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Aging reduces genetic silencing of transposable elements (TEs), but genomic TE copies may not increase. Small RNA and RNA interference pathways appear to mitigate TE expansion during aging in Drosophila.

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Area of Science:

  • Genetics
  • Molecular Biology
  • Aging Research

Background:

  • Genetic mechanisms suppressing transposable elements (TEs) weaken with age.
  • Increased TE expression is observed in aged animals, raising questions about genomic copy number changes.

Purpose of the Study:

  • To investigate whether increased TE expression during aging leads to more genomic TE copies.
  • To explore the role of small RNA and RNA interference (RNAi) pathways in mitigating TE expansion.
  • To identify potential interventions to suppress age-associated TE expression and extend lifespan.

Main Methods:

  • Quantified TE Landscapes (TLs) using whole genome sequencing in young and aged Drosophila.
  • Analyzed TLs in whole flies and dissected brains.
  • Developed improved sequencing methods for extra-chromosomal DNA circles (eccDNAs).

Main Results:

  • TE Landscapes were quantified in young and aged Drosophila, including wild-type and mutant strains.
  • The study validated methods for detecting new TE insertions in aging genomes, particularly when RNAi pathways are compromised.
  • Improved methods for quantifying eccDNAs revealed them as an additional source of aging-associated TE copies.

Conclusions:

  • Small RNA and RNAi pathways may mitigate genomic TE expansion despite increased TE transcription during aging.
  • Knocking down PAF1, a transcription elongation factor, may enhance TE suppression and extend lifespan in aging Drosophila.
  • Genetic background can influence TE dynamics during aging.