ABSTRACT Lysosomes are crucial for degradation and recycling of damaged proteins and cellular components. Therapeutic strategies enhancing lysosomal function are a promising approach for aging and age-related neurodegenerative diseases. Here, we show that an FDA approved drug sodium polystyrene sulfonate (SPS), used to reduce high blood potassium in humans, enhances lysosomal function both in C . elegans and in human neuronal cells. Enhanced lysosomal function following SPS treatment is accompanied by the suppression of proteotoxicity caused by expression of the neurotoxic peptides Aβ and TAU. Additionaly, treatment with SPS imparts health benefits as it significantly increases lifespan in C . elegans . Overall our work supports the potential use of SPS as a prospective geroprotective intervention. HIGHLIGHTS Sodium polystyrene sulfonate improves pH-dependent processing of lysosomal cargo, enhances proteotoxic stress resistance and extends lifespan in C. elegans Sodium polystyrene sulfonate boosts lysosomal function in human neuronal cells and reduces level of aggregation-associated phosphorylated-TAU

Potassium-chelating drug sodium polystyrene sulfonate enhances lysosomal function and suppresses proteotoxicity