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The Interaction of Aging, Caloric Restriction, and the Sulfur Assimilation pathway explored via Quantitative Time-lapse Flow Cytometry


Both Caloric Restriction (CR) and Methionine Restriction (MR) extend lifespan in many organisms. Recent results have shown that excess methionine can prevent lifespan extension by CR, suggesting that both MR and CR act by related mechanisms. Reporter strains' expression for genes involved in the sulfur assimilation pathway, as well as a handful of genes suspected to be involved in aging, were measured in a variety of metabolic conditions including CR and MR. By measuring expression levels over time, it was possible to determine the strength and speed of each gene's response to each stimulus. Notably, while large parts of the sulfur assimilation pathway responded to MR, parts only responded to GCN-4 activation via 3-AT, and oxidative stress response genes did not respond significantly to either stress. Met4p, the central sulfur assimilation pathway transcription factor, showed a unique response, by increasing transcriptionally in response to MR, but when glucose was absent. Future experiments can be built off of the tools built here, in order to gain an even deeper understanding of both the aging process as well as the sulfur assimilation pathway.

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