Chronological lifespan and oxidative stress in Saccharomyces cerevisiae strains with single deletions in glucidic metabolism

CRISTIÁN FAVRE; MARÍA CRISTINA CARRILLO

Montevideo, Uruguay

Congreso; V Meeting of SFRBM South American Group Septiembre 2007; 2007

Society for Free Radical Biology and Medicine

Chronological aging in yeast represents an interesting model because of its resemblance with aging in mammalian, post-mitotic tissues, that show low proliferation but conserved metabolic activity. The survival in the stationary phase in yeast is strongly associated with oxidative-stress resistance. In the present study hypo- and hyper-glycogenic phenotypes of S. cerevisiae strains with deletions (Euroscarf, Yeast Deletion Project) of glucose-metabolism enzymes were selected, a comparison of their chronological lifespans was achieved, and the following assays were performed in the emerged candidates: stress sensitivity, ROS levels, and apoptosis markers during aging. Among the strains that accumulated greater amounts of glycogen, the deletion of glycogen phosphorylase, gph1Δ (59 vs. 29 μg glycogen/108 cel. in wt. p<.05), was the unique in showing a shortened lifespan, stress intolerance, and higher levels of ROS during its survival. The transcription of SOD1 and 2 were analyzed in gph1Δ, the transcript levels being 4- and 3-fold lower than in wt at the end of the stationary phase (8 and 5 vs. 31 and 16 AU in wt, respectively. p<.05), and during aging. Hypo-glycogenic deletions such as the one of glycogen synthase, gsy2Δ (8 μg/108 cel. p<.05), demonstrated a little longevity advantage but similar stress tolerance, ROS and RNA levels of SOD1/2 compared with the wt. Low-copy-plasmid-mediated overexpression of SOD1 and SOD2 together rescued gph1Δ from its accelerated aging and stressed phenotype. The incapability to degrade glycogen (deletion of GPH1), produced a rapid-aging strain, what would be attributed, at least in part, to the impoverished stress resistance associated to the decreased transcript levels of both SOD in this mutant. It remains to further clarify the putative dialogue between glycogen availability and the negative regulation of these genes in the aging process.