At neutral pH the chronological lifespan of Hansenulapolymorpha increases upon enhancing the carbon sourceconcentrations

摘要

Dietary restriction is generally assumed to increase the lifespan in most eukaryotes, including the simple model organism Saccharomyces 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 yeast Hansenula polymorpha using 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 that H. polymorpha acidifies 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 mediumacidification at these conditions, explaining the increased lifespan withincreasing glucose concentrations. Importantly, at neutral pH, the chronologicallifespan also decreases with a reduction in glycerol concentrations. We showthat for glycerol cultures this effect is related to acidification independentchanges in the composition of the spent medium. Altogether, our data indicatethat in H. polymorpha at neutral pH the chronological lifespaninvariably extends upon increasing the carbon source concentration.