Cyclin-dependent kinase Pho85p and its cyclins are involved in replicative lifespan through multiple pathways in yeast.

Lifespan is determined by genetic factors and influenced by environmental factors. Here, we find that the phosphate signal transduction (PHO) pathway is involved in the determination of replicative lifespan in budding yeast. Extracellular phosphate does not affect the lifespan. However, deletion of PHO80 (cyclin) and PHO85 (cyclin-dependent kinase) genes, that is, negative regulators of the PHO pathway, shortens the lifespan, which is restored by further deletion of PHO4 (transcriptional activator). Four of the other nine Pho85p cyclin genes are also required to maintain normal lifespan. The short-lived mutants show a metabolic profile that is similar to strains with normal lifespan. Thus, Pho85p kinase genetically determines replicative lifespan in combination with relevant cyclins. Our findings uncover novel cellular signals in longevity regulation.