| Aging is a complex and irreversible physiological process,its manifestation mainly includes:biological function declining with time,reduced resistance to varions stresses,and increased susceptibility to various diseases.Studies have shown that genomic stability,telomere loss,epigenetics,protein homeostasis,mitochondrial status,nutrition sensing,cell-cell communication,stem cell renewal,and tissue regeneration ability are closely related to aging.One of primary objectives about researching on aging is to develop interventions and means（such as caloric restriction and the first drug intervention used in clinical trials-metformin,etc.）,thereby to delay the arises of aging-related diseases and to extend the individual’s healthy lifespan.Accordingly,it’s crucial to elucidate the molecular mechanisms of aging,thereby finding the appropriate anti-aging drugs and its target.Myriocin,C12H39NO6,is a metabolite of the entomopathogenic fungus-Cordyceps sinensis,also known as ISP-1,which potently and selectively inhibits the activity of the first step rate-responsive enzyme,serine palmitase（SPT）,in the synthesis of sphingolipids,thereby reducing the biosynthesis of sphingolipid precursor sphingosine.Studies have shown that myriocin may be a potentially important targeted drug for the treatment of cardiovascular diseases such as atherosclerosis.Animal models based on obesity and type I and type II diabetes have shown that myriocin treatment inhibits de novo synthesis of ceramides can improve glucose homeostasis and systemic insulin response in the model.Our prophase study showed that myriocin can significantly prolong lifespan of Saccharomyces cerevisiae through signaling pathways related to aging and longevity（reducing the activity of TORC1 and PKA and activating Snf1）and prolong lifespan of fission Saccharomyces cerevisiae by relying on the stress-responsive protein kinase Sty1.In order to further elucidate the mechanism of prolonging lifespan of Saccharomyces cerevisiae cells by myriocin,based on prophase studies,effects of myriocin on the transcriptome of Saccharomyces cerevisiae cells were analyzed by means of bioinformatics（Principal component analysis,Heatmap analysis,Different gene expression analysis,GO Terms and Signaling Pathways）and performed functional validation experiments on some of the significant differences in the results of the bioinformatics analysis.The main bioinformatics analysis showed that myriocin had significant effects on mitochondria-related functions,actin dynamics and peroxisomal function.And through ROS levels,mitochondrial membrane potential,mitochondrial respiratory chain related protein expression,actin dynamics and the number of peroxisomes,we found that myriocin can regulate mitochondrial respiratory function,enhance actin dynamics and increase the number of peroxidase.This study provides the basis and clues in clarifying the anti-aging mechanism of myriocin and provides a theoretical basis for the next step in the development and application of myriocin to delay aging and control the occurrence and development of age-related diseases. |
