Abstract

The yeast Saccharomyces cerevisiae is a beneficial organism for the discovery of genes, signaling pathways and chemical compounds that slow cellular and organismal aging in eukaryotes across phyla. As a first step towards uncovering novel aging-delaying chemical compounds, I conducted a screen of a library of plant extracts for those that can extend yeast chronological lifespan. My screen revealed six plant extracts that increase yeast chronological lifespan considerably more efficiently than any of the longevity-extending chemical compounds yet described. I show that each of the six plant extracts is a geroprotector which delays the onset and decreases the rate of yeast chronological aging by eliciting a hormetic stress response. Because the rate of aging in yeast is controlled by a network of integrated signaling pathways and protein kinases, I assessed how single-gene-deletion mutations eliminating each of these pathways and kinases affect the aging-delaying efficiencies of the six plant extracts. My findings imply that these extracts slow aging in the following ways: 1) plant extract 4 decreases the efficiency with which the pro-aging TORC1 pathway inhibits the anti-aging SNF1 pathway; 2) plant extract 5 mitigates two different branches of the pro-aging PKA pathway; 3) plant extract 6 coordinates processes that are not assimilated into the network of presently known signaling pathways/protein kinases; 4) plant extract 8 diminishes the inhibitory action of PKA on SNF1; 5) plant extract 12 intensifies the anti-aging protein kinase Rim15; and 6) plant extract 21 inhibits a form of the pro-aging protein kinase Sch9 that is activated by the pro-aging PKH1/2 pathway.