多球壳菌素延长裂殖酵母细胞寿命可能机制研究

Possible Mechanism for Myriocin-mediated Chronological Lifespan Extension in Fission Yeast Schizosaccharomyce pombe

寻找抗衰老活性分子并研究其作用机制是衰老药物学的研究重点和热点。前期研究发现天然产物多球壳菌素(一种神经鞘脂合成特异性抑制剂)能够延长模式生物芽殖酵母的寿命,而裂殖酵母在进化上更接近哺乳动物,且在形态和遗传上与芽殖酵母有显著差异的另一种模式生物,本研究考察了多球壳菌素对裂殖酵母寿命的影响,并进一步研究了其调控细胞寿命的相关机制。结果显示,多球壳菌素延长裂殖酵母寿命具有保守性,其延长细胞寿命的机制包括:增强细胞压力抗性、促进糖原和海藻糖的积累、降低胞内活性氧的水平,且发现多球壳菌素介导的寿命延长依赖于压力应答类蛋白激酶Sty1。综上,多球壳菌素是一种潜在的抗衰老药物分子,后期有望开发它用于延缓哺乳动物细胞(包括人类)衰老及预防和治疗衰老相关疾病。

Looking for anti-aging compounds and studying its action mechanismare the focus and hotspot of aging phar- macology. Previous studies had found that the natural product of myriocin （ a sphingolipid synthesis inhibitor） can pro- long the lifespan of model organism budding yeast Saccharomyces cerevisiae, while the fission yeast Schizosaccharomyce- pombe is another modelorganism evolutionarily closer to the mammals, and is significantly different from the budding yeast in morphology and genetics. The effect of myriocin on the lifespan of fission yeast S. pombe was investigated in this study, and the mechanism of myrioin-mediated lifespan regulation was further studied. The results showed that myriocin conservatively prolonged lifespan of fission yeast S. pombe, and mechanisms for myrioin-mediated lifespan extension in- cluded enhancing cell stress resistance, accumulation of glycogen and trehalose, reducing intracellular reactive oxygen species. Further studies showed that myriocin-mediated lifespan extension depends on the stress-responsive protein ki- nase Styl. In summary, myriocin is a potential anti-aging drug molecule, in future it is expected to be developed into a new drug for the delay of mammalian cells （ including humans） aging and prevention and treatment of aging-related dis- eases.