The paradoxical role of thioredoxin on oxidative stress and aging

Geneva M. Cunningham, Madeline G. Roman, Lisa C. Flores, Gene B. Hubbard, Adam B. Salmon, Yiqiang Zhang, Jonathan Gelfond, Yuji Ikeno

Research output: Contribution to journalReview article

31 Scopus citations

Abstract

Abstract In spite of intensive study, there is still controversy about the free radical or oxidative stress theory of aging, particularly in mammals. Our laboratory has conducted the first detailed studies on the role of thioredoxin (Trx) in the cytosol (Trx1) and in mitochondria (Trx2) on oxidative stress and aging using unique mouse models either overexpressing or down-regulating Trx1 or Trx2. The results generated from our lab and others indicate that: (1) oxidative stress and subsequent changes in signaling pathways could have different pathophysiological impacts at different stages of life; (2) changes in redox-sensitive signaling controlled by levels of oxidative stress and redox state could play more important roles in pathophysiology than accumulation of oxidative damage; (3) changes in oxidative stress and redox state in different cellular compartments (cytosol, mitochondria, or nucleus) could play different roles in pathophysiology during aging, and their combined effects show more impact on aging than changes in either oxidative stress or redox state alone; and (4) the roles of oxidative stress and redox state could have different pathophysiological consequences in different organs/tissues/cells or pathophysiological conditions. To critically test the role of oxidative stress on aging and investigate changes in redox-sensitive signaling pathways, further study is required.

Original languageEnglish (US)
Article number6925
Pages (from-to)32-38
Number of pages7
JournalArchives of Biochemistry and Biophysics
Volume576
DOIs
StatePublished - Jun 2 2015

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Keywords

  • Aging
  • Cancer
  • Knockout mouse
  • Oxidative stress
  • Thioredoxin
  • Transgenic mouse

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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