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The initial goal of Dr. Kaeberlein’s project was to determine the feasibility of genome-wide
chronologic and replicative life span analysis using the approximately 4800 strains in Saccharomyces
cerevisiae Genome Deletion Project ORF deletion collection. In order to accomplish this, he has
performed replicative and chronologic aging assay on approximately 50 strains, all of which have
been reported to affect either RLS or CLS in a shorter-lived strain background. By collecting this
data set, Dr. Kaeberlein have been able to (1) optimize the chronologic aging assay for genome-wide
analysis, (2) perform statistical analysis of replicative life span data to determine the minimal
number of cells of a given strain needed to identify long-lived mutants, (3) compare the correlation
between chronological and replicative life span across a large number of strains, and (4) uncover
novel biological insights into the aging process in yeast. We are currently carrying out a
genome-wide quantitative analysis of chronological life span and have begun a genome-wide
quantitative analysis of replicative life span, with approximately 2% of the genome completed.
One particularly interesting result to come from the preliminary analysis is that in a long-lived
fob1 background, calorie restriction extends replicative life span even in cells lacking the Sir2
histone deacetylase. We have developed a molecular model to explain this observation and are
carrying out further experiments to identify the factors responsible for calorie
restriction-mediated replicative life span extension in yeast.
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