Teasing Apart Facets of Calorie Restriction

This paper shows researchers beginning to be able to distinguish between the genetic machinery that causes different parts of the calorie restriction effect on health and longevity: "The FoxO transcription factors may be involved in the antiaging effect of calorie restriction (CR) in mammals. To test the hypothesis, we used FoxO1-knockout heterozygotic (HT) mice, in which the FoxO1 mRNA level was reduced by 50%, or less, of that in wild-type (WT) mouse tissues. The WT and HT mice were fed ad libitum (AL) or 30% CR diets from 12 weeks of age. Aging- and CR-related changes in body weight, food intake, blood glucose and insulin concentrations were similar between the WT and HT mice in the lifespan study. ... Several of the selected FoxO1-target genes for cell cycle arrest, DNA repair, apoptosis, and stress resistance, were up-regulated in the WT-CR tissues, [while] the effect was mostly diminished in the HT-CR tissues. Of these gene products, we focused on the nuclear p21 protein level in the liver and confirmed its up-regulation only in the WT-CR mice in response to oxidative stress. The lifespan did not differ significantly between the WT and HT mice in AL or CR conditions. However, the [cancer resistance] effect of CR, as indicated by reduced incidence of tumors at death in the WT-CR mice, was mostly abrogated in the HT-CR mice. The present results suggest a role for FoxO1 in the [anti-cancer] effect of CR through the induction of genes responsible for protection against oxidative and genotoxic stress."

Link: http://www.ncbi.nlm.nih.gov/pubmed/20222901

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