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KEY WORDS: yeast, senescence, longevity, ERC, extrachromosomal, rDNA, RAS, UTH, SGS 1
ABSTRACT
The budding yeast Sacc)Ruromyces cerevisiae divides asymmetrically, giving rise to a mother cell and a smaller daughter cell. Individual mother cells produce a finite number of daughter cells before senescing, undergoing characteristic changes as they age such as a slower cell cycle and sterility. The average life span is fixed for a given strain, implying that yeast aging has a strong genetic component. Genes that determine yeast longevity have highlighted the importance of such processes as cAMP metabolism, epigenetic silencing, and genome stability. The recent finding that yeast aging is caused, in part, by the accumulation of circular rDNA molecules has unified many seemingly disparate observations.
INTRODUCTION
The budding yeast Saccharomyces cerevisiae has been used as a model for replicative senescence and aging since 1959, when Mortimer & Johnston (84) first noted that individual yeast cells have a finite life span. Since then, much of yeast aging research remained descriptive, and many aging models have been proposed, then discounted. The 1990s have seen a concerted effort to understand the yeast aging process at a molecular level, driven in part by rapid advances in genetic and biochemical techniques. One of the most important advances in the field was the development of techniques to isolate large quantities of old cells, a requirement for any biochemical analysis of yeast aging.
Over the past few years, great progress has been made in identifying key genes in the yeast aging process, including those involved in metabolism, cell cycle control, and epigenetic silencing. One recent discovery has implicated DNA stability in the aging process and, in so doing, may have validated the yeast aging model that invokes a molecular aging clock timing the accumulation of a senescence factor.
AGING THEORIES: An Overview
Studies of model organisms such as Drosophila, Caenorhabditis elegans, and S. cerevisiae have revealed that many biological themes are highly conserved. Many eukaryotes experience an exponential decline in fitness and fecundity over time, most evident after the reproductive phase of life. In the absence of external influences that affect the mortality rate (such as parasitic disease or predation), a genetic component of aging may be seen. Many eukaryotic organisms have rates of survival...