Members of the Klotho gene family have been identified as modulators of the aging process. Deletion of αklotho in the mouse results in a syndrome resembling rapid human aging. Conversely, overexpression of αklotho extends mammalian lifespan. Here, we identify klotho orthologs in the vertebrate aging model Nothobranchius furzeri and provide a detailed spatio-temporal expression profile of both paralogs, α and βklotho, from embryogenesis until old age spanning the entire life cycle of the organism. Specifically, we observe low levels of expression of both paralogs during embryogenesis followed by a significant transcriptional induction as development proceeds. In adult killifish, αklotho is predominantly expressed in the liver, the kidney, and the developing pharyngeal teeth. Particularly high levels of αKlotho protein were identified in the kidney tubules, closely resembling mammalian expression patterns. Prominent βklotho expression was detected in the killifish intestine and liver. Overall, qRT-PCR analysis of Klotho members as a function of age revealed steady transcript levels, except for βklotho expression in the liver which was significantly downregulated with age. This spatio-temporal expression profiling may serve as a useful starting point to further investigate the distinct physiological roles of Klotho members during the aging process.

中文翻译：

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短寿命非洲鳉鱼 Nothobranchius furzeri 中 Klotho 基因家族的系统发育分析和表达谱。

Klotho 基因家族的成员已被确定为衰老过程的调节剂。小鼠中αklotho的缺失会导致类似于人类快速衰老的综合征。相反，αklotho的过度表达会延长哺乳动物的寿命。在这里，我们确定了脊椎动物衰老模型Nothobranchius furzeri中的klotho直系同源物，并提供了从胚胎发生到老年跨越生物体整个生命周期的详细时空表达谱，即α和βklotho的旁系同源物。具体来说，我们观察到胚胎发生过程中两个旁系同源物的低水平表达，随后随着发育的进行显着的转录诱导。在成年鳉鱼中，αklotho主要在肝脏、肾脏和发育中的咽齿中表达。在肾小管中发现了特别高水平的α Klotho 蛋白，与哺乳动物的表达模式非常相似。在鳉鱼肠道和肝脏中检测到显着的βklotho表达。总体而言，作为年龄函数的 Klotho 成员的 qRT-PCR 分析显示稳定的转录水平，除了肝脏中的βklotho表达随年龄显着下调。这种时空表达谱可以作为一个有用的起点，以进一步研究 Klotho 成员在衰老过程中的不同生理作用。