This proposal requests support for a Keystone Symposia meeting entitled Sirtuins in Metabolism, Aging and Disease, organized by Alexsey G. Kazantsev, Antonello Mai and Tiago Fleming Outeiro, which will be held in Tahoe City, California from February 12 - 16, 2012. Sirtuins comprise a unique class of NAD+dependent enzymes that modify multiple protein substrates to execute diverse biological functions. Sirtuins are key regulators of clinically important cellular and organismal processes including metabolism, cell division and aging. The desire to understand the important determinants of human health and lifespan has resulted in a firestorm of work on the seven mammalian sirtuins in the past decade. The implication of sirtuins in medically important areas such as diabetes, cancer, cardiovascular dysfunction and neurodegenerative disease has catapulted them to a prominent status as potential targets for nutritional and therapeutic development. The Keystone Symposia meeting on Sirtuins in Metabolism, Aging and Disease will address fundamental questions on the regulation, biochemical, molecular and cellular mechanisms and pathways of sirtuins. The significance of sirtuin-dependent regulation of homeostasis with respect to diverse biological organisms will be discussed. We envision that this meeting will evaluate the relevance of sirtuin biology in various human conditions, and provide a unique environment for discussing specific therapeutic strategies. PUBLIC HEALTH RELEVANCE: Sirtuins are a unique class of enzymes in animals that were originally discovered because of their role in the aging process;subsequent research implicates sirtuins in a wide variety of biological functions, including metabolism and development. The Keystone Symposia meeting on Sirtuins in Metabolism, Aging and Disease will critically examine sirtuin biological and therapeutic roles, and aims to formalize sirtuin research as an independent scientific field of high significance.