Abstract
Lysosome function is compromised during aging and in many disease states. Interventions that promote lysosomal activity and acidification are thus of prime interest as treatments for longevity and health. Intracellular pH can be controlled by the exchange of protons for inorganic ions, and in cells from microbes to man, when potassium is restricted in the growth medium, the cytoplasm becomes acidified. Here we use a yeast model to show that potassium limited-cells exhibit hallmarks of increased acidity in the vacuole, the analog of the lysosome, and live long by a mechanism that requires the vacuolar machinery. The emerging picture is one in which potassium restriction shores up vacuolar acidity and function, conferring health benefits early in life and extending viability into old age. Against the backdrop of well-studied protein and carbohydrate restrictions that extend lifespan and healthspan, our work establishes a novel pro-longevity paradigm of inorganic nutrient limitation.