Calorie restriction-mediated replicative lifespan extension in yeast is non-cell autonomous

PLoS Biol. 2015 Jan 29;13(1):e1002048. doi: 10.1371/journal.pbio.1002048. eCollection 2015 Jan.

Abstract

In laboratory yeast strains with Sir2 and Fob1 function, wild-type NAD+ salvage is required for calorie restriction (CR) to extend replicative lifespan. CR does not significantly alter steady state levels of intracellular NAD+ metabolites. However, levels of Sir2 and Pnc1, two enzymes that sequentially convert NAD+ to nicotinic acid (NA), are up-regulated during CR. To test whether factors such as NA might be exported by glucose-restricted mother cells to survive later generations, we developed a replicative longevity paradigm in which mother cells are moved after 15 generations on defined media. The experiment reveals that CR mother cells lose the longevity benefit of CR when evacuated from their local environment to fresh CR media. Addition of NA or nicotinamide riboside (NR) allows a moved mother to maintain replicative longevity despite the move. Moreover, conditioned medium from CR-treated cells transmits the longevity benefit of CR to moved mother cells. Evidence suggests the existence of a longevity factor that is dialyzable but is neither NA nor NR, and indicates that Sir2 is not required for the longevity factor to be produced or to act. Data indicate that the benefit of glucose-restriction is transmitted from cell to cell in budding yeast, suggesting that glucose restriction may benefit neighboring cells and not only an individual cell.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Caloric Restriction
  • Culture Media, Conditioned
  • Gene Expression Regulation, Fungal
  • Glucose / metabolism
  • Microbial Viability
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / physiology*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / physiology
  • Sirtuin 2 / physiology

Substances

  • Culture Media, Conditioned
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • SIR2 protein, S cerevisiae
  • Sirtuin 2
  • Glucose

Grant support

Work was supported by National Science Foundation grant MCB-1322118 to CB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.