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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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Biomass formation is altered by glucose levels and respiratory integrity.Biomass values during WT and ρ0S. cerevisiae (Panels A-A’ and B-B’, respectively) chronological aging were measured as described in Materials and Methods. Panels A’ and B’ show a reduced time scale of the exponential growth phase.
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pone-0056388-g005: Biomass formation is altered by glucose levels and respiratory integrity.Biomass values during WT and ρ0S. cerevisiae (Panels A-A’ and B-B’, respectively) chronological aging were measured as described in Materials and Methods. Panels A’ and B’ show a reduced time scale of the exponential growth phase.

Mentions: We followed cell growth by measuring Abs600 of the culture media and determining the conversion factor between Abs600 and biomass, as described in Materials and Methods. We found (Fig. 5A) that the biomass formed after 28 days by WT cells cultured under CR conditions was 38.50±1.64% lower than that formed by control cells. This observation, together with the fact that the CR medium provides 75% less glucose, indicates that the efficiency of energy conversion exhibited by CR cells is increased.


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)

Biomass formation is altered by glucose levels and respiratory integrity.Biomass values during WT and ρ0S. cerevisiae (Panels A-A’ and B-B’, respectively) chronological aging were measured as described in Materials and Methods. Panels A’ and B’ show a reduced time scale of the exponential growth phase.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0056388-g005: Biomass formation is altered by glucose levels and respiratory integrity.Biomass values during WT and ρ0S. cerevisiae (Panels A-A’ and B-B’, respectively) chronological aging were measured as described in Materials and Methods. Panels A’ and B’ show a reduced time scale of the exponential growth phase.
Mentions: We followed cell growth by measuring Abs600 of the culture media and determining the conversion factor between Abs600 and biomass, as described in Materials and Methods. We found (Fig. 5A) that the biomass formed after 28 days by WT cells cultured under CR conditions was 38.50±1.64% lower than that formed by control cells. This observation, together with the fact that the CR medium provides 75% less glucose, indicates that the efficiency of energy conversion exhibited by CR cells is increased.

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