Proteome maintenance is crucial to cellular health and viability, and is typically thought to be controlled in a cell-autonomous manner. However, recent evidence indicates that protein-folding defects can systemically activate proteostasis mechanisms through signalling pathways that coordinate stress responses among tissues. Coordination of ageing rates between tissues may also be mediated by systemic modulation of proteostasis. These findings suggest that proteome maintenance is a systemically regulated process, a discovery that may have important therapeutic implications.