The founding member of the sirtuin family, yeast Sir2, was the first evolutionarily conserved gene to be identified as a regulator of longevity. Sirtuins constitute a protein family of metabolic sensors, translating changes in NAD + levels into adaptive responses, thereby acting as crucial regulators of the network that controls energy homeostasis and as such determines healthspan. In mammals the sirtuin family comprises seven proteins, SIRT1-SIRT7, which vary in tissue specificity, subcellular localization, enzymatic activity and targets. Here, we report the identification and a detailed spatio-temporal expression profile of sirtuin genes in the short-lived fish Nothobranchius furzeri, from embryogenesis to late adulthood, mapping its entire life cycle. Database exploration of the recently published N. furzeri genome revealed eight orthologues corresponding to the seven known mammalian sirtuins, including two copies of the sirt5 gene. Phylogenetic analysis showed high cross species similarity of individual sirtuins in both their overall amino acid sequence and catalytic domain, suggesting a high degree of functional conservation. Moreover, we show that N. furzeri sirtuins exhibit ubiquitous and wide tissue distribution with a unique spatial expression pattern for each individual member of this enzyme family. Specifically, we observed a transcriptional down-regulation of several sirtuin genes with age, most significantly sirt1, sirt5a, sirt6 and sirt7 in a wide range of functionally distinct tissues. Overall, this spatio-temporal expression analysis provides the foundation for future research, both into genetic and pharmacological manipulation of this important group of enzymes in Nothobranchius furzeri, an emerging model organism for aging research.

瑟土因家族的创始成员酵母Sir2，是第一个被鉴定为长寿调节因子的进化保守基因。Sirtuins构成代谢传感器的蛋白质家族，将NAD +水平的变化转化为适应性反应，从而充当控制能量稳态并因此决定健康期的网络的关键调节剂。在哺乳动物中，瑟土因家族包含七个蛋白质，SIRT1-SIRT7，它们在组织特异性，亚细胞定位，酶活性和靶标上均不同。在这里，我们报道了从存活到胚胎发育到成年后期的短命鱼类Nothobranchius furzeri中的sirtuin基因的鉴定和详细的时空表达谱，描绘了其整个生命周期。最近发布的数据库探索弗氏猪笼草基因组揭示了八个直向同源物，对应于七个已知的哺乳动物沉默调节蛋白，包括两个拷贝的sirt5基因。系统发生分析表明，单个sirtuins在其总体氨基酸序列和催化结构域中都具有很高的跨物种相似性，表明高度的功能保守性。此外，我们表明，该酶家族的每个个体都表现出广泛存在的弗氏猪瑟瑟菌（N. furzeri sirtuins），并且具有独特的空间表达模式。具体来说，我们观察到了一些随着年龄增长的sirtuin基因的转录下调，其中最显着的是sirt1，sirt5a，sirt6和sirt7在各种功能上不同的组织中 总的来说，这种时空表达分析为将来研究衰老的新兴模型生物— Nothobranchius furzeri中这一重要酶的遗传和药理处理提供了未来研究的基础。