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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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Glucose-to-biomass, glucose-to-ethanol and glucose-to-glycerol conversion factors.Glucose-to-biomass (YX/Gluexp, Panel A), glucose-to-ethanol (YEtOH/Gluexp, Panel B) and glucose-to-glycerol (YGly/Gluexp, Panel C) conversion factors in WT and ρ0S. cerevisiae were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).
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pone-0056388-g007: Glucose-to-biomass, glucose-to-ethanol and glucose-to-glycerol conversion factors.Glucose-to-biomass (YX/Gluexp, Panel A), glucose-to-ethanol (YEtOH/Gluexp, Panel B) and glucose-to-glycerol (YGly/Gluexp, Panel C) conversion factors in WT and ρ0S. cerevisiae were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).

Mentions: We also determined glucose-to-cells (YX/Gluexp, Fig. 7A), glucose-to-ethanol (YEtOH/Gluexp, Fig. 7B) and glucose-to-glycerol (YGly/Gluexp, Fig. 7C) conversion factors during the time periods glucose was available in the culture media (Table 1). Interestingly, glycerol formation from glucose (Fig. 7C) was higher in ρ0 mutants compared to WT cells, and WT CR cells presented a trend (p  =  0.07) toward higher glucose-to-glycerol conversion compared to control cells. However, we found that ρ0 mutants do not exhibit reduced glucose to cell conversion (Fig. 7A) or increased glucose-to-ethanol conversion (Fig. 7B) when compared to WT cells. Additionally, CR does not alter these physiological parameters. This leads to the surprising conclusion that the ability to generate biomass and to form ethanol from glucose is independent of the integrity of the mitochondrial genome and is not changed by the amount of glucose available in the culture media at the beginning of the culture period.


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)

Glucose-to-biomass, glucose-to-ethanol and glucose-to-glycerol conversion factors.Glucose-to-biomass (YX/Gluexp, Panel A), glucose-to-ethanol (YEtOH/Gluexp, Panel B) and glucose-to-glycerol (YGly/Gluexp, Panel C) conversion factors in WT and ρ0S. cerevisiae were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0056388-g007: Glucose-to-biomass, glucose-to-ethanol and glucose-to-glycerol conversion factors.Glucose-to-biomass (YX/Gluexp, Panel A), glucose-to-ethanol (YEtOH/Gluexp, Panel B) and glucose-to-glycerol (YGly/Gluexp, Panel C) conversion factors in WT and ρ0S. cerevisiae were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).
Mentions: We also determined glucose-to-cells (YX/Gluexp, Fig. 7A), glucose-to-ethanol (YEtOH/Gluexp, Fig. 7B) and glucose-to-glycerol (YGly/Gluexp, Fig. 7C) conversion factors during the time periods glucose was available in the culture media (Table 1). Interestingly, glycerol formation from glucose (Fig. 7C) was higher in ρ0 mutants compared to WT cells, and WT CR cells presented a trend (p  =  0.07) toward higher glucose-to-glycerol conversion compared to control cells. However, we found that ρ0 mutants do not exhibit reduced glucose to cell conversion (Fig. 7A) or increased glucose-to-ethanol conversion (Fig. 7B) when compared to WT cells. Additionally, CR does not alter these physiological parameters. This leads to the surprising conclusion that the ability to generate biomass and to form ethanol from glucose is independent of the integrity of the mitochondrial genome and is not changed by the amount of glucose available in the culture media at the beginning of the culture period.

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