Department of Frontier Bioscience, Nagahama Institute of Bio-Science and Technology, Shiga, Japan.
FEBS Lett. 2020 Apr;594(7):1166-1175. doi: 10.1002/1873-3468.13707. Epub 2019 Dec 16.
Lifespan is determined by genetic factors and influenced by environmental factors. Here, we find that the phosphate signal transduction (PHO) pathway is involved in the determination of replicative lifespan in budding yeast. Extracellular phosphate does not affect the lifespan. However, deletion of PHO80 (cyclin) and PHO85 (cyclin-dependent kinase) genes, that is, negative regulators of the PHO pathway, shortens the lifespan, which is restored by further deletion of PHO4 (transcriptional activator). Four of the other nine Pho85p cyclin genes are also required to maintain normal lifespan. The short-lived mutants show a metabolic profile that is similar to strains with normal lifespan. Thus, Pho85p kinase genetically determines replicative lifespan in combination with relevant cyclins. Our findings uncover novel cellular signals in longevity regulation.
寿命由遗传因素决定，并受环境因素影响。在这里，我们发现磷酸盐信号转导（PHO）途径参与了芽殖酵母复制寿命的决定。细胞外磷酸盐不会影响寿命。然而，删除 PHO80（细胞周期蛋白）和 PHO85（细胞周期蛋白依赖性激酶）基因，即 PHO 途径的负调节剂，会缩短寿命，而过表达 PHO4（转录激活因子）可以恢复寿命。其他九个 Pho85p 细胞周期蛋白基因中的四个也需要维持正常寿命。寿命短的突变体表现出与具有正常寿命的菌株相似的代谢谱。因此，Pho85p 激酶与相关细胞周期蛋白一起在遗传上决定复制寿命。我们的发现揭示了长寿调控中的新细胞信号。
