ArticleNature cell biology2024
Spermidine is essential for fasting-mediated autophagy and longevity.
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Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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111citing papers in PubMed
–field-weighted citation impact
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Who cites it
111 citing papers in PubMed.
- Longitudinal association of dietary spermidine with hepatic function indexes and cardiometabolic traits in older adults with metabolic syndrome.European journal of nutrition · 2026Trial
- Intermittent fasting and a no-sugar diet for Long COVID symptoms: a randomized crossover trial.Scientific reports · 2025Trial
- Association of serum spermidine level with vascular calcification in peritoneal dialysis patients.Renal failure · 2026Article
- A Mechanism-Based Framework for Anti-Aging Strategies: From Metabolic Regulation to Senotherapy and Stem Cell-Based Interventions.Aging cell · 2026Review
- Polyamines, cardiorespiratory fitness, body composition, and mitochondrial function in older patients with coronary artery disease.European heart journal open · 2026Article
- Temporal Proteomic Profiling Reveals Tissue-Specific and Coordinated Metabolic Reprogramming in Skeletal Muscle and Liver during Prolonged Fasting.Proteomics · 2026Article
- Polyamine metabolic enzyme SAT1 remodels the neuronal transcriptome and rescues α-synuclein toxicity in Drosophila.Amino acids · 2026Article
- Spermidine in Colorectal cancer: friend or foe?Amino acids · 2026Review
- Comprehensive transcriptomic profiling reveals impaired polyamine metabolism as a contributor to age-related muscle decline.iScience · 2026Article
- Phosphorylation of OTUB1 promotes autophagy initiation under starvation.Nature communications · 2026Article
- ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.Nature communications · 2026Article
- Natural Bioactive Compounds Targeting Key Hallmarks of Aging: Functional Food Potential of Spermidine, Fisetin, Berberine, and Urolithin A.Nutrients · 2026Review
- Established and emerging roles of lysosomal dysfunction in cardiac aging.Nature cardiovascular research · 2026Review
- Article
- Gene- and Isoform-Level Responses to Extreme Acidic pH Stress in an Emerging Marine Invertebrate Model OrganismAntioxidants (Basel, Switzerland) · 2026Article
- Polyamines in CNS malignancies: positively charged culprits in the hijacking of neural and immune signaling pathways.Amino acids · 2026Review
- Article
- HKDC1-mediated polyamine rewiring drives lenvatinib resistance and immune escape in hepatocellular carcinoma.Clinical and molecular hepatology · 2026Article
- Cancer cells adopt unprecedented strategies to produce a molecule that protects them from iron-dependent death.Nature · 2026Article
- Combined Time-Restricted Feeding and Physical Exercise Attenuate ER Stress and Improve Liver Inflammation and Collagen Deposition in Aged Mice.Cell biochemistry and function · 2026Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
56 authors.
Sebastian J HoferInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0002-0756-0014
Ioanna DaskalakiInstitute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Greece.
Martina BergmannInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
Jasna FriščićDepartment of Dermatology, Allergy and Venerology, University of Lübeck, Lübeck, Germany.
Andreas ZimmermannInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0003-2249-944X
Melanie I MuellerInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0002-7472-2677
Mahmoud AbdellatifBioTechMed Graz, Graz, Austria.ORCID 0000-0002-5042-9054
Raffaele NicastroDepartment of Biology, University of Fribourg, Fribourg, Switzerland.ORCID 0000-0002-5420-2228
Sarah MasserBioTechMed Graz, Graz, Austria.ORCID 0000-0002-5195-0650
Sylvère DurandCentre de Recherche des Cordeliers, Équipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
Alexander NarteyInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
Mara WaltenstorferInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0001-7541-8338
Sarah EnzenhoferInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0009-0006-7474-5226
Isabella FaimannInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
Verena GschielInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0002-1090-9010
Thomas BajajNeurohomeostasis Research Group, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
Christine NiemeyerNeurohomeostasis Research Group, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
Ilias GkikasInstitute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Greece.
Lukas PeinInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.
Giulia CerratoCentre de Recherche des Cordeliers, Équipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
Hui PanCentre de Recherche des Cordeliers, Équipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
YongTian LiangInstitute for Biology and Genetics, Freie Universität Berlin, Berlin, Germany.ORCID 0000-0002-5802-1045
Jelena TadicInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0001-6232-5378
Andrea JerkovicInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0002-0442-712X
Fanny AprahamianCentre de Recherche des Cordeliers, Équipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
Christine E RobbinsDepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Nitharsshini NirmalathasanCentre de Recherche des Cordeliers, Équipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.
Hansjörg HabischResearch Unit Integrative Structural Biology, Otto Loewi Research Center, Medicinal Chemistry, Medical University of Graz, Graz, Austria.ORCID 0000-0001-5537-506X
Elisabeth AnnererInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.
Frederik DethloffMax Planck Institute for Biology of Ageing, Cologne, Germany.
Michael StumpeDepartment of Biology, University of Fribourg, Fribourg, Switzerland.
Franziska GrundlerBuchinger Wilhelmi Clinic, Überlingen, Germany.
Françoise Wilhelmi de ToledoBuchinger Wilhelmi Clinic, Überlingen, Germany.
Daniel E HeinzNeurohomeostasis Research Group, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
Daniela A KoppoldInstitute of Social Medicine, Epidemiology and Health Economics, corporate member of Freie Universität Berlin and Humboldt-Universität, Charité-Universitätsmedizin, Berlin, Germany.
Anika Rajput KhokharInstitute of Social Medicine, Epidemiology and Health Economics, corporate member of Freie Universität Berlin and Humboldt-Universität, Charité-Universitätsmedizin, Berlin, Germany.ORCID 0000-0002-0135-9643
Andreas MichalsenInstitute of Social Medicine, Epidemiology and Health Economics, corporate member of Freie Universität Berlin and Humboldt-Universität, Charité-Universitätsmedizin, Berlin, Germany.
Norbert J TripoltInterdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
Harald SourijInterdisciplinary Metabolic Medicine Trials Unit, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria.
Thomas R PieberBioTechMed Graz, Graz, Austria.
Rafael de CaboExperimental Gerontology Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.ORCID 0000-0002-3354-2442
Mark A McCormickDepartment of Biochemistry and Molecular Biology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Christoph MagnesHEALTH - Institute for Biomedical Research and Technologies, Joanneum Research Forschungsgesellschaft, Graz, Austria.ORCID 0000-0002-5153-7444
Oliver KeppCentre de Recherche des Cordeliers, Équipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France.ORCID 0000-0002-6081-9558
Joern DengjelDepartment of Biology, University of Fribourg, Fribourg, Switzerland.ORCID 0000-0002-9453-4614
Stephan J SigristInstitute for Biology and Genetics, Freie Universität Berlin, Berlin, Germany.ORCID 0000-0002-1698-5815
Nils C GassenNeurohomeostasis Research Group, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.ORCID 0000-0002-4265-3398
Simon SedejBioTechMed Graz, Graz, Austria.ORCID 0000-0002-4419-6821
Tobias MadlBioTechMed Graz, Graz, Austria.ORCID 0000-0002-9725-5231
Claudio De VirgilioDepartment of Biology, University of Fribourg, Fribourg, Switzerland.ORCID 0000-0001-8826-4323
Ulrich StelzlField of Excellence BioHealth, University of Graz, Graz, Austria.ORCID 0000-0003-2500-3585
Markus H HoffmannDepartment of Dermatology, Allergy and Venerology, University of Lübeck, Lübeck, Germany.
Tobias EisenbergInstitute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria.ORCID 0000-0003-3559-1130
Nektarios Tavernarakis *Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Greece. tavernarakis@imbb.forth.gr.ORCID 0000-0002-5253-1466
Guido Kroemer *Centre de Recherche des Cordeliers, Équipe Labellisée par la Ligue Contre le Cancer, Université de Paris Cité, Sorbonne Université, Inserm U1138, Institut Universitaire de France, Paris, France. kroemer@orange.fr.ORCID 0000-0002-9334-4405
Frank Madeo *Institute of Molecular Biosciences, NAWI Graz, University of Graz, Graz, Austria. frank.madeo@uni-graz.at.ORCID 0000-0002-5070-1329
Funding
Unfolded Protein Response and Autophagy in T Helper Cell Effector FunctionP20GM121176 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI VOJO P DERETIC · 2017 to 2026
$24.9MAustrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) DOC-50Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) F3012Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) I3301-MINOTAURAustrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P27637-B28Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P27893Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P29203Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P29262Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) P33957Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) TAI6021000Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung) W1226Austrian Science Fund FWF I 3792Austrian Science Fund FWF P 27893Austrian Science Fund FWF P 29203Austrian Science Fund FWF P 29262Austrian Science Fund FWF P 33957Austrian Science Fund FWF TAI 602Austrian Science Fund FWF W 1226Deutsche Forschungsgemeinschaft (German Research Foundation) 672032Deutsche Forschungsgemeinschaft (German Research Foundation) EXC2167-390884018Deutsche Forschungsgemeinschaft (German Research Foundation) FOR2886/2-TP08Deutsche Forschungsgemeinschaft (German Research Foundation) SI 849/14-1 (Project-ID 445178831)Karl-Franzens-Universität Graz (University of Graz) Field of Excellence BioHealthMedizinische Universität Graz (Medical University of Graz) Flagship project VASC-HEALTHNIGMS NIH HHS P20 GM121176Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_166474/184671Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_184781
Abstract
Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.
Indexed as
AutophagyCaenorhabditis elegansCaloric RestrictionFastingLongevitySpermidineAnimalsDrosophila melanogasterEukaryotic Translation Initiation Factor 5AHumansMaleMiceMice, Inbred C57BLPeptide Initiation FactorsSaccharomyces cerevisiaeEukaryotic Translation Initiation Factor 5APeptide Initiation FactorsSpermidine
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.