Heat stress-induced life span extension in yeast

The yeast Saccharomyces cerevisiae has a limited life span that can be meas ured by the number of times individual cells divide. Several genetic manipu lations have been shown to prolong the yeast life span. However, environmen tal effects that extend longevity have been largely ignored. We have found that mild, nonlethal heat stress extended yeast life span when it was admin istered transiently early in life. The increased longevity was due to a red uction in the mortality rate that persisted over many cell divisions (gener ations) but was not permanent. The genes RAS1 and RAS2 were necessary to ob serve this effect of heat stress. The RAS2 gene is consistently required fo r maintenance of life span when heat stress is chronic or in its extension when heat stress is transient or absent altogether. RAS1, on the other hand , appears to have a role in signaling life extension induced by transient, mild heat stress, which is distinct from its life-span-curtailing effect in the absence of stress and its lack of involvement in the response to chron ic heat stress. This distinction between the RAS genes may be partially rel ated to their different effects on growth-promoting genes and stress-respon sive genes. The ras2 mutation clearly hindered resumption of growth and rec overy from stress, while the ras1 mutation did not. The HSP104 gene, which is largely responsible for induced thermotolerance in yeast, was necessary for life extension induced by transient heat stress. An interaction between mitochondrial petite mutations and heat stress was found, suggesting that mitochondria may be necessary for life extension by transient heat stress. The results raise the possibility that the RAS genes and mitochondria may p lay a role in the epigenetic inheritance of reduced mortality rate afforded by transient, mild heat stress. (C) 1998 Academic Press.