Effects of Age and Caloric Restriction on Glutathione Redox State in Mice

Free Radic Biol Med. 2003 Sep 15;35(6):626-35. doi: 10.1016/s0891-5849(03)00388-5.


The main purpose of this study was to determine whether the aging process in the mouse is associated with a pro-oxidizing shift in the redox state of glutathione and whether restriction of caloric intake, which results in the extension of life span, retards such a shift. Amounts of reduced and oxidized forms of glutathione (GSH and GSSG, respectively) and protein-glutathione mixed disulfides (protein-SSG) were measured in homogenates and mitochondria of liver, kidney, heart, brain, eye, and testis of 4, 10, 22, and 26 month old ad libitum-fed (AL) mice and 22 month old mice fed a diet containing 40% fewer calories than the AL group from the age of 4 months. The concentrations of GSH, GSSG, and protein-SSG vary greatly (approximately 10-, 30-, and 9-fold, respectively) from one tissue to another. During aging, the ratios of GSH:GSSG in mitochondria and tissue homogenates decreased, primarily due to elevations in GSSG content, while the protein-SSG content increased significantly. Glutathione redox potential in mitochondria became less negative, i.e., more pro-oxidizing, as the animal aged. Caloric restriction (CR) lowered the GSSG and protein-SSG content. Results suggest that the aging process in the mouse is associated with a gradual pro-oxidizing shift in the glutathione redox state and that CR attenuates this shift.

Publication types

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

MeSH terms

  • Aging / physiology*
  • Animals
  • Brain / metabolism
  • Caloric Restriction*
  • Eye / metabolism
  • Glutathione / metabolism*
  • Glutathione Disulfide / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Male
  • Mice
  • Mitochondria / metabolism
  • Myocardium / metabolism
  • Oxidation-Reduction
  • Testis / metabolism


  • Glutathione
  • Glutathione Disulfide