title: Effects of age and caloric restriction on glutathione redox state in mice.
abstract: 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.
authors.affiliation: Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA 90033, USA.
authors.forename: Igor
authors.initials: I
authors.lastname: Rebrin
authors.forename: Sergey
authors.initials: S
authors.lastname: Kamzalov
authors.forename: Rajindar S
authors.initials: RS
authors.lastname: Sohal
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D031204:Caloric Restriction; D005123:Eye / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D019803:Glutathione Disulfide / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D013737:Testis / Q000378:metabolism
chemical_list: D005978:Glutathione; D019803:Glutathione Disulfide