We tested the hypothesis that retardation of aging by caloric restriction is due in part to decreased levels of plasma glucose over the life span. Male C57BL/6 mice expressing a human GLUT4 minigene (transgenic [TG] mice) and their nontransgenic littermates (NTG mice) were maintained under specific pathogen-free conditions. Mice were fed ad libitum (A mice) or 40% less than ad libitum (R mice) from age 6 weeks. Over the life span there were three different levels of plasma glucose, with NTGA mice having the highest daily levels, TGR mice the lowest daily values, and TGA and NTGR mice having similar levels intermediate between these values. Despite differences in plasma glucose, the differences measured in longevity (50% and 10% survival), physiology and tissue pathology were associated with diet rather than with levels of plasma glucose. We conclude that decreased plasma glucose over the life span is not an important factor in the action of calorie restriction on aging processes.
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