Modulation of glutathione and thioredoxin systems by calorie restriction during the aging process

Exp Gerontol. 2003 May;38(5):539-48. doi: 10.1016/s0531-5565(03)00005-6.


Accumulating evidence strongly suggests that oxidative stress underlies aging processes and that calorie restriction (CR) retards aging processes, leading to an extended lifespan for various organisms. Recent studies revealed that the anti-aging action of CR depends on its anti-oxidative mechanism. However, at present, the status of glutathione (GSH) and thioredoxin (Trx) system, two major thiol redox systems in animal cells during aging and its modulation by CR has not fully been explored. The purpose of this study is two-fold: one, to determine whether these two systems in rat kidney are altered as a consequence of aging; two, to determine whether these systems can be modulated by anti-oxidative CR. The results of our study showed that GSH and GSH-related enzyme activities decreased with age in ad libitum (AL)-fed rats, while CR rats consistently showed resistance to decreases in these activities. Data from the present data further showed that while Trx and Trx reductase (TrxR) in cytoplasm decrease with age in AL-fed rats, CR prevents these decreases. In contrast, we also found that the nuclear translocation of the redox regulators, Trx and Ref-1, increase with age, which was suppressed in CR rats. Therefore, increases in nuclear Trx and Ref-1 during aging may result in the up-regulation of redox-sensitive transcription factors, such as NF-kappaB or AP-1, via the interaction of Ref-1 and Trx in a redox-dependent manner. Our conclusion is that a redox imbalance occurs during aging and that redox changes are minimized through the anti-oxidative action of CR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology*
  • Animals
  • Blotting, Western / methods
  • Caloric Restriction / methods*
  • Carbon-Oxygen Lyases / genetics
  • DNA-(Apurinic or Apyrimidinic Site) Lyase*
  • DNA-Binding Proteins / genetics
  • Drosophila Proteins*
  • Gene Expression
  • Glutathione / metabolism*
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Glutathione Transferase / metabolism
  • Kidney / metabolism
  • Male
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred F344
  • Thioredoxins / metabolism*
  • Transcription Factors*
  • Translocation, Genetic


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Transcription Factors
  • Trl protein, Drosophila
  • Thioredoxins
  • Glutathione Peroxidase
  • Glutathione Reductase
  • Glutathione Transferase
  • Carbon-Oxygen Lyases
  • Apex1 protein, rat
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Glutathione