A metabolic signature of long life in Caenorhabditis elegans

BackgroundMany Caenorhabditis elegans mutations increase longevity and much evidence suggests that they do so at least partly via changes in metabolism. However, up until now there has been no systematic investigation of how the metabolic networks of long-lived mutants differ from those of normal worms. Metabolomic technologies, that permit the analysis of many untargeted metabolites in parallel, now make this possible. Here we use one of these, 1H nuclear magnetic resonance spectroscopy, to investigate what makes long-lived worms metabolically distinctive.ResultsWe examined three classes of long-lived worms: dauer larvae, adult Insulin/IGF-1 signalling (IIS)-defective mutants, and a translation-defective mutant. Surprisingly, these ostensibly different long-lived worms share a common metabolic signature, dominated by shifts in carbohydrate and amino acid metabolism. In addition the dauer larvae, uniquely, had elevated levels of modified amino acids (hydroxyproline and phosphoserine). We interrogated existing gene expression data in order to integrate functional (metabolite-level) changes with transcriptional changes at a pathway level.ConclusionsThe observed metabolic responses could be explained to a large degree by upregulation of gluconeogenesis and the glyoxylate shunt as well as changes in amino acid catabolism. These responses point to new possible mechanisms of longevity assurance in worms. The metabolic changes observed in dauer larvae can be explained by the existence of high levels of autophagy leading to recycling of cellular components.See associated minireview: http://jbiol.com/content/9/1/7

• Publication year

  2010

• Venue

  BMC Biology

• Publication date

  2010-02-10

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/1741-7007-8-14PMID 20146810PMCID 2829508
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• [Caenorhabditis elegans].

  2020cited by this paper
• The cellular geometry of growth drives the amino acid economy of Caenorhabditis elegans

  2009cited by this paper
• A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance.

  2009cited by this paper
• Perceiving molecular evolution processes in Escherichia coli by comprehensive metabolite and gene expression profiling

  2008cited by this paper
• The Target of Rapamycin pathway antagonizes pha-4/FoxA to control development and aging.

  2008cited by this paper
• A comparative metabolomic study of NHR‐49 in Caenorhabditis elegans and PPAR‐α in the mouse

  2008cited by this paper
• Fat Metabolism Links Germline Stem Cells and Longevity in C. elegans

  2008cited by this paper
• The Caenorhabditis elegans K10C2.4 Gene Encodes a Member of the Fumarylacetoacetate Hydrolase Family

  2008cited by this paper
• NemaPath: online exploration of KEGG-based metabolic pathways for nematodes

  2008influential reference
• Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue

  2008cited by this paper
• Clustering of Genetically Defined Allele Classes in the Caenorhabditis elegans DAF-2 Insulin/IGF-1 Receptor

  2008influential reference
• Growth control of the eukaryote cell: a systems biology study in yeast

  2007cited by this paper
• Sex‐specific Effects of the DAF‐12 Steroid Receptor on Aging in Caenorhabditis elegans

  2007cited by this paper
• Ageing: When less is more

  2007cited by this paper
• Quantitative mass spectrometry identifies insulin signaling targets in C. elegans.

  2007influential reference
• Flexibility in energy metabolism supports hypoxia tolerance in Drosophila flight muscle: metabolomic and computational systems analysis

  2007cited by this paper
• KEGG for linking genomes to life and the environment

  2007influential reference
• Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts

  2007cited by this paper
• Metabotyping of Caenorhabditis elegans reveals latent phenotypes

  2007cited by this paper
• The C. elegans TGF-β Dauer Pathway Regulates Longevity via Insulin Signaling

  2007influential reference
• The C. elegans TGF-beta Dauer pathway regulates longevity via insulin signaling.

  2007influential reference
• eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans

  2007cited by this paper
• PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans

  2007cited by this paper
• Unravelling the moulting degradome: new opportunities for chemotherapy?

  2007cited by this paper
• Erratum to "Diapause-associated metabolic traits reiterated in long-lived daf-2 mutants in the nematode Caenorhabditis elegans" [Mech. Ageing Dev. 127 (5) (2006) 458-472].

  2006cited by this paper
• Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics.

  2006cited by this paper
• Branched-chain amino acids: enzyme and substrate regulation.

  2006cited by this paper
• Structural kinetic modeling of metabolic networks

  2006cited by this paper
• Retention and Loss of Amino Acid Biosynthetic Pathways Based on Analysis of Whole-Genome Sequences

  2006cited by this paper
• Long-term starvation and ageing induce AGE-1/PI 3-kinase-dependent translocation of DAF-16/FOXO to the cytoplasm

  2006cited by this paper
• Targeted profiling: quantitative analysis of 1H NMR metabolomics data.

  2006cited by this paper
• Diapause-associated metabolic traits reiterated in long-lived daf-2 mutants in the nematode Caenorhabditis elegans.

  2006influential reference
• Alternate metabolism during the dauer stage of the nematode Caenorhabditis elegans.

  2005cited by this paper
• Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress.

  2005cited by this paper
• From genomics to chemical genomics: new developments in KEGG

  2005influential reference
• New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen

  2005cited by this paper
• The plasticity of aging: insights from long-lived mutants.

  2005cited by this paper
• Combined Proteome and Metabolite-profiling Analyses Reveal Surprising Insights into Yeast Sulfur Metabolism*

  2005cited by this paper
• Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression.

  2005cited by this paper
• A systematic RNAi screen for longevity genes in C. elegans.

  2005cited by this paper
• The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span

  2004cited by this paper
• Discrimination Models Using Variance-Stabilizing Transformation of Metabolomic NMR Data

  2004cited by this paper
• Metabolomics and systems biology: making sense of the soup.

  2004cited by this paper
• The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans.

  2004cited by this paper
• Hormesis in Caenorhabditis elegans dauer-defective mutants

  2004cited by this paper
• BMC Biology

  2004influential reference
• Collagens, modifying enzymes and their mutations in humans, flies and worms.

  2004cited by this paper
• daf-28 encodes a C. elegans insulin superfamily member that is regulated by environmental cues and acts in the DAF-2 signaling pathway.

  2003cited by this paper
• Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan.

  2003cited by this paper
• Global analysis of dauer gene expression in Caenorhabditis elegans

  2003cited by this paper
• Choline phospholipid metabolism: A target in cancer cells?

  2003cited by this paper
• DAF-16 Target Genes That Control C. elegans Life-Span and Metabolism

  2003cited by this paper
• Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans

  2003influential reference
• Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF‐16

  2003cited by this paper
• Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in C. elegans

  2003cited by this paper
• Trehalose metabolism genes in Caenorhabditis elegans and filarial nematodes.

  2003cited by this paper
• Regulation of Hypoxic Death in C. elegans by the Insulin/IGF Receptor Homolog DAF-2

  2002influential reference
• Complementary Profiling of Gene Expression at the Transcriptome and Proteome Levels in Saccharomyces cerevisiae*S

  2002cited by this paper
• Regulation of gene expression, cellular localization, and in vivo function of Caenorhabditis elegans DNA topoisomerase I

  2001cited by this paper
• Transcriptome meets metabolome: hierarchical and metabolic regulation of the glycolytic pathway

  2001cited by this paper
• A functional genomics strategy that uses metabolome data to reveal the phenotype of silent mutations

  2001cited by this paper
• Early development of the otic placode.

  2001cited by this paper
• Regulation of DAF-2 receptor signaling by human insulin and ins-1, a member of the unusually large and diverse C. elegans insulin gene family.

  2001cited by this paper
• The Metabolic and Molecular Bases of Inherited Disease

  2001cited by this paper
• Metabolite profiling for plant functional genomics

  2000cited by this paper
• Functional genomic analysis of C. elegans chromosome I by systematic RNA interference

  2000cited by this paper
• KEGG: Kyoto Encyclopedia of Genes and Genomes

  2000influential reference
• Structure and function of the type 1 insulin-like growth factor receptor

  2000cited by this paper
• Correlation between Protein and mRNA Abundance in Yeast

  1999cited by this paper
• A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans.

  1999cited by this paper
• KEGG: Kyoto Encyclopedia of Genes and Genomes

  1999cited by this paper
• Thermotolerance in Saccharomyces cerevisiae: the Yin and Yang of trehalose.

  1998cited by this paper
• The genetics of caloric restriction in Caenorhabditis elegans.

  1998cited by this paper
• Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor.

  1998cited by this paper
• Two pleiotropic classes of daf-2 mutation affect larval arrest, adult behavior, reproduction and longevity in Caenorhabditis elegans.

  1998influential reference
• The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans

  1997cited by this paper
• daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans.

  1997cited by this paper
• The role of trehalose in the physiology of nematodes.

  1997cited by this paper
• A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans

  1996cited by this paper
• Genes that regulate both development and longevity in Caenorhabditis elegans.

  1995cited by this paper
• A C. elegans mutant that lives twice as long as wild type

  1993cited by this paper
• Maple syrup urine disease (branched chain ketoaciduria).

  1990cited by this paper
• [Genetics of Caenorhabditis elegans].

  1989cited by this paper
• Intermediary metabolism in the dauer larva of the nematode Caenorhabditis elegans— 1. Glycolysis, gluconeogenesis, oxidative phosphorylation and the tricarboxylic acid cycle

  1989cited by this paper
• Non-ageing developmental variant of Caenorhabditis elegans

  1976cited by this paper
• The genetics of Caenorhabditis elegans.

  1974cited by this paper
• The FASEB Journal • Research Communication Anabolic function of phenylalanine hydroxylase in

  year unknowncited by this paper

• Antioxidative Stress and Metabolic Regulation Effects of Black Goji Berry Anthocyanins from Aqueous Two-Phase Extraction in Caenorhabditis elegans

  2025cites this paper
• From Worms to Tumors: Conserved Strategies of Cellular Arrest and Survival Governing Dormancy.

  2025cites this paper
• Genetic mapping of lifespan and mitochondrialstress response in C. elegans

  2025cites this paper
• Rationale and design of the Dog Aging Project precision cohort: a multi-omic resource for longitudinal research in geroscience

  2025cites this paper
• Phenotypic and metabonomics studies of FMOs in C. elegans and their roles in lifespan extension

  2025influential citation
• Multi-Omics Integrative Analysis to Reveal the Impacts of Shewanella algae on the Development and Lifespan of Marine Nematode Litoditis marina

  2024cites this paper
• Self-DNA in Caenorhabditis elegans Affects the Production of Specific Metabolites: Evidence from LC-MS and Chemometric Studies

  2024cites this paper
• Catalytic activities of wild‐type C. elegans DAF‐2 kinase and dauer‐associated mutants

  2024cites this paper
• Unique tau‐ and synuclein‐dependent metabolic reprogramming in neurons distinct from normal aging

  2024cites this paper
• Sebacic acid as a potential age-related biomarker of liver aging: evidence linking mice and human.

  2023cites this paper
• Mid-IR imaging as a new tool to investigate waste heat production in the nematode C. elegans

  2023cites this paper
• Caenorhabditis elegans (C. elegans) sample preparation for metabolomics and lipidomics analysis – A review

  2023cites this paper
• The Native Microbiome Member Chryseobacterium sp. CHNTR56 MYb120 Induces Trehalose Production via a Shift in Central Carbon Metabolism during Early Life in C. elegans

  2023influential citation
• Metabolomic analysis reveals a differential adaptation process of the larval stages of Anisakis simplex to the host environment

  2023cites this paper
• Capillary electrophoresis-mass spectrometry as a tool for Caenorhabditis elegans metabolomics research

  2023cites this paper
• The metabolic contribution of SKN-1/Nrf2 to the lifespan of Caenorhabditis elegans

  2023cites this paper
• Age-associated anatomical and physiological alterations in Caenorhabditis elegans.

  2023cites this paper
• Age-Related Hormones Changes and Its Impact on Health Status and Lifespan

  2023cites this paper
• The unfolded protein response reverses the effects of glucose on lifespan in chemically-sterilized C. elegans

  2022cites this paper
• Untargeted Multimodal Metabolomics Investigation of the Haemonchus contortus Exsheathment Secretome

  2022cites this paper
• Accumulation of Glycogen and Upregulation of LEA-1 in C. elegans daf-2(e1370) Support Stress Resistance, Not Longevity

  2022cites this paper
• A Lactobacilli diet that confers MRSA resistance causes amino acid depletion and increased antioxidant levels in the C. elegans host

  2022cites this paper
• Isocitrate Dehydrogenase Alpha-1 Modulates Lifespan and Oxidative Stress Tolerance in Caenorhabditis elegans

  2022cites this paper
• Dichloroacetate and thiamine improve survival and mitochondrial stress in a C. elegans model of dihydrolipoamide dehydrogenase deficiency

  2022influential citation
• Radiation Hormesis to Improve the Quality of Adult Spodoptera litura (Fabr.)

  2022cites this paper
• The metabolite α-ketobutyrate increases health and life spans by activating AMPK

  2022cites this paper
• Quo Vadis Caenorhabditis elegans Metabolomics—A Review of Current Methods and Applications to Explore Metabolism in the Nematode

  2021cites this paper
• LSU Digital Commons LSU Digital Commons Metabolic restructuring during energy-limited states: Insights Metabolic restructuring during energy-limited states: Insights from Artemia franciscana embryos and other animals from Artemia franciscana embryos and other animals

  2021cites this paper
• Comparative Metabolomic Study of Drosophila Species with Different Lifespans

  2021cites this paper
• Identification of enzymes that have helminth-specific active sites and are required for Rhodoquinone-dependent metabolism as targets for new anthelmintics

  2021cites this paper
• A genetic model of methionine restriction extends Drosophila health- and lifespan

  2021cites this paper
• The Mitochondrial Prohibitin (PHB) Complex in C. elegans Metabolism and Ageing Regulation

  2021cites this paper
• Host and microbiota metabolic signals in aging and longevity

  2021cites this paper
• Knock-down of odr-3 and ife-2 additively extends lifespan and healthspan in C. elegans

  2021cites this paper
• Distinct metabolic alterations in different Caenorhabditis elegans mitochondrial mutants.

  2021cites this paper
• Kinetic characterization and thermostability of C. elegans cytoplasmic and mitochondrial malate dehydrogenases

  2021cites this paper
• Caloric restriction creates a metabolic pattern of chronological aging delay that in budding yeast differs from the metabolic design established by two other geroprotectors

  2021cites this paper
• The Metabolic Response to Infection With Wolbachia Implicates the Insulin/Insulin-Like-Growth Factor and Hypoxia Signaling Pathways in Drosophila melanogaster

  2021cites this paper
• Elevated Trehalose Levels in C. elegans daf-2 Mutants Increase Stress Resistance, Not Lifespan

  2021cites this paper
• A multimodal metabolomics approach to elucidate the trigger components 1 of rumen fluid for larval exsheathment in a model gastrointestinal parasitic

  2021cites this paper
• Downregulation of the tyrosine degradation pathway extends Drosophila lifespan

  2020cites this paper
• Regulation of the one carbon folate cycle as a shared metabolic signature of longevity

  2020cites this paper
• Metabolomics and lipidomics in C. elegans using a single sample preparation

  2020cites this paper
• A metabolic switch regulates the transition between growth and diapause in C. elegans

  2020cites this paper
• Transcriptomic and metabolomic profiling of long-lived growth hormone releasing hormone knock-out mice: evidence for altered mitochondrial function and amino acid metabolism

  2020cites this paper
• DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling

  2020influential citation
• Longevity effects of hispidol in Caenorhabditis elegans

  2020cites this paper
• Methionine transsulfuration pathway is upregulated in long-lived humans.

  2020cites this paper
• Targeting metabolic pathways for extension of lifespan and healthspan across multiple species.

  2020influential citation
• Gluconeogenesis and PEPCK are critical components of healthy aging and dietary restriction life extension

  2020cites this paper
• The aging hematopoietic stem cell niche

  2020cites this paper
• Metabolite Changes in an Estuarine Annelid Following Sublethal Exposure to a Mixture of Zinc and Boscalid

  2019cites this paper
• Profiling microRNAs through development of the parasitic nematode Haemonchus identifies nematode-specific miRNAs that suppress larval development

  2019cites this paper
• Of Mice, Whales, Jellyfish and Men: In Pursuit of Increased Longevity.

  2019cites this paper
• Metabolic Fingerprint of Acromegaly and Its Potential Usefulness in Clinical Practice

  2019cites this paper
• [De novo biosynthesis of glycerophospholipids and longevity].

  2019cites this paper
• 13C Labeling of Nematode Worms to Improve Metabolome Coverage by Heteronuclear Nuclear Magnetic Resonance Experiments

  2019cites this paper
• The metabolome as a biomarker of mortality risk in the common marmoset

  2019cites this paper
• Multi-Omics and Genome-Scale Modeling Reveal a Metabolic Shift During C. elegans Aging

  2019cites this paper
• Emerging Insights into the Metabolic Alterations in Aging Using Metabolomics

  2019cites this paper
• The PMK-3 (p38) Mitochondrial Retrograde Response Functions in Intestinal Cells to Extend Life via the ESCRT Machinery

  2019cites this paper
• Tryptophan metabolism is differently regulated between large and small dogs

  2019cites this paper
• Transcription factor NFYB-1 regulates mitochondrial function and promotes longevity induced by mitochondrial impairment

  2019cites this paper
• Emerging topics in C. elegans aging research: Transcriptional regulation, stress response and epigenetics

  2018cites this paper
• A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence

  2018cites this paper
• Similar post‐stress metabolic trajectories in young and old flies

  2018cites this paper
• 5‐Methoxyindole‐2‐carboxylic acid (MICA) suppresses A&bgr;‐mediated pathology in C. elegans

  2018cites this paper
• High-throughput sorting of eggs for synchronization of C. elegans in a microfluidic spiral chip.

  2018cites this paper
• Antiageing properties of Damaurone D in Caenorhabditis elegans

  2018cites this paper
• Dihydrolipoamide dehydrogenase suppression induces human tau phosphorylation by increasing whole body glucose levels in a C. elegans model of Alzheimer’s Disease

  2018cites this paper
• Preserved cardiac function by vinculin enhances glucose oxidation and extends health- and life-span

  2018cites this paper
• The induction of the fibroblast extracellular senescence metabolome is a dynamic process

  2018cites this paper
• BRCA1 and BARD1 mediate apoptotic resistance but not longevity upon mitochondrial stress in Caenorhabditis elegans

  2018cites this paper
• Modeling Meets Metabolomics—The WormJam Consensus Model as Basis for Metabolic Studies in the Model Organism Caenorhabditis elegans

  2018cites this paper
• Establishing a Connection between Alzheimer ' s Disease and Cellular Energy Transduction

  2018cites this paper
• The role of mitochondrial metabolism in health and disease

  2018cites this paper
• Establishing a Connection between Alzheimer's Disease and Cellular Energy Transduction

  2018cites this paper
• An insulin, AMPK, and steroid hormone-mediated metabolic switch regulates the transition between growth and diapause in C. elegans

  2018cites this paper
• The nematode Caenorhabditis elegans as a model for aging research

  2018cites this paper
• Mechanisms of Longevity Extension by Caloric Restriction and Lithocholic Acid in the Yeast Saccharomyces Cerevisiae

  2018cites this paper
• UvA-DARE ( Digital Academic Repository ) Metabolic control of aging in C . elegans

  2018cites this paper
• Preserved cardiac vinculin enhances extends health- and life-span

  2018cites this paper
• A window into extreme longevity; the circulating metabolomic signature of the naked mole-rat, a mammal that shows negligible senescence

  2018influential citation
• A nuclear role for the respiratory enzyme CLK-1 / COQ 7 in regulating mitochondrial stress responses and longevity

  2018cites this paper
• A sensitive mass spectrometry platform identifies metabolic changes of life history traits in C. elegans

  2017cites this paper
• Identification of key pathways and metabolic fingerprints of longevity in C. elegans

  2017cites this paper
• A multidimensional omics analysis of the DNA damage response in Caenorhabditis elegans

  2017influential citation
• Metabonomics approach to assessing the metabolism variation and gender gap of Drosophila melanogaster in aging process

  2017cites this paper
• Lipid Metabolism, Lipid Signalling and Longevity

  2017cites this paper
• Emerging Omics Approaches in Aging Research

  2017cites this paper
• Systems biology analysis using a genome-scale metabolic model shows that phosphine triggers global metabolic suppression in a resistant strain of C. elegans

  2017cites this paper
• Lifespan extension in Caenorhabditis elegans insulin/IGF-1 signalling mutants is supported by non-vertebrate physiological traits

  2017cites this paper
• Chapter 14 Lipid Metabolism , Lipid Signalling and Longevity

  2017cites this paper
• Proteomics and metabolomics in ageing research: from biomarkers to systems biology.

  2017cites this paper
• New views on the selection acting on genetic polymorphism in central metabolic genes

  2017cites this paper
• JAK/STAT and TGF-ß activation as potential adverse outcome pathway of TiO2NPs phototoxicity in Caenorhabditis elegans

  2017cites this paper
• daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival

  2017cites this paper
• Effect of dihydrolipoamide dehydrogenase (dld-1) on human tau phosphorylation in a C. elegans model of Alzheimer’s Disease

  2017cites this paper
• Micro-NMR elucidates altered metabolites in the Parkinson’s disease-related catp-6 genotype of Caenorhabditis elegans

  2017cites this paper
• Metabolomic signature associated with reproduction-regulated aging in Caenorhabditis elegans

  2017cites this paper