Chronological lifespan regulation of Saccharomyces cerevisiae by leucine biosynthesis pathway genes via TOR1 and COX2 expression regulation

초록

BackgroundsLeucine is involved in various cellular mechanisms, including protein metabolism, insulin signaling, and longevity control. Nevertheless, the contribution of leucine metabolism genes to longevity have not been thoroughly studied.MethodsSeveral mutants of leucine biosynthesis genes were constructed, and their effect on yeast lifespan and various phenotypes were examined.ResultsSeveral deletion mutants increase yeast lifespan. Among those, LEU2 and leu4 cells exhibit significantly increased lifespan, moderately increased reactive oxygen species (ROS) generation, decreased Tor1p expression, significantly increased expression of a cytochrome c oxidase subunit, and decreased cell death. In these cells, reduced Tor1p seemed to stimulate a slight increase in ROS generation which stimulates Cox2p expression that can prevent cellular damage. Indeed, the rate of cell death of LEU2 and leu4 cells was drastically decreased.ConclusionLEU2 and LEU4 seem critical in determining yeast lifespan by providing a hormetic effect that promotes yeast longevity.

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