A high throughput screening assay was developed based on the yeast chronological aging model and applied in evaluating several factors that mediate lifespan, including inoculum size, cellular state in nutrient-rich medium, and calorie level. Using our assay, we confirmed the previously reported genetic mimics of calorie restriction, including deletion of TOR1, SCH9 or RAS2. In contrast, deletion of SIR2 had longevity effect but seemed to produce only small beneficial effect on the response to calorie restriction. Overall, this new high throughput screening assay may facilitate identification of calorie restriction mimetics with a rapid and simple protocol, uncomplicated data analysis, and high sensitivity. In addition, the assay also provides quantifiable data including lag-time, growth rate, doubling time, and survival percentage.
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