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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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Specific growth rate and specific glucose consumption are decreased in ρ0S. cerevisiae but unaltered by glucose levels.Specific growth rates in glucose (μglumax, Panel A) and specific glucose consumption (rglumax, Panel B) of WT and ρ0S. cerevisiae (as indicated) were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).
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pone-0056388-g006: Specific growth rate and specific glucose consumption are decreased in ρ0S. cerevisiae but unaltered by glucose levels.Specific growth rates in glucose (μglumax, Panel A) and specific glucose consumption (rglumax, Panel B) of WT and ρ0S. cerevisiae (as indicated) were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).

Mentions: Using the data presented in Fig. 2 and 5 and time intervals in which glucose was present in the media (Table 1), we were able to calculate specific cell growth rates on glucose (μGlumax, Fig. 6A) as well as maximal specific glucose consumption rates (rcGlumax, Fig. 6B) for ρ0 and WT S. cerevisiae cultured under control and CR conditions. We found that CR does not alter specific growth on glucose (Fig. 6A), but that ρ0 mutants present a significant reduction, both under control and CR conditions. Similarly, maximal specific glucose consumption rates did not differ between control and CR WT cells (Fig. 6B) but the absence of mitochondrial DNA decreases rcGlumax.


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)

Specific growth rate and specific glucose consumption are decreased in ρ0S. cerevisiae but unaltered by glucose levels.Specific growth rates in glucose (μglumax, Panel A) and specific glucose consumption (rglumax, Panel B) of WT and ρ0S. cerevisiae (as indicated) were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3569431&req=5

pone-0056388-g006: Specific growth rate and specific glucose consumption are decreased in ρ0S. cerevisiae but unaltered by glucose levels.Specific growth rates in glucose (μglumax, Panel A) and specific glucose consumption (rglumax, Panel B) of WT and ρ0S. cerevisiae (as indicated) were calculated as described in Materials and Methods. *p <0.05 vs. WT (unpaired Student's t test).
Mentions: Using the data presented in Fig. 2 and 5 and time intervals in which glucose was present in the media (Table 1), we were able to calculate specific cell growth rates on glucose (μGlumax, Fig. 6A) as well as maximal specific glucose consumption rates (rcGlumax, Fig. 6B) for ρ0 and WT S. cerevisiae cultured under control and CR conditions. We found that CR does not alter specific growth on glucose (Fig. 6A), but that ρ0 mutants present a significant reduction, both under control and CR conditions. Similarly, maximal specific glucose consumption rates did not differ between control and CR WT cells (Fig. 6B) but the absence of mitochondrial DNA decreases rcGlumax.

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