Saccharomyces cerevisiae goes through distinct metabolic phases during its replicative lifespan

A comprehensive description of the phenotypic changes during cellular aging is key towards unraveling its causal forces. Using recently developed experimental tools, which previously had enabled us to map age related changes in proteome and transcriptome (Janssens et al., 2015), and model-based inference methods, here, we generated a comprehensive account of the metabolic changes during the entire replicative life of Saccharomyces cerevisiae . With age, we found decreasing metabolite levels, decreasing growth and substrate uptake rates accompanied by a switch from aerobic fermentation to a respiratory metabolism, with increased glycerol and acetate production. The identification of intracellular metabolic fluxes revealed an increase in redox cofactor turnover, likely to combat the increased production of reactive oxygen species. The identified metabolic changes possibly reflect a dynamic adaptation to the age-associated, non homeostatic increase in volume. With metabolism being an important factor of the cellular phenotype, this work complements our recent mapping of the transcriptomic and proteomic changes towards a holistic description of the cellular processes during aging.