Metabolism and aging: oxidative stress and chronological lifespan in Saccharomyces cerevisiae strains with single deletions in glycogen metabolism

CRISTIÁN FAVRE; MARÍA CRISTINA CARRILLO

Varsovia, Polonia

Conferencia; SENECA, European Conference on Cancer and Ageing 2007; 2007

SENECA, Unión Europea

Chronological aging in yeast represents an interestingmodel because of its resemblance with aging in mammalian,post-mitotic tissues, that show low proliferationbut conserved metabolic activity. The survival in the stationaryphase in yeast is strongly associated with oxidative-stress resistance. In the present study hypo- andhyper-glycogenic phenotypes of S. cerevisiae strains withdeletions (Euroscarf, Yeast Deletion Project) of glucidicmetabolismenzymes were selected, a comparison of theirchronological lifespans was achieved, and the followingassays were performed in the emerged candidates:stress sensitivity, ROS levels, and apoptosis markers duringaging. Between the strains that accumulated greateramounts of glycogen, the deletion of glycogen phosphorylase,gph1 (59 vs 29 g glycogen/108 cel. in wt. P < 0.05),was the unique in showing a shortened lifespan, stressintolerance, and higher levels of ROS during its survival.The transcription of SOD1 and 2 were analyzed in gph1,the transcript levels being 4- and 3-fold lower than in wtat the end of the stationary phase (8 and 5 vs 31 and 16UA in wt, respectively. P < 0.05), and during aging. Hypoglycogenicdeletions as the one of glycogen synthase,gsy2(8 g/108 cel. P < 0.05), demonstrated a little longevityadvantage but similar stress tolerance, ROS andRNA levels of SOD1/2 compared with the wt. Low-copyplasmid-mediated overexpression of SOD1 and SOD2together rescued gph1from its accelerated aging andstressed phenotype.The incapability to degrade glycogen (deletion of GPH1),produced a strain with rapid-aging that would be attributed,at least in part, to the impoverished stress resistanceassociated to the decreased transcript levels of both SODin this mutant. It remains to further clarify the putativedialogue between glycogen availability and the negativeregulation of these genes in the aging process.