Spermidine is essential for fasting-mediated autophagy and longevity
Year: 2024
Type: article
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.
Source: Nature Cell Biology
Authors: Sebastian J. Hofer, Ioanna Daskalaki, Martina Bergmann, Jasna Friščić, Andreas Zimmermann, Melanie I. Mueller, Mahmoud Abdellatif, Raffaele Nicastro, Sarah Masser, Sylvère Durand, Alexander Nartey, Mara Waltenstorfer, Sarah Enzenhofer, Isabella Faimann, Verena Gschiel, Thomas Bajaj, Christine Niemeyer, Ilias Gkikas, Lukas Pein, Giulia Cerrato, Hui Pan, YongTian Liang, Jelena Tadic, Andrea Jerkovic, Fanny Aprahamian, Christine E. Robbins, Nitharsshini Nirmalathasan, Hansjörg Habisch, Elisabeth Annerer, Frederik Dethloff, Michael Stumpe, Franziska Grundler, Françoise Wilhelmi de Toledo, Daniel E. Heinz, Daniela A. Koppold, Anika Rajput Khokhar, Andreas Michalsen, Norbert J. Tripolt, Harald Sourij, Thomas R. Pieber, Rafael de Cabo, Mark A. McCormick, Christoph Magnes, Oliver Kepp, Joern Dengjel, Stephan J. Sigrist, Nils C. Gassen, Simon Sedej, Tobias Madl, Claudio De Virgilio, Ulrich Stelzl, Markus H. Hoffmann, Tobias Eisenberg, Nektarios Tavernarakis, Guido Kroemer, Frank Madeo
Institutions: Inserm, University of Graz, Institut Universitaire de France, Université Paris Cité, Université Paris-Saclay, Institut Gustave Roussy, Sorbonne Université, Centre de Recherche des Cordeliers, Nawi Graz, BioTechMed-Graz, University of Crete, FORTH Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, University of Lübeck, Medical University of Graz, University of Fribourg, University Hospital Bonn, NeuroCure Cluster of Excellence, Freie Universität Berlin, University of New Mexico Health Sciences Center, Max Planck Institute for Biology of Ageing, Buchinger Wilhelmi, Humboldt-Universität zu Berlin, Immanuel Krankenhaus, Charité – Universitätsmedizin Berlin, Joanneum Research, National Institutes of Health, National Institute on Aging, University of Maribor, Assistance Publique – Hôpitaux de Paris, Hôpital Européen Georges-Pompidou
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,290
Awards: Next-generation phenotypic screening for oncological applications, Amino acid signaling and growth control in yeast, G2129363707, EXC 2167: Präzisionsmedizin für Chronische Entzündungserkrankungen (PMI), G3832214737, Stimulus- and time-dependent protein dynamics in autophagy analyzed by quantitative mass spectrometry, G5324368231, Amino Acid Signaling and Growth Control in Yeast, Université de Paris, G8690818240, Autophagy, Inflammation and Metabolism (AIM) in Disease Center - Phase 2.
OpenAlex ID: W4401428136