The vacuole -- and its counterpart in humans and other organisms, the
lysosome -- has two main jobs: degrading proteins and storing molecular
building blocks for the cell. To perform those jobs, the interior of the
vacuole must be highly acidic.
Hughes and Gottschling found that the vacuole becomes less acidic
relatively early in the yeast cell's lifespan and, critically, that the
drop in acidity hinders the vacuole's ability to store certain
nutrients. This, in turn, disrupts the mitochondria's energy source,
causing them to break down. Conversely, when Hughes prevented the drop
in vacuolar acidity, the mitochondria's function and shape were
preserved and the yeast cells lived longer.
"Until now, the vacuole's role in breaking down proteins was thought to
be of primary importance. We were surprised to learn it was the storage
function, not protein degradation, that appears to cause mitochondrial
dysfunction in aging yeast cells," Hughes said.
The unexpected discovery prompted Hughes and Gottschling to investigate
the effects of calorie restriction, which is known to extend the
lifespan of yeast, worms, flies and mammals, on vacuolar acidity. They
found that calorie restriction -- that is, limiting the raw material
cells need -- delays aging at least in part by boosting the acidity of
"It’s cheap to maintain Lies and expensive to maintain Trvth."