Induction of autophagy by spermidine promotes longevity
What this study shows
The opening paper of the caloric-restriction-mimetic branch: a natural polyamine whose level falls with human age extends lifespan in yeast, flies, worms and human immune cells, and the effect depends on autophagy. In ageing yeast this works through inhibition of histone acetyltransferases, which raises autophagy gene expression. The paper did not measure mTOR, so whether this route bypasses mTOR is not tested here. Boundary: no mammalian lifespan data in this paper.
Abstract
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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.
Read the full abstract on PubMed →At a glance
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| Evidence type | A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Yeast, Drosophila, C. elegans, mice, human immune cells); the code names the system studied -- animal work can be rigorous and still not be human data. |
| Study type | 4 - Animal Study |
| Model system | Yeast, Drosophila, C. elegans, mice, human immune cells |
| Journal | Nature Cell Biology |
| Year | 2009 |
| Peer reviewed | Yes |
| Record last updated | 2026-10-01 |
| Source | DOI 10.1038/ncb1975 · PMID 19801973 |
Where this study fits
How this study connects to the pathway map, open questions, people and other studies in the Atlas.
Open question
Mechanism-to-outcome gap · H4
Is autophagy actually REQUIRED for the mammalian lifespan benefit?Cited there as evidence. Evidence stands at: Lifespan in mice (sufficiency only).
People in the Atlas
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Showed as first author that the dietary polyamine spermidine extends lifespan by inducing autophagy, and later that it protects the heart in an autophagy-dependent way
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Established spermidine as a dietary compound that extends lifespan in yeast, worms, flies and mice, and showed that the effect depends on autophagy
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Studies how organelles communicate inside cells and how that communication breaks down with age, and contributed to the Graz studies showing that spermidine extends lifespan by inducing autophagy
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Yeast geneticist who works out how amino-acid restriction and vacuole acidity set lifespan
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Studies how cell death and autophagy shape ageing at the University of Graz, and contributed to the studies showing that spermidine extends lifespan through autophagy
More: 24 other authors
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Researcher in Frank Madeo's group at Graz who has contributed to the spermidine studies from the first yeast longevity experiments to work in mice
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Analytical chemist at Joanneum Research whose group contributed the mass-spectrometry measurements of polyamines in the Graz spermidine studies
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Geneticist who uses the roundworm C. elegans to study how ageing, neurodegeneration, necrotic cell death, autophagy and protein turnover are controlled
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Cell biologist known for work on programmed cell death, mitochondria and autophagy, and for linking autophagy to ageing and cancer immunity.
No profile yet: Knauer H, Schauer A, Ring J, 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, Froehlich KU, Sinner F, Minois N
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Topics
Extracted findings
These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.
| Intervention | spermidine administration; depletion of endogenous polyamines; autophagy gene disruption |
| Target | autophagy, via histone acetyltransferase inhibition and histone H3 deacetylation |
| Model | yeast, Drosophila, C. elegans, human immune cells, and ageing mice for oxidative stress only |
| Effect | Spermidine extended lifespan in yeast, flies and worms and raised autophagy, and the longevity benefit was lost when autophagy was disabled. |
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