Effect of age and caloric restriction on bleomycin-chelatable and nonheme iron in different tissues of C57BL/6 mice

The objective of this study was to test the hypothesis that the widely obse rved age-associated increase in the amounts of macromolecular oxidative dam age is due to an elevation in the availability of redox-active iron, that i s believed to catalyze the scission of H2O2 to generate the highly reactive hydroxyl radical. Concentrations of bleomycin-chelatable iron and nonheme iron were measured in various tissues and different regions of the brain of mice fed on ad libitum (AL) or a calorically restricted (to 60% of AL) die t at different ages. The concentrations of these two pools of iron varied m arkedly as a function of tissue, age, and caloric intake. There was no cons istent ratio between the amounts of nonheme and the bleomycin-chelatable ir on pools across these conditions. Nonheme iron concentration increased with age in the liver, kidney, heart, striatum, hippocampus, midbrain and cereb ellum of AL animals, whereas bleomycin-chelatable iron increased significan tly with age only in the liver. Amounts of both nonheme and bleomycin-chela table iron remained unaltered during aging in the cerebral cortex and hindb rain of AL mice. Caloric restriction had no effect on iron concentration in the brain or heart, but caused a marked increase in the concentration of b oth bleomycin-chelatable and nonheme iron in the liver and the kidney. The results do not support the hypothesis that accumulation of oxidative damage with age, or its attenuation by CR, are associated with corresponding vari ations in redox-active iron. (C) 1999 Elsevier Science Inc.