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A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
Published on: September 17, 2020
A High-Throughput Screen for Yeast Replicative Lifespan Identifies Lifespan-Extending Compounds.
Ethan A Sarnoski1, Ping Liu1, Murat Acar2
1Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, CT 06511, USA; Systems Biology Institute, Yale University, 850 West Campus Drive, West Haven, CT 06516, USA.
Researchers developed High-Life, a high-throughput method for measuring yeast replicative lifespan, enabling over 1,000 conditions daily. This technique identified two compounds, terreic and mycophenolic acids, that extend lifespan, aiding pro-longevity drug discovery.
Area of Science:
- Gerontology
- Molecular Biology
- Biotechnology
Background:
- Aging research is significantly limited by the time-consuming nature of lifespan measurements.
- Current methods for yeast replicative lifespan, a rapid model for aging, allow only a few measurements per day.
- High-throughput screening is crucial for accelerating the discovery of interventions that promote longevity.
Purpose of the Study:
- To develop a novel, high-throughput technique for measuring replicative lifespan in Saccharomyces cerevisiae.
- To validate the new technique using known lifespan-modulating factors.
- To utilize the technique for screening compounds that extend lifespan.
Main Methods:
- A 384-well plate-based method, termed High-Life, was developed for yeast replicative lifespan measurement.
- The technique was validated using long-lived mutant strains and the lifespan-extending drug ibuprofen.
- A small compound library was screened for lifespan-extending properties using the High-Life technique.
Main Results:
- The High-Life technique enables a single researcher to assess over 1,000 lifespan conditions per day.
- Validation confirmed the technique's accuracy with known lifespan modifiers.
- Screening identified terreic acid and mycophenolic acid as compounds extending mean replicative lifespan by 15% and 20%, respectively.
Conclusions:
- High-Life provides a significant advancement in the speed and scale of replicative lifespan measurement.
- The identified compounds, terreic acid and mycophenolic acid, show potential as pro-longevity agents.
- This high-throughput approach can accelerate the discovery of novel therapeutics for age-related conditions.

