Recent progress in the biology and physiology of sirtuins

Since the discovery that the life extending benefits of caloric restriction in yeast require Sir2, a protein originally isolated in a screen for gene silencing factors (and called silent information regulator 2), there has been considerable interest in the family of proteins collectively known as the sirtuins. This week Toren Finkel, Chu-Xia Deng and Raul Mostoslavsky review recent advances in sirtuin biology. These NAD-dependent enzymes have been implicated in a wide array of cell-fate decisions, in maintaining genomic stability and regulating overall energy metabolism. Increasing evidence also implicates the sirtuins in the progression of a number of disease states ranging from diabetes to cancer. These observations, coupled with the recent progress in the rationale design of small molecule sirtuin activators, raise the possibility of new therapies targeted to a host of age-related diseases, as well as potential pharmacological strategies to slow mammalian ageing.