Hydrogen sulfide treatment at the late growth stage of Saccharomyces cerevisiae extends chronological lifespan

Previous studies demonstrated that lifelong treatment with a slow H₂S releasing donor extends yeast chronological lifespan (CLS), but it is not clear when the action of H₂S benefits to CLS during yeast growth. Here, we show that short H₂S treatments by using NaHS as a fast H₂S releasing donor at 96 hours after inoculation extended yeast CLS while NaHS treatments earlier than 72 hours after inoculation failed to do so. To reveal the mechanism, we analyzed the transcriptome of yeast cells with or without the early and late NaHS treatments. We found that both treatments had similar effects on pathways related to CLS regulation. Follow-up qPCR and ROS analyses suggest that altered expression of some antioxidant genes by the early NaHS treatments were not stable enough to benefit CLS. Moreover, transcriptome data also indicated that some genes were regulated differently by the early and late H₂S treatment. Specifically, we found that the expression of YPK2, a human SGK2 homolog and also a key regulator of the yeast cell wall synthesis, was significantly altered by the late NaHS treatment but not altered by the early NaHS treatment. Finally, the key role of YPK2 in CLS regulation by H₂S is revealed by CLS data showing that the late NaHS treatment did not enhance the CLS of a ypk2 knockout mutant. This study sheds light on the molecular mechanism of CLS extension induced by H₂S, and for the first time addresses the importance of H₂S treatment timing for lifespan extension.