Abstract
SummaryDespite its medical, social, and economic significance, understanding what primarily causes aging, that is, the mechanisms of the aging process, remains a fundamental and fascinating problem in biology. Accumulating evidence indicates that a small RNA‐based gene regulatory machinery, the Piwi‐piRNA pathway, represents a shared feature of nonaging (potentially immortal) biological systems, including the germline, somatic cancer stem cells, and certain ‘lower’ eukaryotic organisms like the planarian flatworm and freshwater hydra. The pathway primarily functions to repress the activity of mobile genetic elements, also called transposable elements (TEs) or ‘jumping genes’, which are capable of moving from one genomic locus to another, thereby causing insertional mutations. TEs become increasingly active and multiply in the genomes of somatic cells as the organism ages. These characteristics of TEs highlight their decisive mutagenic role in the progressive disintegration of genetic information, a molecular hallmark associated with aging. Hence, TE‐mediated genomic instability may substantially contribute to the aging process.
Highlights
transposable elements (TEs) are capable of moving from one genomic locus to another, frequently generating insertional mutations in functional DNA regions (Malone & Hannon, 2009; Levin & Moran, 2011). These highly repetitive genetic elements are effectively repressed by the activity of the Piwi-piRNA pathway in nonaging germline and somatic cells
TE-derived mRNAs through processing endogenous double-stranded RNA structures (Ghildiyal et al, 2008). In certain organisms, such as plants that dispense with the Piwi-piRNA pathway, the siRNA-mediated silencing system appears to act as the main defense mechanism against the mobilization of TEs in both soma and germline
The repair and maintenance mechanisms are likely to be effective in the soma and germline in eliminating damages produced by metabolic and environmental factors, as well as those caused by transpositionindependent mutations that occur at a nearly constant rate throughout the lifespan (Fig. 2)
Summary
It is active in various tumorous cell lines (reviewed by Ross et al, 2014), implying that nonaging somatic cancer stem cells adopt certain germline-specific characteristics, that is, some extent of soma-to-germline transformation, including the activity of the Piwi-piRNA pathway and an unlimited proliferation capacity. These highly repetitive genetic elements are effectively repressed by the activity of the Piwi-piRNA pathway in nonaging germline and somatic cells.
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