Overexpression of polyphosphate polymerases and deletion of polyphosphate phosphatases shorten the replicative lifespan in yeast.

We previously found that overexpression of phosphate starvation-responsive genes by disrupting PHO80 led to a shortened replicative lifespan in yeast. To identify lifespan-related genes, we screened upregulated genes in the pho80Δ mutant and focused on the VTC genes, which encode the vacuolar polyphosphate (polyP) polymerase complex. VTC1/VTC2/VTC4 deletion restored the lifespan and intracellular polyP levels in pho80Δ. In the wild type, overexpression of VTC5 or a combination of the other VTCs caused high polyP accumulation and shortened lifespan. Similar phenotypes were caused by the deletion of polyP phosphatase genes-vacuolar PPN1 and cytosolic PPX1. The polyP-accumulating strains exhibited stress sensitivities. Thus, we demonstrated that polyP metabolic enzymes participate in replicative lifespan, and extreme polyP accumulation shortens the lifespan.