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Lifespan and healthspan benefits of FW1256, a novel hydrogen sulfide donor compound, in C. elegans are independent from effects downstream of eat-2 mutation

ABSTRACT: It has been suggested that hydrogen sulfide (H2S) may play a pivotal role in mediating some of these caloric restriction (CR)-associated benefits. We therefore explored whether a novel slow-releasing H2S donor compound, FW1256, mimics CR and reproduces CR-associated effects in normal feeding Caenorhabditis elegans. Using transcriptomics analysis via RNA sequencing, we determined sets of differentially expressed genes (DEG) for FW1256-exposed wild-type C. elegans and eat-2 mutants, a genetic model of CR in C. elegans, relative to unexposed wild-type C. elegans. We found that, while FW1256 affects some of the same downstream genes as eat-2 mutation, global gene expression changes are dissimilar between FW1256-exposed C. elegans and eat-2 mutants, suggesting that novel slow-releasing H2S donor compound, FW1256, does not mimic CR at the transcriptional level.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE146412 | GEO | 2020/03/06

REPOSITORIES: GEO

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Project description:Analysis of gene expression in two long-lived daf-2 mutant (mutation in the insulin/IGF-1 receptor) and eat-2 mutant (caloric restriction model), comparison of gene expression profiles of two long-lived mutants provide novel insight into longevity Impaired insulin/IGF-1 signaling (IIS) pathway and caloric restriction (CR) are two well-established interventions to prolong lifespan in worm C. elegans. Although many studies using “-omics” approaches have gained informative knowledges on key longevity regulators in either IIS or CR models, few of those investigated the shared regulators between these two longevity interventions and integrated the messages from different –omics studies. In this study, we aimed to identify key pathways and metabolite fingerprints of longevity shared between the two interventions in worms using a multi-omics integration approach. We collected transcriptomics and metabolomics data from two long-lived mutant worm strains, i.e. daf-2 (impaired IIS pathway) and eat-2 (CR model) and compared with N2 strain. We detected many key pathways that were upregulated at the gene expression level in both long-lived mutants, such as defense response and lipid storage, while synthesis of macromolecules and developmental processes were downregulated at the transcript level. From our polar metabolite analysis, we discovered several shared metabolic features between the two long-lived mutants, including glycerol-3P, adenine, xanthine and AMP. In addition, we detected a lowered amino acid pool and two fatty acid species, C18:0 and C17:1, that behaved similarly in both long-lived mutants. After we integrated transcriptomics and metabolomics data based on the annotations in KEGG, our results highlighted a downregulation of pyrimidine metabolism and upregulation of purine metabolism in both long-lived mutants compared to N2 worms. Overall, our findings point towards the existence of shared metabolic pathways that are important for lifespan extension and provide novel insight of potential regulators and metabolic fingerprints for longevity.

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Lifespan and healthspan benefits of FW1256, a novel hydrogen sulfide donor compound, in C. elegans are independent from effects downstream of eat-2 mutation

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