John C. Newman and Eric Verdin
Traditionally, the ketone body b-hydroxybutyrate (bOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, bOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which bOHB functions to link the environment, in this case the diet, and gene expression via chromatin modifications. We review the regulation and functions of ketone bodies, the relationship between ketone bodies and calorie restriction, and the implications of HDAC inhibition by the ketone body bOHB in the modulation of metabolism and in diseases of aging.