Lombard D B, Schwer B, Alt F W, Mostoslavsky R
Howard Hughes Medical Institute, The Children's Hospital, CBR Institute for Biomedical Research, Boston, MA, USA.
J Intern Med. 2008 Feb;263(2):128-41. doi: 10.1111/j.1365-2796.2007.01902.x.
Ageing, or increased mortality with time, coupled with physiologic decline, is a nearly universal yet poorly understood biological phenomenon. Studies in model organisms suggest that two conserved pathways modulate longevity: DNA damage repair and Insulin/Igf1-like signalling. In addition, homologs of yeast Sir2--the sirtuins--regulate lifespan in diverse organisms. Here, we focus on one particular sirtuin, SIRT6. Mice lacking SIRT6 develop a degenerative disorder that in some respects mimics models of accelerated ageing [Cell (2006) 124:315]. We discuss how sirtuins in general and SIRT6 specifically relate to other evolutionarily conserved pathways affecting ageing, and how SIRT6 might function to ensure organismal homeostasis and normal lifespan.
衰老，即随着时间推移死亡率增加并伴有生理机能衰退，是一种几乎普遍存在却又鲜为人知的生物学现象。对模式生物的研究表明，有两条保守途径可调节寿命：DNA损伤修复和胰岛素/胰岛素样生长因子1信号通路。此外，酵母Sir2的同源物——沉默调节蛋白——在多种生物中调节寿命。在此，我们聚焦于一种特定的沉默调节蛋白SIRT6。缺乏SIRT6的小鼠会患上一种退行性疾病，在某些方面类似于加速衰老模型[《细胞》（2006年）第124卷：第315页]。我们将讨论沉默调节蛋白总体上，特别是SIRT6，如何与影响衰老的其他进化保守途径相关，以及SIRT6如何发挥作用以确保机体稳态和正常寿命。
