Drug synergy drives conserved pathways to increase fission yeast lifespan

PloS One
Xinhe HuangRobert C Dickson

Abstract

Aging occurs over time with gradual and progressive loss of physiological function. Strategies to reduce the rate of functional loss and mitigate the subsequent onset of deadly age-related diseases are being sought. We demonstrated previously that a combination of rapamycin and myriocin reduces age-related functional loss in the Baker's yeast Saccharomyces cerevisiae and produces a synergistic increase in lifespan. Here we show that the same drug combination also produces a synergistic increase in the lifespan of the fission yeast Schizosaccharomyces pombe and does so by controlling signal transduction pathways conserved across a wide evolutionary time span ranging from yeasts to mammals. Pathways include the target of rapamycin complex 1 (TORC1) protein kinase, the protein kinase A (PKA) and a stress response pathway, which in fission yeasts contains the Sty1 protein kinase, an ortholog of the mammalian p38 MAP kinase, a type of Stress Activated Protein Kinase (SAPK). These results along with previous studies in S. cerevisiae support the premise that the combination of rapamycin and myriocin enhances lifespan by regulating signaling pathways that couple nutrient and environmental conditions to cellular processes that fine-tune...Continue Reading

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Citations

May 13, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hokuto OhtsukaHirofumi Aiba
Sep 18, 2021·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kotaro MatsuiHirofumi Aiba

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Methods Mentioned

BETA
environmental stresses
GTPase
protein assay

Software Mentioned

ComboDT
Image Lab

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