Fig. P1.

Six cohorts of mice with different energy input and output levels were designed to enable an integrative analysis free of system variations in the data. With this methodology, we investigated whether dietary interventions under the six different conditions target the same set of genes, with expression changes that may modify lifespan. Male mice at 5 wk of age (n = 30/group) maintained on an LF or HF diet were fed ad libitum, subjected to CR (LF + CR or HF + CR; fed daily 70% of the food consumed by the ad libitum group), or permitted voluntary wheel-running exercise (LF + Ex or HF + Ex). At the midlife age of 62 wk, eight mice from each group were killed for analyses of blood and tissues and hepatic gene expression profiling by microarray. The remaining 22 animals in each group were used for lifespan determination.