Calorie restriction extends lifespan in organisms as diverse as yeast and mammals through incompletely understood mechanism(s). The role of NAD+-dependent deacetylases, known as Sirtuins, in this process, particularly in the yeast S. cerevisiae is controversial. We measured chronological lifespan of wild-type and sir2Δ strains over a higher glucose range than typically used for studying yeast calorie restriction. sir2Δ extended lifespan in high-glucose complete minimal medium, and had little effect in low glucose medium, revealing a partial role for Sir2 in the calorie restriction response under these conditions. Experiments performed on cells grown in rich medium with a newly-developed genetic strategy revealed that sir2Δ shortened lifespan in low glucose while having little effect in high glucose, again revealing a partial role for Sir2. In complete minimal media, Sir2 shortened lifespan as glucose levels increased, whereas in rich media, Sir2 extended lifespan as glucose levels decreased. Using a genetic strategy to measure the strength of gene silencing at HML, we determined increasing glucose stabilized Sir2-based silencing during growth on complete minimal media. Conversely, increasing glucose destabilized Sir-based silencing during growth on rich media, specifically during late cell divisions. In rich medium, silencing was far less stable in high glucose than in low glucose during stationary phase. Therefore, Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging, possibly through Sir2-dependent modification of chromatin or deacetylation of a non-histone protein.
- Received October 4, 2016.
- Accepted December 22, 2016.
- Copyright © 2017, The Genetics Society of America