Correlated resistance to glucose deprivation and cytotoxic agents in fibroblast cell lines from long-lived pituitary dwarf mice

Fibroblast cell lines derived from the skin of young adult mice of the long-lived Snell dwarf mutant mouse stock have been shown to be resistant to the cytotoxic effects of multiple agents, including hydrogen peroxide, cadmium, heat, ultraviolet light, and the carcinogen methyl methanesulfonate. Snell dwarf fibroblasts are here reported to differ from control cell lines in two other respects: they are relatively resistant to the metabolic inhibition induced by low glucose concentrations, and also resistant to the effects of the mitochondrial poison rotenone, a blocker of Complex I of the electron transport chain. Furthermore, analysis of cell lines derived from a group of genetically heterogeneous mice established that cell lines resistant to peroxide-induced cytotoxicity were also relatively resistant to death induced by paraquat, cadmium, and ultraviolet light. Resistance to the metabolic effects of low glucose medium was associated with resistance to peroxide and cadmium in cells from heterogeneous mice and Snell dwarf mice, though unexpectedly not associated with resistance to the lethal effects of paraquat or UV light. Further analysis of the basis for metabolic abnormalities in these cell lines may provide insights into the cause of stress resistance in dwarf-derived cultures and to the longevity and disease-resistance of these long-lived mutant mice. (c) 2006 Elsevier Ireland Ltd. All rights reserved.