Cellular signaling, AGE accumulation and gene expression in hepatocytes of lean aging rats fed ad libitum or food-restricted.

The effects of food restriction on liver glucagon and vasopressin V1a receptors, on AGE accumulation and on gene expression were investigated in 10- and 30-month-old WAG/Rij female rats fed ad libitum or chronically food-restricted by 30%. The age-related increase in glucagon and vasopressin V1a receptor density, as well as the rise in glucagon-induced cAMP generation was prevented by the restriction. AGE accumulation, characteristic of the aging process, was normalized in food-restricted animals. Gene expression determined with rat Atlas cDNA Expression Arrays containing 1176 cDNA indicates that a few genes exhibited a greater than twofold change in mRNA ratios with age. Most down-regulated genes were related to oxidative metabolism of lipids, and most of the up-regulated genes were concerned with the cell cycle and transcription factors. Chronic food restriction partially prevents these changes in gene expression and induces up- and down-regulation of several mRNAs which are not modified with age in ad libitum fed rats.