Starvation response in mouse liver shows strong correlation with life-span-prolonging processes

We have monitored global changes in gene expression in mouse liver in response to fasting and sugar- fed conditions using high- density microarrays. From similar to 20,000 different genes, the significantly regulated ones were grouped into specific signaling and metabolic pathways. Striking changes in lipid signaling cascade, insulin and dehydroepiandrosterone ( DHEA) hormonal pathways, urea cycle and S- adenosylmethionine- based methyl transfer systems, and cell apoptosis regulators were observed. Since these pathways have been implicated to play a role in the aging process, and since we observe significant overlap of genes regulated upon starvation with those regulated upon caloric restriction, our analysis suggests that starvation may elicit a stress response that is also elicited during caloric restriction. Therefore, many of the signaling and metabolic components regulated during fasting may be the same as those which mediate caloric restriction- dependent life- span extension.