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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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Substrate consumption during chronological aging in S. cerevisiae.Glucose (Panels A and D), ethanol (Panels B and E) and glycerol (Panel C and F) concentrations in the culture media during WT (Panels A-C) and ρ0 (Panels D-F) S. cerevisiae chronological lifespan were measured as described in Materials and Methods.
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pone-0056388-g002: Substrate consumption during chronological aging in S. cerevisiae.Glucose (Panels A and D), ethanol (Panels B and E) and glycerol (Panel C and F) concentrations in the culture media during WT (Panels A-C) and ρ0 (Panels D-F) S. cerevisiae chronological lifespan were measured as described in Materials and Methods.

Mentions: Differences in respiratory rates between control and CR cells have been attributed to the repressive effect of glucose on genes that encode proteins involved in aerobic metabolism, a phenomenon known as glucose repression [8], [13], [36]–[38]. Interestingly, however, glucose is exhausted from the culture media by the 24th h for control conditions and 18th h for CR (Fig. 2A, [39]). Thus, the most prominent changes in oxygen consumption rates observed in Fig. 1 occur many hours after no glucose can be detected in the culture media, indicating that cells grown under CR conditions hysteretically increase respiratory metabolism faster and to higher levels after glucose exhaustion. We questioned if this difference was due to a lower availability of oxidizable substrates for cells cultured under control conditions. However, measurements of ethanol and glycerol (Fig. 2B and C) indicate that levels of these substrates are higher in control cultures at these time points, and that they are exhausted much later than in CR cultures.


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)

Substrate consumption during chronological aging in S. cerevisiae.Glucose (Panels A and D), ethanol (Panels B and E) and glycerol (Panel C and F) concentrations in the culture media during WT (Panels A-C) and ρ0 (Panels D-F) S. cerevisiae chronological lifespan were measured as described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0056388-g002: Substrate consumption during chronological aging in S. cerevisiae.Glucose (Panels A and D), ethanol (Panels B and E) and glycerol (Panel C and F) concentrations in the culture media during WT (Panels A-C) and ρ0 (Panels D-F) S. cerevisiae chronological lifespan were measured as described in Materials and Methods.
Mentions: Differences in respiratory rates between control and CR cells have been attributed to the repressive effect of glucose on genes that encode proteins involved in aerobic metabolism, a phenomenon known as glucose repression [8], [13], [36]–[38]. Interestingly, however, glucose is exhausted from the culture media by the 24th h for control conditions and 18th h for CR (Fig. 2A, [39]). Thus, the most prominent changes in oxygen consumption rates observed in Fig. 1 occur many hours after no glucose can be detected in the culture media, indicating that cells grown under CR conditions hysteretically increase respiratory metabolism faster and to higher levels after glucose exhaustion. We questioned if this difference was due to a lower availability of oxidizable substrates for cells cultured under control conditions. However, measurements of ethanol and glycerol (Fig. 2B and C) indicate that levels of these substrates are higher in control cultures at these time points, and that they are exhausted much later than in CR cultures.

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