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Senile muscle atrophy has been attributed to an impaired ability of old nerves to transport trophic factors. To evaluate the effect of age on axoplasmic transport, we measured the accumulation of cholinesterase activity above a ligature around sciatic nerves of young (7--8 months), middle-aged (19--20 months), and old (31--32 months) male rats. Protein content and cholinesterase activity per mm of nerve were higher in middle-aged and old than in young nerves. However, accumulation of cholinesterase activity was significantly lower by middle age and was strikingly reduced by old age. This large reduction in axoplasmic transport appeared to result from factors other than axonal loss. A model in which old nerves have an increased number of temporary focal blockages of particle movement in axoplasmic channels is proposed to explain the decreased transport.

Cytochrome P-450 concentrations in rat liver and kidney were differentially altered by pretreatment with phenobarbital (PB), cadmium or fasting. The rats were then challenged with chloroform. The consequent hepatotoxicity was assayed by alanine amino transferase activity (AlaAT); the nephrotoxicity by inhibition of p-aminohippuric acid (PAH) uptake in vitro and both by histopathology. Fasting increased renal and hepatic cytochromes P-450 and chloroform-mediated necrosis in both organs. PB induction increased and cadmium decreased the liver cytochrome P-450 concentrations and the hepatotoxicity mediated by chloroform. PB and cadmium had no effect on renal cytochrome P-450 concentrations or the nephrotoxicity of chloroform. These results strongly suggest that the nephrotoxic metabolite of chloroform is produced within the kidney and the hepatotoxic metabolite in the liver.