The present invention provides methods for identifying agents that modulate a level or an activity of a mitochondrial NAD-dependent deacetylase polypeptide, as well as agents identified by the methods. The invention further provides methods of modulating mitochondrial NAD-dependent deacetylase activity in a cell. The invention further provides methods of modulating mitochondrial function by modulating the activity of mitochondrial NAD-dependent deacetylase.