Caloric restriction extends lifespan and delays aging in diverse species. On pp. 677–688 of the current issue of Cell Metabolism, Rhoads et al. integrated large-scale data from the hepatic transcriptome, proteome, and metabolome of rhesus monkeys after 2 years on a 30% calorie-restricted diet to reveal multi-modal mechanisms driven by calorie restriction to rewire metabolism. The panels of the cover image represent the four distinct regulatory strategies recruited by caloric restriction: transcriptional, post-transcriptional, translational, and post-translational, each of which gives a different “view” of the unified and integrated molecular response to caloric restriction.