Senescent cells showed opposing regulation of retroelements and , with LINE-1 activity rising as APOBEC3B declined.
Evidence
Sequencing dataset analyses, Ribo-seq profiling, and validation experiments examined LINE-1/Alu regulation in replicative and oncogene-induced senescent cells.
Caveat
The work is cell- and dataset-based and supports a mechanistic link in models rather than direct organism-level aging outcomes.
Simplified
Long Interspersed Nuclear Elements-1 (LINE-1 or L1) make up approximately 21% of the human genome, with some L1 loci containing intact open reading frames (ORFs) that facilitate retrotransposition. Because retrotransposition can have deleterious effects leading to mutations and genomic instability, L1 activity is typically suppressed in somatic cells through transcriptional and post-transcriptional mechanisms. However, L1 elements are derepressed in senescent cells causing age-associated inflammation. Despite the recognition of L1 activity as a hallmark of aging, the underlying molecular mechanisms governing L1 derepression in these cells are not fully understood. In this study, we employed high throughput sequencing datasets and validated our findings through independent experiments to investigate the regulation of L1 elements in senescent cells. Our results reveal that both replicative and oncogene-induced are associated with reduced expression of the cytidine deaminase , a known suppressor of L1 retrotransposition. Consequently, senescent cells exhibited diminished levels of C-to-U editing of full-length L1 elements. Moreover, Ribo-seq profiling indicated that progression to senescence is not only associated with increased L1 transcription, but also translation of L1 ORFs. In summary, our results suggest that the depletion of APOBEC3B contributes to enhanced activity of L1 in senescent cells and promotion of L1-induced DNA damage and aging.
Key numbers
68%
Decrease in Expression
Reduction in levels in presenescent, telomerase-negative cells.
8×
Editing Frequency Reduction
Editing frequency of the youngest subfamilies in senescent cells compared to non-senescent cells.
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