Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hofer, SJ; Daskalaki, I; Bergmann, M; Friščić, J; Zimmermann, A; Mueller, MI; Abdellatif, M; Nicastro, R; Masser, S; Durand, S; Nartey, A; Waltenstorfer, M; Enzenhofer, S; Faimann, I; Gschiel, V; Bajaj, T; Niemeyer, C; Gkikas, I; Pein, L; Cerrato, G; Pan, H; Liang, Y; Tadic, J; Jerkovic, A; Aprahamian, F; Robbins, CE; Nirmalathasan, N; Habisch, H; Annerer, E; Dethloff, F; Stumpe, M; Grundler, F; Wilhelmi, de, Toledo, F; Heinz, DE; Koppold, DA; Rajput, Khokhar, A; Michalsen, A; Tripolt, NJ; Sourij, H; Pieber, TR; de, Cabo, R; McCormick, MA; Magnes, C; Kepp, O; Dengjel, J; Sigrist, SJ; Gassen, NC; Sedej, S; Madl, T; De, Virgilio, C; Stelzl, U; Hoffmann, MH; Eisenberg, T; Tavernarakis, N; Kroemer, G; Madeo, F.
Spermidine is essential for fasting-mediated autophagy and longevity.
Nat Cell Biol. 2024; 26(9):1571-1584
Doi: 10.1038/s41556-024-01468-x
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- Co-Autor*innen der Med Uni Graz
- Abdellatif Mahmoud
- Eisenberg Tobias
- Faimann Isabella
- Habisch Hansjörg
- Madl Tobias
- Sedej Simon
- Sourij Harald
- Tadic Jelena
- Tripolt Norbert
- Zimmermann Andreas
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Autophagy - drug effects
- Longevity - drug effects
- Spermidine - metabolism, pharmacology
- Animals - administration & dosage
- Fasting - administration & dosage
- Humans - administration & dosage
- Caenorhabditis elegans - metabolism
- Caloric Restriction - administration & dosage
- Peptide Initiation Factors - metabolism, genetics
- Eukaryotic Translation Initiation Factor 5A - administration & dosage
- Drosophila melanogaster - metabolism
- Saccharomyces cerevisiae - metabolism, genetics
- Mice - administration & dosage
- Male - administration & dosage
- Mice, Inbred C57BL - administration & dosage