Gene expression by myriocin treatment

Studies of aging and longevity are revealing how diseases that shorten life can be controlled to improve the quality of life and lifespan itself. Two strategies under intense study to accomplish this goal are rapamycin treatment and calorie restriction. New strategies are being discovered including one that uses low-dose myriocin treatment. Myriocin inhibits the first enzyme in sphingolipid synthesis in all eukaryotes and we showed recently that low-dose myriocin treatment increases yeast lifespan at least in part by down-regulating the sphingolipid-controlled Pkh1/2-Sch9 (ortholog of mammalian S6 kinase) signaling pathway. Here we show that myriocin treatment has global influences and modulates the evolutionarily conserved Snf1/AMPK, PKA and TORC1 signaling pathways to enhance yeast lifespan. These extensive affects of myriocin rival those of rapamycin and calorie restriction. Our studies in yeast along with other studies in mammals reveal the potential of myriocin or related compounds to lower the incidence of age-related diseases in humans. No-myriocin-treated cells and myriocin-treated cells; three biological replicates in each treatment