Ketone bodies mimic the life span extending properties of caloric restriction

This paper proposes the hypothesis that the life span extension produced by caloric restriction can be duplicated by the metabolic changes of ketosis. It describes a pathway in which decreased insulin and insulin-like growth factor signaling allows FOXO proteins to stay in the nucleus and increase transcription of antioxidant enzymes, and states that d-beta-hydroxybutyrate inhibits class I and IIa histone deacetylases that repress FOXO3a transcription. It notes that a dietary ketone ester decreases circulating glucose and insulin, and that adding d-beta-hydroxybutyrate to C. elegans cultures extends life span.