Calorie restriction hysteretically primes aging Saccharomyces cerevisiae toward more effective oxidative metabolism

PLoS One. 2013;8(2):e56388. doi: 10.1371/journal.pone.0056388. Epub 2013 Feb 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomass
  • Caloric Restriction
  • Cell Respiration
  • Cell Survival
  • Culture Media / chemistry
  • Energy Metabolism
  • Glucose / metabolism
  • Hydrogen-Ion Concentration
  • Mitochondria / metabolism
  • Oxidation-Reduction
  • Oxygen / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Time Factors

Substances

  • Culture Media
  • Glucose
  • Oxygen

Grants and funding

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), Conselho Nacional de Pesquisa e Desenvolvimento (CNPq), Instituto Nacional de Ciência e Tecnologia de Processos Redox em Biomedicina (INCT Redoxoma), Núcleo de Apoio à Pesquisa Redoxoma (NAP Redoxoma) and the John Simon Guggenheim Memorial Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.