The biology of the sirtuins

有许多途径和过程似乎可以调节衰老的速度和我们对年龄相关疾病的易感性，如神经变性，动脉粥样硬化和癌症。一个新兴的过程，已越来越多地牵连是活性的sirtuin家族的蛋白质。哺乳动物具有七个去乙酰化酶家族成员，并且它们越来越多地被视为衰老和代谢之间的联系（综述参见Finkel等人，Nature，2009）。 我们先前已经对Sirt 1和Sirt 3的生物学进行了许多观察（参见例如：Nemoto等人，Science 2004; Nemoto等人，JBC，2005; Lee等人，PNAS 2009; Wang等人，Mol Cell，2008; Ahn等人，PNAS 2008）。最近，我们更多地关注研究较少的sirtuin家族成员Sirt 2和Sirt 6。正在进行的研究将Sirt 2与细胞坏死程序联系起来（Narayan，提交）。我们目前正试图了解这种调节是如何实现的，以及如何潜在地操纵它以获得治疗益处。

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, submitted). We are currently attempting to understand how this regulation is achieved and how it can be potentially manipulated for therapeutic benefit.