Dissecting the effects of white willow Salix alba and salicin on yeast longevity
Objective Yeast cells are frequently used to model longevity and aging. Following the screening in yeast, chemical supplements and they are containing natural remedies could be pharmacologically assigned or repositioned as anti-cancerogenic and anti-aging substances. An extract from the white willow Salix alba is rich in salicin, a β-glucoside that contains D-glucose and salicylic acid. Salicin has a similar to aspirin anti-inflammatory effect. The extract also contains salicin-7-sulfate and physiologically active polyphenols.
Methods Protein phosphorylation and protein expression analyses.
Results The genetic yeast screen indicated that the anti-aging effect of Salix alba is linked to the PKH1/PKH2-dependent regulation of the Sch9 kinase. However, the phosphorylation of most PKH1/PKH2 targets, including YPK1/YPK2, was not affected in presence of S. alba. TORC1-dependent activation of Sch9 was inhibited, suggesting that similarly to aspirin or rapamycin, salicin acts to block TORC1 signaling either above or at the Tor1 level, respectively. Present in the S. alba extract salicin-7-sulfate could additionally decrease phosphorylation of Sch9 by blocking serine and threonine residues on the protein surface. Despite the decreased phosphorylation of Sch9, the phosphorylation of some other proteins was increased in the S. alba-treated cells. This occurred due to a kinase-swapping effect when the insufficient function of one kinase is compensated by other kinases with overlapping substrate specificity. Not only the phosphorylation but also the expression of numerous proteins was increased. Changes in the protein expression profiling were indicative of mild oxidative stress and activated UPR (unfolded protein response).
Conclusions Our findings suggest that S. alba has a complex effect on yeast cells: salicin-7-sulfate decreases protein phosphorylation, while salicin acts as an inhibitor of TORC1 signaling.