Abstract

The unicellular eukaryotic organisms represent the popular model systems to understand aging in eukaryotes. Candida albicans, a polymorphic fungus, appears to be another distinctive unicellular aging model in addition to the budding yeast Saccharomyces cerevisiae and fission yeast Schizosaccharomyces pombe. The two types of Candida cells, yeast (blastospore) form and hyphal (filamentous) form, have similar replicative lifespan. Taking the advantage of morphologic changes, we are able to obtain cells of different ages. Old Candida cells tend to accumulate glycogen and oxidatively damaged proteins. Deletion of the SIR2 gene causes a decrease of lifespan, while insertion of an extra copy of SIR2 extends lifespan, indicating that like in S. cerevisiae, Sir2 regulates cellular aging in C. albicans. Interestingly, Sir2 deletion does not result in the accumulation of extra-chromosomal rDNA molecules, but influences the retention of oxidized proteins in mother cells, suggesting that the extra-chromosomal rDNA molecules may not be associated with cellular aging in C. albicans. This novel aging model, which allows efficient large-scale isolation of old cells, may facilitate biochemical characterizations and genomics/proteomics studies of cellular aging, and help to verify the aging pathways observed in other organisms including S. cerevisiae.

Highlights

  • Aging is usually defined as the progressive loss of function accompanied by decreasing fertility and increasing mortality with advancing age (Kirkwood & Austad, 2000)

  • These results demonstrate that both yeast and hyphal form cells have finite replicative lifespan

  • Our data suggest that C. albicans could be used as a model to study cellular aging

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Summary

Introduction

Aging is usually defined as the progressive loss of function accompanied by decreasing fertility and increasing mortality with advancing age (Kirkwood & Austad, 2000). Lifespan regulation is evolutionarily conserved, and found in various species ranging from eukaryotic multicellular (e.g. humans) to unicellular (e.g. yeast), and to prokaryotic (e.g. Escherichia coli) organisms (Stewart et al, 2005). The budding yeast Saccharomyces cerevisiae, which divides asymmetrically, is a unicellular eukaryotic organism with a short and studied lifespan, and enables researchers to chase an individual cell through many cell divisions. The yeast cells undergo a limited number of cell divisions before senescence, and small budding daughter cells come from the larger aging mother cells in most of the lifespan. The total number of daughter cells produced by a mother cell prior to senescence is defined as the replicative lifespan of the mother cell (Mortimer & Johnston, 1959). Aging in yeasts S. cerevisiae and Schizosaccharomyces pombe has been measured as the length of time a population stay alive; it is referred to as chronological aging (Fabrizio & Longo, 2003; Roux et al, 2006)

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