Skip to main content
Log in

Effect of calorie restriction on liver and kidney glutathione in aging emory mice

  • Published:
AGE Aims and scope Submit manuscript

Abstract

Increases in antioxidant defense capacity have been associated with increases in the health and life span of calorie restricted animals. Emory mice develop late-life cataract, a lesion associated with oxidative damage and loss of lens glutathione (GSH). The effect of calorie restriction on GSH in liver and kidney in this model has not been explored. GSH and oxidized GSH (GSSG) were measured by HPLC in liver and kidney of Emory mice fed a control diet (C; 85% calories of ad-lib fed mice) or 60% calorie intake of C (R; 40% calorie restriction relative to C mice) for up to 22 mo age. Liver GSH concentration increased significantly in C and R mice from 4.5 to 12 mo old with no difference observed between the two groups. At 22 mo of age, liver GSH was lower than that of 12 mo old in both groups. As compared with GSH at 12 mo old, this decrease was almost twice as greater in C (70%, p=0.001) than in R mice (36%, p=0.02), so that R mice had a significantly higher concentration of GSH in liver than C mice at 22 mo of age (R = 32.8+5.1, C= 22.1+8.3 imol GSH/g protein, p<0.01). Liver GSSG was similar in C and R mice at 12 mo of age (4.45+1.35 vs. 4.75+1.83 imol GSSG/g protein), but increased in R mice at 22 mo (R=5:43±1.48; C=3.22±1.02, p<0.01). Therefore, at 22 mo old, total liver glutathione (GSH+GSSG) was higher in R than in C mice. There was no significant difference in GSH, GSSG and total GSH in kidney from C and R mice at these ages. Thus, calorie restriction reduces the age-related loss of GSH antioxidant capacity in liver but not kidney of Emory mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cheney K. E., Liu R. K., Smith G. S., Meredith P. J., McKey M. R., and Walford R. L., The effect of dietary restriction of varying duration on survival, tumor patterns, immune function, and body temperature in B10C3F1 female mice. J. Gerontol., 38: 420–430, 1983.

    PubMed  CAS  Google Scholar 

  2. Weindruch R., Walford R. L., Fligiel S., and Guthrie D., The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr., 116: 641–654, 1986.

    PubMed  CAS  Google Scholar 

  3. Yu B. P., Laganiere S., and Kim J. W., Influence of life-prolonging food restriction on membrane lipoperoxidation and antioxidant status, in Oxygen Radicals in Biology and Medicine, Basic Life Science, Simic MG, et al., Editor.; Plenum Press: New York. p. 1067–1073, 1988.

    Google Scholar 

  4. Laganiere S. A., and Yu B. P., Effect of chronic food restriction in aging rats. I: Liver subcellular membranes. Mech. Ageing. Dev., 48: 207–219, 1989.

    Article  PubMed  CAS  Google Scholar 

  5. Beutler E., Nutritional and metabolic aspects of glutathione. Annual Rev. Nutr., 9: 287–302, 1989.

    Article  CAS  Google Scholar 

  6. Gibson D., Hawtylko J., and McKay P.B., GSH-dependent inhibition of lipid peroxidation: properties of a potent cytosolic system which protects cell membrane. Lipids, 20:704–711, 1985.

    PubMed  CAS  Google Scholar 

  7. Mannervik B., Glutathione peroxidase. Methods Enzymol., 113: 490–495, 1985.

    PubMed  CAS  Google Scholar 

  8. Meister A., and Anderson M. E., Glutathione. Ann. Rev. Biochem., 52:711–760, 1983.

    Article  PubMed  CAS  Google Scholar 

  9. Taylor A., Jacques P. F., and Dorey C. K., Oxidation and aging: impact on vision., inAntioxidants: Chemical, Physiological, Nutritional and Toxicological Aspects., Williams GM, Editor.; Princeton Publishing Co.: Princeton, NJ. p. 349–371, 1992.

    Google Scholar 

  10. Reed D. J., Regulation of reductive processes by glutathione-Biochem. Pharmacol., 35: 7–13, 1986.

    CAS  Google Scholar 

  11. Larsson A., Orrenius S., Holmgren A., and Mannervik B., Functions of glutathione.; New York: Raven Press. 1983.

    Google Scholar 

  12. Winkler B. S., DeSanti N., and Solomon F., Multiple NADPH-producing pathways control glutathione (GSH) content in retina. Exp, Eye Res., 43: 829–847, 1986.

    CAS  Google Scholar 

  13. Neal R. A., Meatbolism of toxic substances., in Toxicology, the basic science of toxicology., Doull J, Klaassen CD, and Amdur MO, Editor.; MacMillan Publishing Co.: New York. p. 56–83, 1980.

    Google Scholar 

  14. Stoh S. J., and Hassing J. M., Glutathione levels in hepatic and extrahepatic tissues of mice as a function of age. Age, 3:11–15, 1980.

    Google Scholar 

  15. Julius M., Lang C. A., Gleiberman L, Harburg E., DiFranceisco W., and Schork A., Glutathione and morbidity in a community-based sample of elderly. J. Clin. Epi., 47: 1021–1026, 1994.

    Article  CAS  Google Scholar 

  16. Favilli F., Iantomasi T., Marraccini P., Stio M., Lunghi B., Treves C., and Vincenzini M. T., Relationship between age and GSH metabolism in synaptosomes of rat cerebral cortex. Neurobiol. Aging, 15: 429–433, 1994.

    Article  PubMed  CAS  Google Scholar 

  17. Kretzschmar M., and Muller D., Aging, training and exercise. A review of effects on plasma glutathione and lipid peroxides. Sports Med., 15: 196–209, 1993.

    Article  PubMed  CAS  Google Scholar 

  18. Lang C. A., Naryshkin S., Schneider D. L., Mills B. J., and Lindeman R. D., Low blood glutathione levels in healthy aging adults. J. Lab. Clin. Med., 120: 720–725, 1992.

    PubMed  CAS  Google Scholar 

  19. Vogt B. L., and Richie J. P. J., Fasting-induced depletion of glutathione in the aging mouse: Biochem. Pharmacol., 46: 257–263, 1993.

    CAS  Google Scholar 

  20. Hazelton G. A., and Lang C. A., Glutathione contents of tissues in the aging mouse. Biochem. J., 188: 25–30, 1979.

    Google Scholar 

  21. Imanishi H., Nakai T., Abe T., and Takino T., Glutathione metabolism in red cell aging. Mech, Ageing Dev., 32: 57–62, 1985.

    Article  CAS  Google Scholar 

  22. Furukawa T., Meydani S. N., and Blumberg J. B., Reversal of age-associated decline in immune responsiveness by dietary glutathione supplementation in mice. Mech. Ageing Dev., 38:107–117, 1987.

    Article  PubMed  CAS  Google Scholar 

  23. Kuck J. F. R., Late onset heredity cataract of the emery mouse, a model for human senile cataract. Exp. Eye Res., 50: 659–664, 1990.

    Article  PubMed  CAS  Google Scholar 

  24. Terameto S., Fukuchi Y., Uejima Y., Ito H., and Orimo H., Age-related changes in GSH content of eyes in mice—a comparison of senescence-accelerated mouse (SAM) and C57BL/J mice. Comp. Biochem. Physiol., 102: 693–696, 1992.

    Article  Google Scholar 

  25. Taylor A., Lipman R. D., Jahngen-Hodge J., Palmer V., Smith D., Padhye N., Dallal G. E., Cyr D. E., Laxman E., Shepard D., Marrow F., Salmon R., Perrone G., Asmundsson G., Meydani M., Blumberg J., Mune M., Harrison D., Archer J. R., and Shigenaga M., Dietary calorie restriction in the Emory mouse: effect on lifespan, eye lens cataract prevalence and progression, level of ascorbate, glutathione, glucose, and glycohemoglubin, tail collagen breaktime, DNA and RNA oxidation, skin integrity, fecundity, and cancer. Mech. Ageing Dev., 79: 33–57, 1995.

    Article  PubMed  CAS  Google Scholar 

  26. Kamei A., Glutathione levels of the human crystalline lens in aging and its antioxidant effect against the oxidation of lens proteins. Biol. Pharmac. Bull., 16: 870–875, 1993.

    CAS  Google Scholar 

  27. Stio M., Iantomasi T., Favilli F., Marraccini P., Lungh i. B., Vincenzini M., and Treves C., Glutathione metabolism in heart and liver of the aging rat. Biochem. Cell Biol., 72: 58–61, 1994.

    Article  PubMed  CAS  Google Scholar 

  28. Taylor A., Zuliani A. M., Hopkins R. E., Dallal G. E., Treglia P., Kuck J. F. R., and Kuck K., Moderate caloric restriction delays cataract formation in the Emory mouse. FASEB J., 3: 1741–1746, 1989.

    PubMed  CAS  Google Scholar 

  29. Mura C. V., Roh D., Smith D., Palmer V., Padyhe N., and Taylor A., Cataract incidence and analysis of lens crystallins in the water-, urea-and SDS-solublefractions of Emory mice fed a diet restricted by 40% in calories. Curr. Eye Res., 12:1081–1092, 1993.

    PubMed  CAS  Google Scholar 

  30. Fariss M. W., and Reed D. J., High performance liquid chromatography of thiols and disulfides: dinitrophenol derivatives. Methods Enzymol., 143: 101–109., 1987.

    Article  PubMed  CAS  Google Scholar 

  31. Brigelius R. M. C., Akerboom T., and Seis H., Identification and quantitation of glutathione in hepatic protein mixed disulfides and its relationship to glutathione disulfide. Biochem. Pharmacol., 32: 2529–2534, 1983.

    Article  PubMed  CAS  Google Scholar 

  32. Lowry O. H., Rosebrough N. J., Farr A. L., and Randall R. J., Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193: 265, 1951.

    PubMed  CAS  Google Scholar 

  33. Gong X., Shang F., Palmer H., Mura C., Scrofano M., Jahngen-Hodge J., Smith D., Khu P., and Taylor A., Effect of dietary calorie restriction and aging on activities of antioxidant enzymes in the lens of Emory mice. Invest. Ophtalmol. Vis. Sci., 36: S525, 1995.

    Google Scholar 

  34. Rao G., Xia E., Nadakavukaren M. J., and Richardson A., Effect of dietary restriction on the age-dependent changes in the expression of antioxidant enzymes in rat liver. J. Nutr., 120: 602–609, 1990.

    PubMed  CAS  Google Scholar 

  35. Taylor A., Jahngen-Hodge J., Smith D. E., Palmer V. J., Dallal G. E., Lipman R. D., Padhye N., and Frei B., Dietary Restriction delays catract and reduces ascorbate levels in Emory mice. Exp. Eye Res.,: (in press), 1995.

  36. Richie J. P. J., Leutzinger Y., Parthasarathy S., Malloy V., and Orentreich N., Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J., 8: 1302–1307, 1994.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Mune, M., Meydani, M., Jahngen-Hodge, J. et al. Effect of calorie restriction on liver and kidney glutathione in aging emory mice. AGE 18, 43–49 (1995). https://doi.org/10.1007/BF02432518

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02432518

Keywords

Navigation