Ketone bodies as signaling metabolites

•Ketone bodies have signaling functions as well as being a mobile source of cellular energy.•Ketone bodies inhibit histone deacetylases and control gene transcription.•Histone deacetylase function is implicated in the regulation of aging.•Ketone bodies may link environmental cues such as diet to the regulation of aging.

Traditionally, the ketone body β-hydroxybutyrate (βOHB) has been looked upon as a carrier of energy from liver to peripheral tissues during fasting or exercise. However, βOHB also signals via extracellular receptors and acts as an endogenous inhibitor of histone deacetylases (HDACs). These recent findings support a model in which βOHB 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 βOHB in the modulation of metabolism and in diseases of aging.