DIFFERENTIAL RESPONSE TO UV STRESS AND DNA-DAMAGE DURING THE YEAST REPLICATIVE LIFE-SPAN

The yeast Saccharomyces cerevisiae is mortal. Before they die, individ ual yeasts bud repeatedly producing a finite number of progeny, which have the capacity for a full life span. A feature of aging in many spe cies is the waning of resistance to stress. To determine whether this is the case in yeast, we have examined the survival (viability) of age -synchronized populations of yeasts of various ages, spanning youth, m idlife, a nd old age, after irradiation with ultraviolet light (UV). R esistance to UV was biphasic. There was an increase through midlife, f ollowed by a precipitous decline. For comparison, another mutagenic ag ent, ethyl methanesulfonate (EMS), was tested in the same way. The res ponse was very different. A uniphase decrease in resistance to this DN A-alkylating agent was found with a plateau later in life. The results argue that the increase in resistance to UV with age is an active pro cess a nd not sim ply a monotonic age change. RAS2 is among the genes that determine yeast longevity. This gene is preferentially expressed in young cells and has a life span-extending effect on yeasts. One kno wn function of RAS2 is to mount a protective response to irradiation b y UV, which occurs independently of DNA damage. The distinction betwee n UV and EMS found here is consistent with the notion that resistance to UV plays a role in yeast longevity in a manner not related to DNA d amage. Furthermore, it suggests that RAS2 may participate in this resp onse. We have found that RAS2 expression and UV resistance coincide in middle-aged yeasts bolstering this possibility. These data and the ec lipse in activity of several longevity determining genes at midlife in yeasts also raise the possibility that active life maintenance proces ses function through this period, after which the organism operates on any remaining reserves until death. (C) 1996 Wiley-Liss, Inc.