Oxidative status in senescence-accelerated mice.

The lipid peroxidation and activities of antioxidant enzymes were examined in the livers of two substrains of senescence-accelerated mice (SAM): senescence-resistant SAM-R/1 and senescence-prone SAM-P/1. Fluorescent age pigment and conjugated diene levels in both substrains increased gradually with age, but we found higher levels in SAM-P/1 at all ages tested. Differences in the levels of lipid peroxidation products became more marked with age. Among the enzymes studied, only mitochondrial superoxide dismutase (SOD) in SAM-P/1 showed decreased activity in all age groups. The specific mitochondrial SOD in that case was Cu,Zn-SOD. The amount of Cu,Zn-SOD in mitochondrial fractions of SAM-P/1 was only half that of SAM-R/1, whereas there were no apparent differences in the mRNA levels of both SAM groups. Our study indicates that impaired transport of Cu,Zn-SOD into mitochondria after cytosolic synthesis reduces defense against oxidative stress. That reduction may be one of the factors contributing to accelerated senescence in the SAM-P/1.