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

ABSTRACT: Hydrogen sulfide (H2S), a traditionally known cytotoxic gas, has been recently included in the gasotransmitters family. 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. Therefore, we investigated the effects of short H2S treatments at different time during yeast cell growth in the lifespan extension by using NaHS, a fast H2S-releasing donor. We show that short NaHS treatments at 4 days after inoculation extend yeast CLS while NaHS treatments earlier than 3 days after inoculation fail to do so. To reveal the mechanism of different consequences on yeast CLS of NaHS treatments at different times, we analyzed the transcriptome of Saccharomyces cerevisiae strain BY4742 with or without the early and late NaHS treatments. We found that the early and late NaHS treatments had similar effects on the expression of genes involved in pathways which are 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 such as genes involved in cell wall integrity. 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.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE160162 | GEO | 2023/10/02

REPOSITORIES: GEO

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Project description:The chronological lifespan (CLS) of Saccharomyces cerevisiae is defined as the number days that non-dividing cells remain viable, typically in stationary phase cultures or in water. CLS is extended by restricting glucose in the starting cultures, and is considered a form of caloric restriction (CR). Through a previous genetic screen our lab determined that deleting components of the de novo purine biosynthesis pathway also significantly increased CLS. Significant similarities in gene expression profiles between calorie restricted WT cells and a non-restricted ade4M-bM-^HM-^F mutant suggested the possibility of common gene expression biomarkers of all chronologically long lived cells that could also provide insights into general mechanisms of lifespan extension. We have identified additional growth conditions that extend CLS of WT cells, including supplementation of the media with isonicotinamide (INAM), a known sirtuin activator, or by supplementation with a concentrate collected from the expired media of a calorie restricted yeast culture, presumably due to an as yet unidentified longevity factor. Using these varied methods to extend CLS, we compared gene expression profiles in the aging cells (at day 8) to identify functionally relevant biomarkers of longevity. Nineteen genes were differentially regulated in all 4 of the long-lived populations relative to wild type. Of these 19 genes, viable haploid deletion mutants were available for 16 of them, and 12 were found to have a significant impact on CLS. Duplicate cultures were grown to saturation in SC media cultures, aged, and then harvested on day 8. The deletion mutant ade4M-bM-^HM-^F as well as WT cells treated with 25 mM isonicotinamide, calorie restricted (0.5% glucose), or treated with expired media concentrate from previously calorie restricted cultures. These 4 conditions were then compared to a wild-type (WT) strain. Total RNA was isolated and used for microarray hybridizations onto Affymetrix Yeast 2.0 Gene arrrays.

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

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