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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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Maximum specific generation of ethanol/glycerol, specific growth rate in ethanol/glycerol, maximum specific consumption of ethanol/glycerol and ethanol/glycerol-to-cell conversion factors.Maximum specific generation of ethanol/glycerol (rfEtOH+Glymax, Panel A), specific growth rate in ethanol/glycerol (μEtOH+Glymax, Panel B), maximum specific consumption of ethanol/glycerol (rcEtOH+Glymax, Panel C) and ethanol/glycerol-to-cells conversion factors (YXEtOH+ Glymax, Panel D) were calculated as described in Materials and Methods. Panel A: *p <0.05 vs. 2.0%; +p < 0.05 vs. WT (unpaired Student's t test).
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pone-0056388-g008: Maximum specific generation of ethanol/glycerol, specific growth rate in ethanol/glycerol, maximum specific consumption of ethanol/glycerol and ethanol/glycerol-to-cell conversion factors.Maximum specific generation of ethanol/glycerol (rfEtOH+Glymax, Panel A), specific growth rate in ethanol/glycerol (μEtOH+Glymax, Panel B), maximum specific consumption of ethanol/glycerol (rcEtOH+Glymax, Panel C) and ethanol/glycerol-to-cells conversion factors (YXEtOH+ Glymax, Panel D) were calculated as described in Materials and Methods. Panel A: *p <0.05 vs. 2.0%; +p < 0.05 vs. WT (unpaired Student's t test).

Mentions: The lack of a change in glucose-to-cell conversion promoted by CR (Fig. 7A) associated with the higher efficiency of energy conversion observed in CR cells when measuring growth curves (Fig. 5) suggests CR increases metabolic efficiency with other substrates. Thus, we determined the conversion factors for respiratory substrates (Fig. 8). Since ethanol and glycerol consumption are temporally parallel (Fig. 4B and C), the maximum specific growth rate in ethanol and glycerol could not be separately obtained, and the calculation of the formation, consumption and conversion factor to cells of both substrates was performed together, at the time intervals depicted in 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)

Maximum specific generation of ethanol/glycerol, specific growth rate in ethanol/glycerol, maximum specific consumption of ethanol/glycerol and ethanol/glycerol-to-cell conversion factors.Maximum specific generation of ethanol/glycerol (rfEtOH+Glymax, Panel A), specific growth rate in ethanol/glycerol (μEtOH+Glymax, Panel B), maximum specific consumption of ethanol/glycerol (rcEtOH+Glymax, Panel C) and ethanol/glycerol-to-cells conversion factors (YXEtOH+ Glymax, Panel D) were calculated as described in Materials and Methods. Panel A: *p <0.05 vs. 2.0%; +p < 0.05 vs. WT (unpaired Student's t test).
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Related In: Results  -  Collection

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

pone-0056388-g008: Maximum specific generation of ethanol/glycerol, specific growth rate in ethanol/glycerol, maximum specific consumption of ethanol/glycerol and ethanol/glycerol-to-cell conversion factors.Maximum specific generation of ethanol/glycerol (rfEtOH+Glymax, Panel A), specific growth rate in ethanol/glycerol (μEtOH+Glymax, Panel B), maximum specific consumption of ethanol/glycerol (rcEtOH+Glymax, Panel C) and ethanol/glycerol-to-cells conversion factors (YXEtOH+ Glymax, Panel D) were calculated as described in Materials and Methods. Panel A: *p <0.05 vs. 2.0%; +p < 0.05 vs. WT (unpaired Student's t test).
Mentions: The lack of a change in glucose-to-cell conversion promoted by CR (Fig. 7A) associated with the higher efficiency of energy conversion observed in CR cells when measuring growth curves (Fig. 5) suggests CR increases metabolic efficiency with other substrates. Thus, we determined the conversion factors for respiratory substrates (Fig. 8). Since ethanol and glycerol consumption are temporally parallel (Fig. 4B and C), the maximum specific growth rate in ethanol and glycerol could not be separately obtained, and the calculation of the formation, consumption and conversion factor to cells of both substrates was performed together, at the time intervals depicted in 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