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Cardioprotection and lifespan extension by the natural polyamine spermidine

Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, …, Madeo F · 2016 · Nature Medicine · Atlas ID EIS2016

What this study shows

The mammalian follow-up to EIS2009 and the reason the spermidine branch matters for human health claims: oral spermidine extends mouse lifespan, reduces cardiac hypertrophy and preserves diastolic function, and the protection disappears in mice whose cardiomyocytes lack Atg5, which makes autophagy necessary rather than merely correlated. Boundary: the human part is a dietary questionnaire correlated with blood pressure and cardiovascular incidence, so it is observational and does not carry the causal claim the mouse data carry.

Abstract

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Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation.

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: Mice, Dahl salt-sensitive rats, plus a human dietary cohort); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type4 - Animal Study
Model systemMice, Dahl salt-sensitive rats, plus a human dietary cohort
JournalNature Medicine
Year2016
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1038/nm.4222 · PMID 27841876

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

  • Tobias Eisenberg first author · 2 studies in the Atlas

    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

  • Frank Madeo last author · 2 studies in the Atlas

    Established spermidine as a dietary compound that extends lifespan in yeast, worms, flies and mice, and showed that the effect depends on autophagy

  • Sabrina Schroeder 2 studies in the Atlas

    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

  • Christoph Ruckenstuhl 2 studies in the Atlas

    Yeast geneticist who works out how amino-acid restriction and vacuole acidity set lifespan

  • Christoph Magnes 2 studies in the Atlas

    Analytical chemist at Joanneum Research whose group contributed the mass-spectrometry measurements of polyamines in the Graz spermidine studies

More: 53 other authors
  • Didac Carmona-Gutierrez 2 studies in the Atlas

    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

  • Sabrina Büttner 2 studies in the Atlas

    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

  • Marion Horsch 2 studies in the Atlas

    Scientist at the Institute of Experimental Genetics, Helmholtz Munich, who has worked with Johannes Beckers on gene-expression studies of mouse models for the German Mouse Clinic

  • Kristin Moreth 2 studies in the Atlas

    Scientist at the German Mouse Clinic of Helmholtz Munich who contributed to its phenotyping of mouse models, including heart measurements

  • Johannes Beckers 2 studies in the Atlas

    Geneticist at Helmholtz Munich and the Technical University of Munich whose group at the Institute of Experimental Genetics runs gene-expression profiling for the German Mouse Clinic

  • Helmut Fuchs 2 studies in the Atlas

    Scientific and technical head of the German Mouse Clinic at Helmholtz Munich, the standardised many-organ testing platform for mouse models that Fuchs helped build

  • Valérie Gailus-Durner 2 studies in the Atlas

    Biochemist who co-founded the German Mouse Clinic at Helmholtz Munich and leads it as scientific head, running standardised testing of mouse models across many organ systems

  • Frauke Neff 2 studies in the Atlas

    First author of the study that separated what rapamycin does to lifespan from what it does to ageing itself

  • Birgit Rathkolb 2 studies in the Atlas

    Scientist at the German Mouse Clinic of Helmholtz Munich and the Gene Center of LMU Munich who contributes to the clinic's phenotyping of mouse models

  • Jan Rozman 2 studies in the Atlas

    Scientist who worked at the German Mouse Clinic of Helmholtz Munich on the standardised phenotyping of mouse models

  • Martin Hrabě de Angelis 1 study in the Atlas

    Mouse geneticist who directs large-scale phenotyping of mouse mutants and the German Mouse Clinic, a platform that tests how genes affect health and disease.

  • Tarek Moustafa 1 study in the Atlas

    Researcher in hepatic metabolism and bile acid signaling

  • Luca Scorrano 1 study in the Atlas

    Mitochondrial biologist known for showing how the shape of mitochondria and their inner folds (cristae) control energy production and cell death.

  • Junichi Sadoshima 2 studies in the Atlas

    Studies how mTOR, autophagy and mitophagy protect the heart under stress and in ageing, and contributed to the finding that spermidine protects the heart

  • Jörn Dengjel 3 studies in the Atlas

    Mass-spectrometry proteomics specialist in autophagy and protein homeostasis; co-author on the TBK1/ULK1–TFEB lysosomal stress pathway and on the spermidine lifespan and cardioprotection study.

No profile yet: Abdellatif M, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Dammbrueck C, Gross AS, Herbst V, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Janik D, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Muehlfeld C, Kiechl S, Sedej S

Related studies

More related studies

All 62 studies on Longevity

Topics

Cardiac agingLongevityAtg5SpermidineAutophagy

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.

InterventionOral spermidine supplementation (with cardiomyocyte Atg5 knockout as genetic test)
TargetAutophagy/mitophagy (Atg5-dependent)
ModelMouse (plus Dahl salt-sensitive rat model and a human dietary questionnaire cohort)
EffectSpermidine extends mouse lifespan and is cardioprotective in an autophagy-dependent manner; the human arm is observational dietary correlation only.

Cite this paper

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Eisenberg, T., Abdellatif, M., Schroeder, S., Primessnig, U., Stekovic, S., Pendl, T., Harger, A., Schipke, J., Zimmermann, A., Schmidt, A., Tong, M., Ruckenstuhl, C., Dammbrueck, C., Gross, A. S., Herbst, V., Magnes, C., Trausinger, G., Narath, S., Meinitzer, A., Hu, Z., Kirsch, A., Eller, K., Carmona-Gutierrez, D., Buettner, S., Pietrocola, F., Knittelfelder, O., Schrepfer, E., Rockenfeller, P., Simonini, C., Rahn, A., Horsch, M., Moreth, K., Beckers, J., Fuchs, H., Gailus-Durner, V., Neff, F., Janik, D., Rathkolb, B., Rozman, J., de Angelis, M. H., Moustafa, T., Haemmerle, G., Mayr, M., Willeit, P., von Frieling-Salewsky, M., Pieske, B., Scorrano, L., Pieber, T., Pechlaner, R., Willeit, J., Sigrist, S. J., Linke, W. A., Muehlfeld, C., Sadoshima, J., Dengjel, J., Kiechl, S., Sedej, S., & Madeo, F. (2016). Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine. https://doi.org/10.1038/nm.4222

@article{EIS2016,
  author       = {Eisenberg, T. and Abdellatif, M. and Schroeder, S. and Primessnig, U. and Stekovic, S. and Pendl, T. and Harger, A. and Schipke, J. and Zimmermann, A. and Schmidt, A. and Tong, M. and Ruckenstuhl, C. and Dammbrueck, C. and Gross, A. S. and Herbst, V. and Magnes, C. and Trausinger, G. and Narath, S. and Meinitzer, A. and Hu, Z. and Kirsch, A. and Eller, K. and Carmona-Gutierrez, D. and Buettner, S. and Pietrocola, F. and Knittelfelder, O. and Schrepfer, E. and Rockenfeller, P. and Simonini, C. and Rahn, A. and Horsch, M. and Moreth, K. and Beckers, J. and Fuchs, H. and Gailus-Durner, V. and Neff, F. and Janik, D. and Rathkolb, B. and Rozman, J. and de Angelis, M. H. and Moustafa, T. and Haemmerle, G. and Mayr, M. and Willeit, P. and von Frieling-Salewsky, M. and Pieske, B. and Scorrano, L. and Pieber, T. and Pechlaner, R. and Willeit, J. and Sigrist, S. J. and Linke, W. A. and Muehlfeld, C. and Sadoshima, J. and Dengjel, J. and Kiechl, S. and Sedej, S. and Madeo, F.},
  title        = {{Cardioprotection and lifespan extension by the natural polyamine spermidine}},
  journal      = {Nature Medicine},
  year         = {2016},
  doi          = {10.1038/nm.4222},
  note         = {PMID: 27841876},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper. 

Barton, O. (2026). Oliver's mTOR Atlas (record EIS2016) [Data set]. https://mtor-atlas.org/study/EIS2016/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_EIS2016,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record EIS2016},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/EIS2016/},
  doi          = {10.5281/zenodo.22059963}
}
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