Early hypothalamic response to age-dependent gene expression by calorie restriction

Molecular events linking the initial detection of calorie restriction (CR) to changes in gene expression throughout the organism that ultimately retard aging in CR animals are unknown. This study measured changes in gene expression induced by CR and by aging in the hypothalamus, which likely plays a central role in the initial perception of and response to CR. Hypothalamic expression profiling was done in young (4–6 months) ad libitum fed (AL), young CR (2.5–4.5 months of CR), and old (26–28 months) AL male C57BL/6 mice. CR altered the expression of 137 genes and aging altered 1222. Only 8 age-related genes were oppositely regulated by CR. To test whether reduced plasma glucose is a signal in altering hypothalamic gene expression, we examined GLUT4 transgenic mice (C57BL/6 background; 4–6 months), which have reduced plasma glucose similar to that of CR mice. Twenty-seven genes differed between transgenic and non-transgenic mice; nine of these were only altered by CR. The decreased plasma glucose had a limited role in CR mediated hypothalamic gene expression.