Specific prediction of mortality by oxidative stress-induced damage to RNA vs. DNA in humans

Anders Jorgensen*, Ivan Brandslund, Christina Ellervik, Trine Henriksen, Allan Weimann, Per Kragh Andersen, Henrik E Poulsen

*Corresponding author for this work
2 Citations (Scopus)

Abstract

Modifications of nucleic acids (DNA and RNA) from oxidative stress is a potential driver of aging per se and of mortality in age-associated medical disorders such as type 2 diabetes (T2D). In a human cohort, we found a strong prediction of all-cause mortality by a marker of systemic oxidation of RNA in patients with T2D (n = 2672) and in nondiabetic control subjects (n = 4079). The finding persisted after the adjustment of established modifiers of oxidative stress (including BMI, smoking, and glycated hemoglobin). In contrast, systemic levels of DNA damage from oxidation, which traditionally has been causally linked to both T2D and aging, failed to predict mortality. Strikingly, these findings were subsequently replicated in an independent general population study (n = 3649). The data demonstrate a specific importance of RNA damage from oxidation in T2D and general aging.

Original languageEnglish
Article numbere13839
JournalAging Cell
Volume22
Issue number6
Pages (from-to)e13839
ISSN1474-9718
DOIs
Publication statusPublished - Jun 2023

Keywords

  • Aging/genetics
  • DNA Damage/genetics
  • DNA/metabolism
  • Diabetes Mellitus, Type 2/genetics
  • Humans
  • Oxidative Stress
  • RNA/genetics

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