨论了有关 TEs 活性的应激相关的矛盾信息以及与 TEs 相关的衰老机制理论。一方面，对胁迫的转座活性可以导致生物体获得对种群水平进化具有重要意义的适应性创新。另一方面，TE 的表达会导致个体水平的寿命缩短和应激耐受能力降低。突出了 TEs 对生殖系和体的衰老过程的影响的具体特征及其在细胞中的调节方式。指出了考虑正常人类和动物组织中的体细胞突变的最新结果，重点是它们可能的功能后果。在衰老的背景下，分析了体细胞 TE 激活与维持异染色质和长寿调节所需蛋白质数量的年龄相关变化之间的相关性。本综述的一个原创特点是讨论了不仅基于 TEs 插入的影响及其对生殖细胞动力学和体细胞基因组的相关后果，还讨论了转座子和逆转座子介导的结构基因组变化之间的差异，以及与衰老和各种与年龄相关的病理学相关的可能表型特征。基于对已发表数据的分析，提出了一个关于 TEs 的数量、组成和分布的物种特异性特征对不同动物基因组衰老动态的影响的假设。
