| Aging is the gradual loss of the ability of organisms to maintain molecular,cellular or individual levels of physiological integrity, manifested as a biological process in which the resistance of cells or organisms to various stresses and diseases is gradually declining. Aging occurs in almost every species, and humans are no exception. Human aging is concentrated in the body of aging-related diseases(including cardiovascular disease, type 2 diabetes, neurodegenerative diseases and cancer, etc.) resistance decreased and mortality increased. In recent years, studies have shown that aging itself is the most risk factor of aging-related diseases, and found that the development of aging and aging-related diseases have a common molecular regulation mechanism. Aging is a complex phenotype controlled by multiple factors. In recent years, studies suggest that aging can be regulated (such as genetic interference, nutritional interventions and drug treatment, etc.). Among them,the research and development of anti-aging active molecules/drugs is becoming a hot topic in the field of aging and aging related diseases because of its theoretical feasibility and practical application. Screening high effective, low side effect and broad spectrum anti-aging active molecules from natural products is the main strategy for anti-aging and aging-related diseases.Previous studies have found that the natural product of myriocin, a specific inhibitor of sphingolipid synthesis, can prolong the lifespan of the model organisms in budding yeast Saccharomyces cerevisiae, while the fission yeast Schizosaccharomyce pombe is an 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 Schizosaccharomyce pombe was investigated in this study, and its mechanism of lifespan regulation was further studied.In this study, we examined the effects of different concentrations of myriocin on the growth of wild type fission yeast cells, and we found that that myriocin could inhibit cell growth in a dose-dependent manner. The effects of myriocin on lifespan of fission yeast were examined by three methods(Clone counting method, Spot analysis,fluorescence staining method),show that myriocin treatment prolong the lifespan of fission yeast cells in a dose-dependent manner. By detecting the effect of myriocin on the cell processes of fission yeast, it was found that myriocin treatment significantly enhanced heat resistance, oxidation resistance, the acid stress resistance, the salt ion resistance and resistance of heavy metal ions, significantly reduced intracellular reactive oxygen species (ROS) levels, increased intracellular glycogen and trehalose contentIn this study, we investigated the effects of Sty1? ,Pyp1? and wild-type strain on lifespan and thermocompression resistance in the presence or absence of myriocin,found that myriocin can prolong lifespan and enhance heat resistance of WT and Pyp1? ,but could not prolong the Sty1? lifespan and heat resistance, the results show that Styl play an important role in myriocin-mediated lifespan extension.Furthermore, the expression of Sty1 protein and the phosphorylation of Sty1 protein in WT yeast cells were further detected, found that myriocin could increase the expression of Sty1, can not increase the phosphorylation of Styl protein, showed that myriocin-mediated lifespan extension depends on Styl (mainly by enhancing Styl protein expression, but does not depend on Pypl and its mediated phosphorylation of Pyp1-Styl).In summary. The results show that myriocin conservatively prolonged the life of fission yeast Schizosaccharomyce pombe, and its mechanism of lifespan extension includes enhanced cell stress resistance, promoted the accumulation of glycogen and trehalose, reduced intracellular reactive oxygen species, and further studies showed that myriocin-mediated lifespan extension depends on the stress-responsive protein kinase Sty1. Overall, the results suggest that myriocin is a potential anti-aging drug molecule, the latter is expected to develop it for the delay of mammalian cells(including humans) aging and prevention and treatment of aging-related diseases. |
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