title: At neutral pH the chronological lifespan ofHansenula polymorphaincreases upon enhancing the carbon source concentrations.
abstract: Dietary restriction is generally assumed to increase the lifespan in most eukaryotes, including the simple model organismSaccharomyces cerevisiae. However, recent data questioned whether this phenomenon is indeed true for yeast. We studied the effect of reduction of the carbon source concentration on the chronological lifespan of the yeastHansenula polymorphausing four different carbon sources. Our data indicate that reduction of the carbon source concentration has a negative (glucose, ethanol, methanol) or positive (glycerol) effect on the chronological lifespan. We show that the actual effect of carbon source concentrations largely depends on extracellular factor(s). We provide evidence thatH. polymorphaacidifies the medium and that a low pH of the medium alone is sufficient to significantly decrease the chronological lifespan. However, glucose-grown cells are less sensitive to low pH compared to glycerol-grown cells, explaining why only the reduction of the glycerol-concentration (which leads to less medium acidification) has a positive effect on the chronological lifespan. Instead, the positive effect of enhancing the glucose concentrations is much larger than the negative effect of the medium acidification at these conditions, explaining the increased lifespan with increasing glucose concentrations. Importantly, at neutral pH, the chronological lifespan also decreases with a reduction in glycerol concentrations. We show that for glycerol cultures this effect is related to acidification independent changes in the composition of the spent medium. Altogether, our data indicate that inH. polymorphaat neutral pH the chronological lifespan invariably extends upon increasing the carbon source concentration.
authors.affiliation: Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, Systems Biology Centre for Metabolism and Ageing, University of Groningen, the Netherlands.
authors.forename: Adam
authors.initials: A
authors.lastname: Kawałek
authors.affiliation: Molecular Cell Biology, Groningen Biomolecular Sciences and Biotechnology Institute, Systems Biology Centre for Metabolism and Ageing, University of Groningen, the Netherlands.
authors.forename: Ida J
authors.initials: IJ
authors.lastname: van der Klei
keywords: Hansenula polymorpha; acidification; ageing; chronological lifespan; dietary restriction