Effects of age and caloric restriction on glutathione redox state in mice

• Published in: Free radical biology & medicine Vol. 35; no. 6; pp. 626 - 635
• Main Authors: Rebrin, Igor, Kamzalov, Sergey, Sohal, Rajindar S
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2003
• Subjects: Aging; Aging - physiology; Animals; Brain - metabolism; Caloric Restriction; Eye - metabolism; Free radicals; Glutathiolation; Glutathione; Glutathione - metabolism; Glutathione Disulfide - metabolism; Kidney - metabolism; Liver - metabolism; Male; Mice; Mitochondria; Mitochondria - metabolism; Myocardium - metabolism; Oxidation-Reduction; Oxidative stress; Protein-mixed disulfides; Redox potential; S-thiolation; Testis - metabolism; Glutathiolation; Oxidative stress; Mitochondria; Free radicals; Protein-mixed disulfides; S-thiolation; Aging; Redox potential; Glutathione; Caloric restriction
• ISSN: 0891-5849; 1873-4596
• 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 (∼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.