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Calorie restriction hysteretically primes aging Saccharomyces cerevisiae toward more effective oxidative metabolism.

Tahara EB, Cunha FM, Basso TO, Della Bianca BE, Gombert AK, Kowaltowski AJ - PLoS ONE (2013)

Bottom Line: Here, we measured wild-type and respiratory incompetent (ρ(0)) S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR.Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol.Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0) cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, São Paulo, Brazil.

ABSTRACT
Calorie restriction (CR) is an intervention known to extend the lifespan of a wide variety of organisms. In S. cerevisiae, chronological lifespan is prolonged by decreasing glucose availability in the culture media, a model for CR. The mechanism has been proposed to involve an increase in the oxidative (versus fermentative) metabolism of glucose. Here, we measured wild-type and respiratory incompetent (ρ(0)) S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR. The concomitant and quantitative measurements allowed for calculations of conversion factors between different pairs of substrates and products, maximum specific substrate consumption and product formation rates and maximum specific growth rates. Interestingly, we found that the limitation of glucose availability in CR S. cerevisiae cultures hysteretically increases oxygen consumption rates many hours after the complete exhaustion of glucose from the media. Surprisingly, glucose-to-ethanol conversion and cellular growth supported by glucose were not quantitatively altered by CR. Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol. Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0) cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

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Oxygen consumption rates vary during WT S. cerevisiae chronological lifespan.Intact cellular respiratory rates of WT S. cerevisiae cultured in 2.0% glucose (▪) or 0.5% glucose (□) were measured as described in Materials and Methods. *p<0.05 vs. 2.0% WT (unpaired Student's t test).
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pone-0056388-g001: Oxygen consumption rates vary during WT S. cerevisiae chronological lifespan.Intact cellular respiratory rates of WT S. cerevisiae cultured in 2.0% glucose (▪) or 0.5% glucose (□) were measured as described in Materials and Methods. *p<0.05 vs. 2.0% WT (unpaired Student's t test).

Mentions: In order to understand how glucose levels in culture and oxidative metabolism are related to chronological aging, we quantified oxygen consumption rates in intact WT S. cerevisiae cells cultured under control and CR conditions in YPD during 28 days of chronological aging (Fig. 1). Interestingly, although respiratory activity is slightly higher in CR cells after 6 h in culture, maximal respiratory rates are observed much later. Furthermore, the maximum rate of oxygen consumption in S. cerevisiae under CR is significantly higher than that observed in control cells, and occurs 12 h earlier (at 33 h for 0.5% and 45 h for 2.0%). Indeed, from the 24th to the 42nd h of culture, oxygen consumption by CR cells is increased when compared to control cells. This time period coincides with the use of ethanol and glycerol as carbon sources by CR cells (Table 1).


Calorie restriction hysteretically primes aging Saccharomyces cerevisiae toward more effective oxidative metabolism.

Tahara EB, Cunha FM, Basso TO, Della Bianca BE, Gombert AK, Kowaltowski AJ - PLoS ONE (2013)

Oxygen consumption rates vary during WT S. cerevisiae chronological lifespan.Intact cellular respiratory rates of WT S. cerevisiae cultured in 2.0% glucose (▪) or 0.5% glucose (□) were measured as described in Materials and Methods. *p<0.05 vs. 2.0% WT (unpaired Student's t test).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3569431&req=5

pone-0056388-g001: Oxygen consumption rates vary during WT S. cerevisiae chronological lifespan.Intact cellular respiratory rates of WT S. cerevisiae cultured in 2.0% glucose (▪) or 0.5% glucose (□) were measured as described in Materials and Methods. *p<0.05 vs. 2.0% WT (unpaired Student's t test).
Mentions: In order to understand how glucose levels in culture and oxidative metabolism are related to chronological aging, we quantified oxygen consumption rates in intact WT S. cerevisiae cells cultured under control and CR conditions in YPD during 28 days of chronological aging (Fig. 1). Interestingly, although respiratory activity is slightly higher in CR cells after 6 h in culture, maximal respiratory rates are observed much later. Furthermore, the maximum rate of oxygen consumption in S. cerevisiae under CR is significantly higher than that observed in control cells, and occurs 12 h earlier (at 33 h for 0.5% and 45 h for 2.0%). Indeed, from the 24th to the 42nd h of culture, oxygen consumption by CR cells is increased when compared to control cells. This time period coincides with the use of ethanol and glycerol as carbon sources by CR cells (Table 1).

Bottom Line: Here, we measured wild-type and respiratory incompetent (ρ(0)) S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR.Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol.Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0) cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, São Paulo, Brazil.

ABSTRACT
Calorie restriction (CR) is an intervention known to extend the lifespan of a wide variety of organisms. In S. cerevisiae, chronological lifespan is prolonged by decreasing glucose availability in the culture media, a model for CR. The mechanism has been proposed to involve an increase in the oxidative (versus fermentative) metabolism of glucose. Here, we measured wild-type and respiratory incompetent (ρ(0)) S. cerevisiae biomass formation, pH, oxygen and glucose consumption, and the evolution of ethanol, glycerol, acetate, pyruvate and succinate levels during the course of 28 days of chronological aging, aiming to identify metabolic changes responsible for the effects of CR. The concomitant and quantitative measurements allowed for calculations of conversion factors between different pairs of substrates and products, maximum specific substrate consumption and product formation rates and maximum specific growth rates. Interestingly, we found that the limitation of glucose availability in CR S. cerevisiae cultures hysteretically increases oxygen consumption rates many hours after the complete exhaustion of glucose from the media. Surprisingly, glucose-to-ethanol conversion and cellular growth supported by glucose were not quantitatively altered by CR. Instead, we found that CR primed the cells for earlier, faster and more efficient metabolism of respiratory substrates, especially ethanol. Since lifespan-enhancing effects of CR are absent in respiratory incompetent ρ(0) cells, we propose that the hysteretic effect of glucose limitation on oxidative metabolism is central toward chronological lifespan extension by CR in this yeast.

Show MeSH
Related in: MedlinePlus