Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae

J Cell Biol. 2004 Sep 27;166(7):1055-67. doi: 10.1083/jcb.200404002.


Aging is believed to be a nonadaptive process that escapes the force of natural selection. Here, we challenge this dogma by showing that yeast laboratory strains and strains isolated from grapes undergo an age- and pH-dependent death with features of mammalian programmed cell death (apoptosis). After 90-99% of the population dies, a small mutant subpopulation uses the nutrients released by dead cells to grow. This adaptive regrowth is inversely correlated with protection against superoxide toxicity and life span and is associated with elevated age-dependent release of nutrients and increased mutation frequency. Computational simulations confirm that premature aging together with a relatively high mutation frequency can result in a major advantage in adaptation to changing environments. These results suggest that under conditions that model natural environments, yeast organisms undergo an altruistic and premature aging and death program, mediated in part by superoxide. The role of similar pathways in the regulation of longevity in organisms ranging from yeast to mice raises the possibility that mammals may also undergo programmed aging.

Publication types

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

MeSH terms

  • Adaptation, Physiological / genetics*
  • Aging / genetics
  • Aging / metabolism*
  • Aging, Premature / genetics
  • Aging, Premature / metabolism
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cells, Cultured
  • Culture Media / pharmacology
  • Environment
  • Hydrogen Peroxide / pharmacology
  • Mutation / drug effects
  • Mutation / genetics
  • Oxidative Stress / genetics
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Species Specificity
  • Starvation
  • Superoxides / metabolism*


  • Culture Media
  • Superoxides
  • Hydrogen Peroxide