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A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe
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A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe

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Drug synergy drives conserved pathways to increase fission yeast lifespan

Xinhe Huang1, Markos Leggas2, Robert C Dickson3

  • 1Department of Molecular and Cellular Biochemistry and the Lucille Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky, United States of America. nc.ude.utjws.emoh@gnauhehnix.

Plos One
|March 19, 2015
PubMed

Insights

Combining rapamycin and myriocin extends lifespan in yeast by regulating conserved nutrient and stress pathways. This drug combination may enhance survival and longevity in other species by fine-tuning cellular processes.

Area of Science:

  • Gerontology
  • Molecular Biology
  • Yeast Genetics

Background:

  • Aging is characterized by progressive physiological decline and increased susceptibility to age-related diseases.
  • Strategies to slow aging and extend healthspan are critical for public health.
  • Previous studies showed rapamycin and myriocin synergistically increase lifespan in Saccharomyces cerevisiae.

Purpose of the Study:

  • To investigate the effects of rapamycin and myriocin combination on lifespan in Schizosaccharomyces pombe.
  • To identify conserved signaling pathways regulated by this drug combination.
  • To explore the potential of this combination for promoting longevity across species.

Main Methods:

  • Lifespan analysis in Schizosaccharomyces pombe treated with rapamycin and myriocin.
  • Investigation of conserved signaling pathways including TORC1, PKA, and stress response pathways (Sty1/p38 MAP kinase).

Main Results:

  • The combination of rapamycin and myriocin synergistically increased lifespan in Schizosaccharomyces pombe.
  • This lifespan extension was associated with the regulation of conserved signaling pathways.
  • Key pathways modulated include the target of rapamycin complex 1 (TORC1), protein kinase A (PKA), and the Sty1 stress response pathway.

Conclusions:

  • The rapamycin and myriocin combination extends lifespan in fission yeast by modulating conserved nutrient and stress signaling pathways.
  • These findings suggest that targeting conserved pathways with this drug combination could be a strategy for enhancing longevity.
  • The conserved nature of these pathways indicates potential applicability to other organisms, including mammals.

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