Replicative aging as a source of cell heterogeneity in budding yeast.

While deviations from the optimal phenotype are deleterious, increased variation can prevent population extinction under severe stresses. Cell division asymmetry is an important source of microbial phenotypic heterogeneity. A consecutive set of asymmetric divisions can cause the gradual accumulation of deleterious factors and, at late stages, the death of old pole (mother) cells. This phenomenon is known as replicative aging. As the old cells are constantly being diluted by the progeny, the majority of a microbial population is represented by replicatively young cells. Therefore, early-age changes in yeast mother cells have a much greater impact on the integral performance of the microbial population than does functional deterioration at later ages. Here, we review the early manifestations of replicative aging in Saccharomyces cerevisiae mother cells that occur during the first ten cell cycles. Early age-dependent changes occur in stress resistance, genomic instability, protein aggregate levels, redox balance and metabolism. We speculate that some of these manifestations can be beneficial during stress exposure; therefore, early aging may be a bet-hedging mechanism. Together, the data suggest that the age component of variation in populations of asymmetrically dividing microorganisms is substantial and may play an important role in adaptations to changing environments.