Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>

Background: Aging and age-related diseases are closely linked to an imbalance in energy supply and demand, a condition that can potentially be mitigated through various interventions, including the use of naturally occurring molecules. Norathyriol (NL), a tetrahydroxyxanthone compound, is prevalent...

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Main Authors: Hong-Jia Zhang, Hai-Quan Lan, Meng-Ying Wang, Cai-Feng Wang, Lu-Gang Wei, Chen Xu
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Metabolites
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Online Access:https://www.mdpi.com/2218-1989/14/12/716
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author Hong-Jia Zhang
Hai-Quan Lan
Meng-Ying Wang
Cai-Feng Wang
Lu-Gang Wei
Chen Xu
author_facet Hong-Jia Zhang
Hai-Quan Lan
Meng-Ying Wang
Cai-Feng Wang
Lu-Gang Wei
Chen Xu
author_sort Hong-Jia Zhang
collection DOAJ
description Background: Aging and age-related diseases are closely linked to an imbalance in energy supply and demand, a condition that can potentially be mitigated through various interventions, including the use of naturally occurring molecules. Norathyriol (NL), a tetrahydroxyxanthone compound, is prevalent in mango fruit and medicinal plants. While studies have indicated that NL may influence metabolism, its effects on aging have not been extensively explored. Methods: We conducted lifespan analysis and measured lipofuscin accumulation in <i>C. elegans</i> model to evaluate the effects of NL on aging. Additionally, we identified differentially expressed genes (DEGs) through comprehensive RNA-sequencing (RNA-seq) analysis and performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGGs) pathway analyses to elucidate the molecular mechanisms underlying NL’s effects. Results: Our study demonstrated that NL at 50 μM extends the lifespan by 15.9% and reduces lipofuscin accumulation in <i>C. elegans</i> without impacting their feeding capabilities. A total of 928 DEGs were identified in NL-treated worms. The analysis of DEGs indicated that NL’s longevity-promoting effects might be due to its regulation of gene expression in lipid metabolism and immune response pathways. Furthermore, the insulin/insulin-like growth factor (IGF)-1 and target of rapamycin (TOR) signaling pathways were implicated in the lifespan-extending effect of NL. Conclusions: These findings broaden the bioactivity profile of polyphenols and highlight the need for further investigation into the therapeutic potential of NL in combating age-related diseases.
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spelling doaj-art-d84ebf58eaab48ce8b0a3cd1e97aa2952025-08-20T02:00:43ZengMDPI AGMetabolites2218-19892024-12-01141271610.3390/metabo14120716Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>Hong-Jia Zhang0Hai-Quan Lan1Meng-Ying Wang2Cai-Feng Wang3Lu-Gang Wei4Chen Xu5State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Materials-Oriented Chemical Engineering, College of Chemical Engineering, Nanjing Tech University, Nanjing 210009, ChinaState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, ChinaBackground: Aging and age-related diseases are closely linked to an imbalance in energy supply and demand, a condition that can potentially be mitigated through various interventions, including the use of naturally occurring molecules. Norathyriol (NL), a tetrahydroxyxanthone compound, is prevalent in mango fruit and medicinal plants. While studies have indicated that NL may influence metabolism, its effects on aging have not been extensively explored. Methods: We conducted lifespan analysis and measured lipofuscin accumulation in <i>C. elegans</i> model to evaluate the effects of NL on aging. Additionally, we identified differentially expressed genes (DEGs) through comprehensive RNA-sequencing (RNA-seq) analysis and performed gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGGs) pathway analyses to elucidate the molecular mechanisms underlying NL’s effects. Results: Our study demonstrated that NL at 50 μM extends the lifespan by 15.9% and reduces lipofuscin accumulation in <i>C. elegans</i> without impacting their feeding capabilities. A total of 928 DEGs were identified in NL-treated worms. The analysis of DEGs indicated that NL’s longevity-promoting effects might be due to its regulation of gene expression in lipid metabolism and immune response pathways. Furthermore, the insulin/insulin-like growth factor (IGF)-1 and target of rapamycin (TOR) signaling pathways were implicated in the lifespan-extending effect of NL. Conclusions: These findings broaden the bioactivity profile of polyphenols and highlight the need for further investigation into the therapeutic potential of NL in combating age-related diseases.https://www.mdpi.com/2218-1989/14/12/716norathyriolaging<i>C. elegans</i>lipid metabolismtranscriptome analysis
spellingShingle Hong-Jia Zhang
Hai-Quan Lan
Meng-Ying Wang
Cai-Feng Wang
Lu-Gang Wei
Chen Xu
Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>
Metabolites
norathyriol
aging
<i>C. elegans</i>
lipid metabolism
transcriptome analysis
title Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>
title_full Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>
title_fullStr Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>
title_full_unstemmed Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>
title_short Transcriptome Analysis Reveals Norathyriol Prolongs the Lifespan via Regulating Metabolism in <i>C. elegans</i>
title_sort transcriptome analysis reveals norathyriol prolongs the lifespan via regulating metabolism in i c elegans i
topic norathyriol
aging
<i>C. elegans</i>
lipid metabolism
transcriptome analysis
url https://www.mdpi.com/2218-1989/14/12/716
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