Provided herein are compositions and methods for treating or preventing cancer and autoimmune diseases. Compositions comprise a sirtuin inhibitory compound that decreases the activity of a sirtuin, such as SIRT1 or Sir2. Exemplary methods comprise contacting a cell or a molecule with a sirtuin inhibitory compound that decreases the activity of a sirtuin and thereby reduces the life span of a cell, kills the cell or renders it susceptible to certain cell stresses including radiation and chemotherapy. Other methods include treating pathogens expressing a sirtuin.