Wine yeast sirtuins and Gcn5p control aging and metabolism in a natural growth medium

Grape juice fermentation by wine yeast is an interesting model to understand aging under conditions closer to those in nature. Grape juice is rich in sugars and, unlike laboratory conditions, the limiting factor for yeast growth is nitrogen. We tested the effect of deleting sirtuins and several acetyltransferases to find that the role of many of these proteins during grape juice fermentation is the opposite to that under standard laboratory aging conditions using synthetic complete media. For instance, SIR2 deletion extends maximum chronological lifespan in wine yeasts grown under laboratory conditions, but shortens it in winemaking. Deletions of sirtuin HST2 and acetyltransferase GCN5 have the opposite effect to SIR2 mutation in both media. Acetic acid, a well known pro-aging compound in laboratory conditions, does not play a determinant role on aging during wine fermentation. We discovered that gcn5Δ mutant strain displays strongly increased aldehyde dehydrogenase Ald6p activity, caused by blocking of Ald6p degradation by autophagy under nitrogen limitation conditions, leading to acetic acid accumulation. We describe how nitrogen limitation and TOR inhibition extend the chronological lifespan under winemaking conditions and how the TOR-dependent control of aging partially depends on the Gcn5p function.