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Induction of autophagy by spermidine promotes longevity
Open accessAbstract
Ageing results from complex genetically and epigenetically programmed processes that are elicited in part by noxious or stressful events that cause programmed cell death. Here, we report that administration of spermidine, a natural polyamine whose intracellular concentration declines during human ageing, markedly extended the lifespan of yeast, flies and worms, and human immune cells. In addition, spermidine administration potently inhibited oxidative stress in ageing mice. In ageing yeast, spermidine treatment triggered epigenetic deacetylation of histone H3 through inhibition of histone acetyltransferases (HAT), suppressing oxidative stress and necrosis. Conversely, depletion of endogenous polyamines led to hyperacetylation, generation of reactive oxygen species, early necrotic death and decreased lifespan. The altered acetylation status of the chromatin led to significant upregulation of various autophagy-related transcripts, triggering autophagy in yeast, flies, worms and human cells. Finally, we found that enhanced autophagy is crucial for polyamine-induced suppression of necrosis and enhanced longevity.
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In the citing paper
“recent studies with spermidine, a natural polyamine, have shown promising autophagy-dependent effects on yeast, flies and worms longevity and on mouse health-span (Eisenberg et al., 2009)”
From Protein Homeostasis and Aging: the importance of exquisite quality control (2011) · cites this paper as Eisenberg et al., 2009
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In the citing paper
“Spermidine, another macroautophagy inducer that, in contrast to rapamycin, has no immunosuppressive side-effects, also promotes longevity in yeast, flies and worms via the induction of autophagy (Eisenberg et al., 2009).”
From The Hallmarks of Aging (2013) · cites this paper as Eisenberg et al., 2009
In the citing paper
“In 2009, Eisenberg et al. identified the use of spermidine, a polyamine compound, to promote longevity, via autophagy, using PBMCs as model.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [190]
In the citing paper
“After 12 days, 50% of the cells survived after addition of spermidine.”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [190]
In the citing paper
“In fact, cell death, associated with membrane rupture, was indicative of necrosis (190).”
From Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention (2019) · cites this paper as [190]
In the citing paper
“and has been shown to be an effective antiaging agent [275,276,277].”
From The mitochondrial permeability transition: Nexus of aging, disease and longevity (2021) · cites this paper as [275]
In the citing paper
“Spermidine is a naturally occurring polyamine that triggers autophagy and, thereby, lifespan extension when supplemented in the food supply of yeast, flies and worms (Eisenberg et al., 2009).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Eisenberg et al., 2009
In the citing paper
“Both HDAC10 and spermidine are known to promote cellular survival through autophagy.”
From Histone deacetylase 10 structure and molecular function as a polyamine deacetylase (2017) · cites this paper as [36]
In the citing paper
“The polyamine spermidine is also a key factor in autophagy and increased levels of endogenous or exogenous spermidine induce autophagy and extend lifespan in a variety of cell types, including human immune cells3637.”
From Histone deacetylase 10 structure and molecular function as a polyamine deacetylase (2017) · cites this paper as [36]
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Metadata
- Authors
- Eisenberg, T., Knauer, H., Schauer, A., Büttner, S., Ruckenstuhl, C., Carmona-Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., Fussi, H., Deszcz, L., Hartl, R., Schraml, E., Criollo, A., Megalou, E., Weiskopf, D., Laun, P., Heeren, G., Breitenbach, M., Grubeck-Loebenstein, B., Herker, E., Fahrenkrog, B., Fröhlich, K.-U., Sinner, F., Tavernarakis, N., Minois, N., Kroemer, G., & Madeo, F.
- Affiliations
- University of Graz (AT)
- Joanneum Research (AT)
- Institute of Molecular Biotechnology (AT)
- BOKU University (AT)
- Université Paris-Sud (FR)
- Foundation for Research and Technology Hellas (GR)
- Austrian Academy of Sciences (AT)
- University of Salzburg (AT)
- Gladstone Institutes (US)
- University of Basel (CH)
- Corresponding author
- Kroemer, Guido
- Madeo, Frank
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2009-10-04
- Volume
- 11
- Issue
- 11
- Pages
- 1305-1314
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2045611938
- Cited by
- 1,680
- References
- 77
- Citations by year
- 2026: 115 · 2025: 116 · 2024: 99 · 2023: 118 · 2022: 125 · 2021: 129 · 2020: 121 · 2019: 104 · 2018: 124 · 2017: 76 · 2016: 93 · 2015: 74 · 2014: 91 · 2013: 99 · 2012: 69
- FWCI
- 19.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
- edoc (University of Basel) (submittedVersion)
- Oesterreichisches Musiklexikon online (Institut für kunst- und musikhistorische Forschungen der Österreichischen Akademie der Wissenschaften) (submittedVersion, other-oa)
- Austrian Biographical Dictionary (Austrian Academy of Sciences) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, other-oa)
- Zenodo (CERN European Organization for Nuclear Research) (cc-by)
- Funders
- European Commission (FP6 036894)
- Austrian Science Fund (S9304-B05, S9302-B05, S-9303-B05)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Polyamine Metabolism and Applications
- Keywords
- spermidine, polyamines, autophagy, longevity, lifespan extension, aging, histone H3 acetylation, histone acetyltransferase, oxidative stress, necrosis, reactive oxygen species, chromatin, immune cells, yeast, Drosophila, Caenorhabditis elegans, mice
- MeSH terms
- Acetylation, Adult, Animals, Autophagy, Drosophila melanogaster, Female, HeLa Cells, Histones, Humans, Hydrogen-Ion Concentration, Longevity, Male, Mice, Inbred C57BL, Necrosis, Saccharomyces cerevisiae, Spermidine, Caenorhabditis elegans, Mice
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