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Transcriptomic profiling of human senescent cells in the setting of curcumin intervention

ABSTRACT: Aging and age-relataed pathologies can be delayed by specifically targeting the senescence-associated secretory phenotype (SASP), a hallmark feature of senescent cells. Achieving the goal using small molecules would have a tremendous impact on the quality of lifespan and burden of age-related chronic diseases. We report the potential of curcumin, a polyphenol constituent (up to ∼5%) of the traditional medicine known as turmeric, in targeting senescent cells via induction of programmed cell death. This study demonstrates the impact of curcumin as a medicinal compound on the expression profile of senescent cells and provides a strong rationale for its future application in geriatric medicine.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156472 | GEO | 2022/12/31

REPOSITORIES: GEO

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Project description:Curcumin is a polyphenolic compound extracted from the turmeric plant (Curcuma longa) and has been extensively studied for its anti-inflammatory and anti-proliferative properties. The safety and effectiveness of curcumin have been thoroughly proven. However, the mechanisms underlying the treatment of osteoarthritis remain unclear. This study aimed to reveal the potential mechanism of curcumin in the treatment of osteoarthritis through metabolomics and transcriptomics. First, we verified the effect of curcumin on inflammatory factors in human articular chondrocytes. Secondly, we used cellular metabolomics to explore the cellular metabolic mechanism of curcumin against osteoarthritis. Third, we evaluated differences in gene expression in human articular chondrocytes by transcriptomics. Finally, to evaluate essential targets and elucidate the underlying mechanisms of curcumin in the treatment of osteoarthritis, we performed a screen for proteins in pathways shared by metabolomics and transcriptomics. Our results showed that curcumin significantly reduced the levels of inflammatory markers, such as IL-β, IL-6, and TNF-α, in human articular chondrocytes. Cellular metabolomics identified 106 differential metabolites, including beta-aminopropionitrile, 3-amino-2-piperidone, pyrrole-2-carboxaldehyde, and various other components. Transcriptome analysis yielded 1050 differential mRNAs. Enrichment analysis showed that differential metabolites and mRNA were significantly enriched in 7 pathways including glycine, serine, and threonine metabolism; interconversion of pentose and glucuronic acid; glycerolipid metabolism; histidine metabolism; mucin type O-glycan biosynthesis; phosphoinositide metabolism; and cysteine and methionine metabolism. A total of 23 key targets were identified to be involved in these pathways. We speculate that curcumin may alleviate osteoarthritis by targeting key proteins involved in glycine, serine, and threonine metabolism, inhibiting pyruvate production, and regulating glycolysis.

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Transcriptomic profiling of human senescent cells in the setting of curcumin intervention

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