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

PROVIDER: PRJNA610525 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11243556_1.fastq.gz	Fastqsanger.gz
	SRR11243556_2.fastq.gz	Fastqsanger.gz
	SRR11243557_1.fastq.gz	Fastqsanger.gz
	SRR11243557_2.fastq.gz	Fastqsanger.gz
	SRR11243558_1.fastq.gz	Fastqsanger.gz

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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

Project description: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.

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Project description:Stress response of Methylococcus capsulatus str.Bath toward hydrogen sulfide (H2S) was investigated via physiological study and transcriptomic profiling. M. capsulatus (Bath) can grow and tolerate up to 0.75%vol H2S in headspace. Vast change in pH suggests biological relevant sulfide oxidation. Dozens of H2S-sensitive genes were identified from comparison of cell transcriptome in different H2S concentrations. Mc sulfide quinone reductase (SQR) and persulfide dioxygenase were found to be active during sulfide detoxification. Moreover, xoxF, a novel lanthanide(Ln)-dependent methanol dehydrogenase (MDH) was overexpressed in H2S while mxaF, a calcium-dependent MDH, was down-regulated, and such MDH switch phenomenon is also well known to be induced by addition of lanthanide via an as-yet-unknown mechanism. Activities in quorum sensing and RND efflux pump also suggest their role in sulfide detoxification, and might provide insight on the xoxF/mxaF switch mechanism.

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Project description:Hydrogen sulfide is a gasotransmitter with biological functions, including roles in antioxidant defenses, mitochondrial bioenergetics and cellular signaling via cysteine persulfidation. Several longevity-promoting interventions enhance endogenous hydrogen sulfide generation. However, whether enhanced hydrogen sulfide generation extends healthspan and lifespan in mammals remains unknown. Here, we investigated the in vivo effects of the non-enzymatic hydrogen sulfide generation promoted by natural diallyl sulforated compounds. Diallyl sulforated compounds extended lifespan and improved the main aspects of healthspan, including glucoregulation, locomotor function and neurocognition in wild type male mice across their lifespan. At histological and molecular levels, we observed reductions in hepatic lipid-droplet size, attenuation of transcriptional and proteomic signatures associated with mTOR and immune-related pathways, and increased cysteine persulfidation in proteins. In humans, greater protein persulfidation in individuals with polypathological conditions was associated with increased muscle strength and lower triglyceride levels, supporting its physiological relevance. Our findings uncover the potential of enhanced hydrogen sulfide generation to promote healthy aging.

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