PMID- 12957655 OWN - NLM STAT- MEDLINE DCOM- 20040512 LR - 20190827 IS - 0891-5849 (Print) IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 35 IP - 6 DP - 2003 Sep 15 TI - Effects of age and caloric restriction on glutathione redox state in mice. PG - 626-35 AB - 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. FAU - Rebrin, Igor AU - Rebrin I AD - Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles, CA 90033, USA. FAU - Kamzalov, Sergey AU - Kamzalov S FAU - Sohal, Rajindar S AU - Sohal RS LA - eng GR - R01 AG013563/AG/NIA NIH HHS/United States GR - R01 AG013563-13/AG/NIA NIH HHS/United States GR - R01 AG13563/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - GAN16C9B8O (Glutathione) RN - ULW86O013H (Glutathione Disulfide) SB - IM MH - Aging/*physiology MH - Animals MH - Brain/metabolism MH - *Caloric Restriction MH - Eye/metabolism MH - Glutathione/*metabolism MH - Glutathione Disulfide/metabolism MH - Kidney/metabolism MH - Liver/metabolism MH - Male MH - Mice MH - Mitochondria/metabolism MH - Myocardium/metabolism MH - Oxidation-Reduction MH - Testis/metabolism PMC - PMC2837076 MID - NIHMS182388 EDAT- 2003/09/06 05:00 MHDA- 2004/05/13 05:00 PMCR- 2010/03/11 CRDT- 2003/09/06 05:00 PHST- 2003/09/06 05:00 [pubmed] PHST- 2004/05/13 05:00 [medline] PHST- 2003/09/06 05:00 [entrez] PHST- 2010/03/11 00:00 [pmc-release] AID - S0891584903003885 [pii] AID - 10.1016/s0891-5849(03)00388-5 [doi] PST - ppublish SO - Free Radic Biol Med. 2003 Sep 15;35(6):626-35. doi: 10.1016/s0891-5849(03)00388-5.