Heat Stress-Induced Life Span Extension in Yeast

Abstract

The yeastSaccharomyces cerevisiaehas a limited life span that can be measured by the number of times individual cells divide. Several genetic manipulations have been shown to prolong the yeast life span. However, environmental effects that extend longevity have been largely ignored. We have found that mild, nonlethal heat stress extended yeast life span when it was administered transiently early in life. The increased longevity was due to a reduction in the mortality rate that persisted over many cell divisions (generations) but was not permanent. The genesRAS1andRAS2were necessary to observe this effect of heat stress. TheRAS2gene is consistently required for 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 chronic heat stress. This distinction between theRASgenes may be partially related to their different effects on growth-promoting genes and stress-responsive genes. Theras2mutation clearly hindered resumption of growth and recovery from stress, while theras1mutation did not. TheHSP104gene, 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 theRASgenes and mitochondria may play a role in the epigenetic inheritance of reduced mortality rate afforded by transient, mild heat stress.