Sir2 is an NAD+-dependent protein deacetylase necessary for the formation of heterochromatin in the budding yeast Saccharomyces cerevisiae. It has been implicated in a number of important processes including the regulation of yeast aging. Sir2 function is also known to be influenced by a variety of nutrients, including nitrogen, phosphorus, and carbon source. Even though Sir2 regulates aging and can respond to changes in nutrient availability, it is unknown whether Sir2 is involved in the well-documented and evolutionarily conserved extension of lifespan resulting from calorie restriction. Past studies have produced conflicting results, possibly due to experimental constraints that require the use of unbuffered minimal media for all experiments.
We have now developed an assay whereby yeast chronological aging can be studied in any media, allowing for Sir2’s aging role to be better understood. While Sir2 doesn’t seem to be involved in calorie restriction-mediated lifespan extension in minimal media, it does seem to be necessary for full calorie restriction-mediated lifespan extension in complex media. We have also shown for the first time that increasing glucose concentration alters Sir2-mediated heterochromatic silencing at the mating type locus HML, and that the directionality of this effect is opposite on minimal and complex media. Deletion of SIR2 also leads to opposite aging phenotypes during growth on minimal and complex media, leading to the exciting hypothesis that the stability of Sir2-based heterochromatic silencing at HML or some other Sir2 deacetylation target links glucose availability to aging dynamics.