Chris Burtner

Mentor: Brian Kennedy
Box: 357350
Phone: 206-616-9484
Email: creid2@u.washington.edu

Chris Burtner is researching how dietary restriction (DR) increases the median and maximum lifespan of many model organisms, from yeast to mice. The lifespan of yeast can be measured in two ways. The replicative lifespan (RLS) is measured as the number of cell divisions that a single mother cell can perform before it can no longer divide. The chronological life span (CLS) of yeast is measured as the time that a population of stationary yeast remain viable when introduced to a nutrient replete environment.

While some interventions, like DR, extend both the RLS and CLS, we have discovered that many evolutionarily conserved genetic determinants of lifespan that extend the RLS do not extend chronological longevity. We recently demonstrated that chronological aging in defined medium results from metabolic production and accumulation of a cell-extrinsic factor that is present 48 hours after initiation of growth. Using HPLC we quantified several extracellular by-products of fermentative growth, and identified acetic acid as a potent mediator of cell death. Several environmental life span extending interventions, including dietary restriction and growth in the non-fermentable carbon source glycerol, can be explained by altered rates of acetic acid induced aging.

A variety of other interventions that increase yeast CLS, such as deletion of the S6 kinase homolog SCH9, deletion of RAS2, or growth in a high osmolarity medium, confers an acetic acid resistant phenotype to stationary yeast. Finally, the toxicity associated with extracellular acetic acid can be abrogated by transferring stationary cells to water or buffering the culture medium. These findings strongly support the hypothesis that acetic acid induced aging is a primary mechanism of chronological aging in yeast.

Publications
Burtner, C. R., Murakami, C. J., Kennedy, B. K., Kaeberlein, M. A mechanism of chronological aging in Saccharomyces cerevisiae. (submitted).

Kudlow, B. A., Stanfel M. N., Johnston, E. D., Burtner, C. R., Kennedy, B. K. Suppression of proliferative defects associated with processing-defective lamin A mutants by hTERT or inactivation of p53. (submitted).

Burtner, C. R., Murakami, C. J., Kaeberlein, M. A genomic approach to yeast chronological aging. Methods in Molecular Biology 2008 (in press).

Murakami, C. J., Burtner, C. R., Kennedy, B. K., Kaeberlein, M. A method for high throughput quantitative analysis of yeast chronological life span. J Gerontol A Biol Sci Med Sci 2008 63: 113-121.

Kaeberlein, M., Burtner, C., Kennedy, B. Recent developments in yeast aging. PLoS Genet. 2007;3:e84.