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Repetitive element transcript accumulation is associated with inflammaging in humans.

Meghan E Smith1, Devin Wahl1, Alyssa N Cavalier1

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Area of Science:

  • Genomics
  • Immunology
  • Aging Research

Background:

  • Chronic, low-grade inflammation, or inflammaging, is linked to aging and associated functional decline.
  • Repetitive elements (RE) are increasingly implicated in inflammaging via innate immune activation, but human data are limited.

Purpose of the Study:

  • To investigate the relationship between RE transcripts, inflammation, and aging in humans.
  • To explore the impact of aging and aerobic exercise on RE epigenetic regulation and expression.

Main Methods:

  • Transcriptomic and whole-genome bisulfite sequencing in middle-aged and older adults.
  • Analysis of serum inflammatory markers (interleukin-6) and gene expression.
  • Assessment of RE chromatin accessibility in a secondary dataset.

Main Results:

  • RE transcript levels positively correlate with innate immune sensor gene expression and serum interleukin-6.
  • Aging is associated with RE hypomethylation and increased RE transcripts.
  • Aerobic exercise reduces RE transcript levels and increases RE methylation in older adults.
  • Age-related changes in RE chromatin accessibility were observed.

Conclusions:

  • Age-related accumulation of RE transcripts may contribute to inflammaging in humans.
  • Epigenetic changes, including altered DNA methylation and chromatin accessibility, likely underlie RE dysregulation with aging.
  • Aerobic exercise shows potential for modulating RE activity and mitigating age-related inflammation.