There are many pathways and processes that appear to regulate the rate of aging and our susceptibility to age-related diseases such as neurodegeneration, atherosclerosis and cancer. One emerging process that has been increasingly implicated is the activity of the sirtuin family of proteins. Mammals have seven sirtuin family members and they are increasingly seen as a link between againg and metabolism (for review see Finkel et al, Nature, 2009). We have previously made a number of observations regarding the biology of Sirt1 and Sirt3 (see for instance: Nemoto et al., Science 2004;Nemoto et al, JBC, 2005;Lee et al, PNAS 2009;Wang et al., Mol Cell, 2008;Ahn et al., PNAS 2008). Most recently, we have concentrated more on the less well studied sirtuin family members Sirt2 and Sirt6. Ongoing studies have linked Sirt2 to the program of cellular necrosis (Narayan, Nature 2012). We are currently attempting to understand how this regulation is achieved and how it can be potentially manipulated for therapeutic benefit.