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The Ras and Sch9 pathways regulate stress resistance and longevity
1Division of Biogerontology and Department of Biological Sciences, Andrus Gerontology Center, University of Southern California, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA. vlongo@usc.edu
Experimental Gerontology
|July 12, 2003
Summary
Researchers identified two key pathways regulating yeast longevity and stress resistance. Deleting SCH9 or inhibiting the Ras pathway significantly extends lifespan and enhances stress tolerance in yeast.
Area of Science:
- Cellular biology
- Genetics
- Biochemistry
Background:
- Yeast exhibits distinct metabolic phases (high and low) influencing survival.
- Longevity and stress resistance are critical cellular processes influenced by nutrient availability.
Purpose of the Study:
- To identify molecular pathways regulating longevity and stress resistance in yeast.
- To investigate the role of SCH9 and the Ras/Cyr1/PKA pathway in these processes.
Main Methods:
- Genetic manipulation, including gene deletion (SCH9) and pathway inhibition (Ras/Cyr1/PKA).
- Assessment of lifespan extension and stress resistance (oxidative, thermal).
- Analysis of downstream targets like Msn2/Msn4 transcription factors and Sod2 enzyme.
Main Results:
- Deletion of SCH9 triples yeast mean lifespan and enhances stress resistance.
- Decreased Ras/Cyr1/PKA pathway activity extends longevity and stress resistance.
- These effects are mediated by activating transcription factors Msn2/Msn4 and Sod2.
Conclusions:
- Two distinct pathways, involving SCH9 and the Ras pathway, regulate yeast longevity and stress resistance.
- The Ras pathway's negative regulation of longevity may be conserved in higher eukaryotes.