Oxidative stress response and Nrf2 signaling in aging

Free Radic Biol Med. 2015 Nov;88(Pt B):314-336. doi: 10.1016/j.freeradbiomed.2015.05.036. Epub 2015 Jun 9.


Increasing oxidative stress, a major characteristic of aging, has been implicated in a variety of age-related pathologies. In aging, oxidant production from several sources is increased, whereas antioxidant enzymes, the primary lines of defense, are decreased. Repair systems, including the proteasomal degradation of damaged proteins, also decline. Importantly, the adaptive response to oxidative stress declines with aging. Nrf2/EpRE signaling regulates the basal and inducible expression of many antioxidant enzymes and the proteasome. Nrf2/EpRE activity is regulated at several levels, including transcription, posttranslation, and interactions with other proteins. This review summarizes current studies on age-related impairment of Nrf2/EpRE function and discusses the changes in Nrf2 regulatory mechanisms with aging.

Keywords: Aging; Antioxidant; Free radicals; Nrf2; Oxidative stress; Transcription factor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Antioxidants / metabolism
  • Gene Expression Regulation / physiology*
  • Humans
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / physiology*
  • Signal Transduction / physiology*


  • Antioxidants
  • NF-E2-Related Factor 2