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

Abstract

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 gcn5 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.

Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking

“…Moreover, the role of Sir2 overexpression in aging in flies and worms has proved not to be as strong as previously assumed [27]. Previously, we proved that sirtuin deletion in wine yeasts affects CLS, often in a growth medium-dependent way [28]. For instance, Sir2 deletion extends CLS under laboratory conditions, but shortens it during grape juice fermentation.…”

Aging-related rotenone-induced neurochemical and behavioral deficits: role of SIRT2 and redox imbalance, and neuroprotection by AK-7

“…Increasing evidences indicate that sirtuins are involved in the regulation of a variety of biological activities, including chromosomal stability, transcriptional silencing, cell cycle progression, apoptosis, metabolism, autophagy, growth suppression, stress response, inflammation, and tumorigenesis 28,34–37. Recent work has implicated the role of sirtuins in the aging process and aging-related neurodegenerative diseases 25,38–41. In mam mals, there are seven known sirtuins, SIRT 1–7 35.…”

Two-carbon metabolites, polyphenols and vitamins influence yeast chronological life span in winemaking conditions

“…If this were the case, then our results would indicate that sirtuin activity is negative for CLS under winemaking conditions. We have previously shown that some sirtuins, like Sir2, play a positive role during grape juice fermentation, while others, like Hst2 and Hst3, perform a negative one [15]; therefore, the latter may be more relevant for CLS in fermentation than the former. Indeed, this would fit in with the fact that the addition of vitamins nicotinic acid and nicotinamide, which produce more NAD + and more sirtuin activity, also had a negative effect on CLS.…”

“…However under winemaking conditions, the impact of acetic acid on aging is prevented by grape juice’s highly buffered nature [15]. Another metabolite with an important role in aging is ethanol, which has a negative impact on the CLS of laboratory strains [16].…”

“…Sir2 gives its name to a family of enzymes called sirtuins which, in yeast, includes four other members, Hst1 to Hst4. We have seen that these enzymes play positive and negative roles in CLS in wine yeast, and that these roles depend on the nature of the growth media [15]. Grape polyphenol resveratrol has been linked to sirtuin activation and life span extension, although this topic is the center of bitter controversy [19].…”