Sir2-independent life span extension by calorie restriction or SCH9 deletion.
Matt Kaeberlein (1), Kathryn Kirkland (2), Stanley Fields (1), Brian Kennedy (2)
(1) Department of Genome Sciences, University of Washington, HSB K-222, Seattle, WA, 98195, USA;
(2) Department of Biochemistry, University of Washington, Seattle WA 98195
Enhanced longevity upon calorie restriction is widely conserved among eukaryotic organisms, including yeast. To better understand the factors regulating calorie restriction and aging in yeast, we performed an analysis of 42 single-gene deletions reported to affect replicative or chronological life span. This analysis was carried out in a long-lived strain background, and included three genetic models of calorie restriction: hxk2delta, gpa2delta, and gpr1delta. Of the strains examined, we find that only deletion of FOB1, a gene necessary for extrachromosomal rDNA circle formation; deletion of SCH9, a gene implicated in chronological aging and stress response; and calorie restriction significantly enhance replicative life span. Calorie restriction of cells lacking Fob1 results in a synergistic increase in life span that does not require the presence of Sir2, consistent with a model whereby calorie restriction acts in a pathway parallel to Sir2 and rDNA circles to promote longevity. Like calorie restriction, deletion of SCH9 also increases life span in a Sir2-independent, rDNA circle-independent manner, suggesting a link between replicative and chronological life span, with possible relevance to aging in higher eukaryotes. .
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