Association between life-span extension by caloric restriction and thiol redox state in two different strains of mice

• Published in: Free radical biology & medicine Vol. 51; no. 1; pp. 225 - 233
• Main Authors: Rebrin, Igor, Forster, Michael J., Sohal, Rajindar S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2011
• Subjects: Aging; Animals; Caloric Restriction; Dietary restriction; Disulfides - analysis; experimental design; Free radicals; glutamate-cysteine ligase; Glutamate-Cysteine Ligase - metabolism; Glutathione; Glutathione Disulfide - analysis; Glutathione Synthase - analysis; liver; Liver - metabolism; Longevity; low calorie diet; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mixed protein disulfides; Muscle, Skeletal - metabolism; Oxidation-Reduction; Redox state; skeletal muscle; Sulfhydryl Compounds - metabolism; thiols; Aging; Mixed protein disulfides; Redox state; Dietary restriction; Free radicals; Glutathione
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2011.04.006

The hypothesis that the life-extending effect of caloric restriction (CR) is associated with an attenuation of the age-related pro-oxidant shift in the thiol redox state was tested employing a novel experimental design. Amounts of GSH, GSSG, and protein mixed disulfides (Pr-SSG) in the skeletal muscle and liver were compared between two strains of mice that have similar life spans when fed ad libitum (AL), but different life spans under the standard CR regimen. The life span of one strain, C57BL/6, is extended under CR, whereas it remains unaffected in the other strain, DBA/2. Mice were fed AL or 40% less food starting at 4months and compared at 6 and 24months of age. The amounts of GSSG and Pr-SSG increased and the GSH:GSSG ratios decreased with age in both strains of AL-fed mice. CR prevented these age-related changes in the C57BL/6, whose life span is extended by CR, but not in the DBA/2 mice, in which it remains unaffected. CR enhanced the activity of glutamate–cysteine ligase in the C57BL/6, but not in the DBA/2 mice. The results suggest that longevity extension by CR may be associated with the attenuation of age-related pro-oxidizing shifts in the thiol redox state.