Transcriptional remodeling in response to transfer upon carbon-limited or metformin-supplemented media in S. cerevisiae and its effect on chronological life span.

ABSTRACT

One of the factors affecting chronological life span (CLS) in budding yeast is nutrient, especially carbon limitation. Aside from metabolites in the growth medium such as glucose, amino acids, and acetic acid, many pharmaceuticals have also been proven to alter CLS. Besides their impact on life span, these drugs are also prospective chemicals to treat the age-associated diseases, so the identification of their action mechanism and their potential side effects is of crucial importance. In this study, the effects of caloric restriction and metformin, a dietary mimetic pharmaceutical, on yeast CLS are compared. Saccharomyces cerevisiae cells grown in synthetic dextrose complete (SDC) up to mid-exponential phase were either treated with metformin or were subjected to glucose limitation. The impacts of these perturbations were analyzed via transcriptomics, and the common (stimulation of glucose uptake, induction of mitochondrial maintenance, and reduction of protein translation) and divergent (stimulation of aerobic respiration and reprogramming of respiratory electron transport chain (ETC)) cellular responses specific to each treatment were determined. These results revealed that both glucose limitation and metformin treatment stimulate CLS extension and involve the mitochondrial function, probably by creating an efficient mitochondria-to-nucleus signaling of either aerobic respiration or ETC signaling stimulation, respectively.