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

Abstract

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.

Assessment of chronological lifespan dependent molecular damages in yeast lacking mitochondrial antioxidant genes

“…Genomic instability and the rate at which genomic instability occurs have been shown to increase during aging [27][28][29][30]. Our results also show that the rate of spontaneous mutations was higher in old cells, especially for sod1D, ccs1D, and glo4D strains (Fig.…”

Isc1p Plays a Key Role in Hydrogen Peroxide Resistance and Chronological Lifespan through Modulation of Iron Levels and Apoptosis

“…Yeast apoptosis is induced by oxidative stress and during aging (Madeo et al, 1999(Madeo et al, , 2002Fabrizio et al, 2004;Herker et al, 2004), and sphingolipids have been implicated in the regulation of this process in mammalian cells . Therefore we postulated that Isc1p deficiency might increase cell death by apoptosis.…”

Apoptosis in yeast: triggers, pathways, subroutines

“…8 For example, during aging or development of multicellular colonies, where death of older and damaged cells preserves vanishing resources; thereby, dead cells release nutrients, differentiation molecules, and as yet unidentified pro-survival factors that can be metabolized and stimulate the survival of younger and fitter cells. 4,[9][10][11] In addition, increased ROS production accompanying enhanced cell death raises the probability of somatic mutations in the rest of the population and, thus, generation of genetic variants that can adapt to continuously changing conditions. In fact, regrowth of a subpopulation of betteradapted mutants has been shown to partly depend on the superoxide levels.…”

“…In fact, regrowth of a subpopulation of betteradapted mutants has been shown to partly depend on the superoxide levels. 9 Coupling cell death control to the process of aging limits single cell longevity, thus avoiding the maintenance of ancient genetic variants within the population and hindering genetic conservatism. During failed mating, mating-type pheromones trigger cell death to clean the culture from infertile or otherwise damaged haploid cells, thus guaranteeing the adaptive benefit of the diploid state, which allows meiotic recombination and the resulting genetic diversity.…”