Potassium restriction phenocopies caloric restriction to extend chronological lifespan in yeast

Here, we show that extracellular potassium instead acts as a primary nutritional cue in Saccharomyces cerevisiae, exerting strong control over growth behaviour and chronological lifespan (CLS). The results indicate that in standard glucose (2%) medium, potassium restriction (PR) significantly extends the lifespan.

Notably, it exhibited calorie restriction (CR)-like phenotypes across all detection levels: both triggered synergistic downregulation of the HOG1 MAPK and TOR-Sch9 pathways, inducing highly overlapping transcriptional reprogramming, promoting vacuolar fusion into a single giant vacuole, strengthening cell wall and membrane structures, and reshaping metabolic networks, and comprehensively suppressing the production of aromatic amino acid metabolites and NAD⁺ degradation products while selectively accumulating protective purine and carnitine derivatives.