Cardioprotection and lifespan extension by the natural polyamine spermidine

Eisenberg, Tobias and Abdellatif, Mahmoud and Schroeder, Sabrina and Primessnig, Uwe and Stekovic, Slaven and Pendl, Tobias and Harger, Alexandra and Schipke, Julia and Zimmermann, Andreas and Schmidt, Albrecht and Tong, Mingming and Ruckenstuhl, Christoph and Dammbrueck, Christopher and Gross, Angelina S and Herbst, Viktoria and Magnes, Christoph and Trausinger, Gert and Narath, Sophie and Meinitzer, Andreas and Hu, Zehan and Kirsch, Alexander and Eller, Kathrin and Carmona-Gutierrez, Didac and Büttner, Sabrina and Pietrocola, Federico and Knittelfelder, Oskar and Schrepfer, Emilie and Rockenfeller, Patrick and Simonini, Corinna and Rahn, Alexandros and Horsch, Marion and Moreth, Kristin and Beckers, Johannes and Fuchs, Helmut and Gailus-Durner, Valerie and Neff, Frauke and Janik, Dirk and Rathkolb, Birgit and Rozman, Jan and de Angelis, Martin Hrabe and Moustafa, Tarek and Haemmerle, Guenter and Mayr, Manuel and Willeit, Peter and von Frieling-Salewsky, Marion and Pieske, Burkert and Scorrano, Luca and Pieber, Thomas and Pechlaner, Raimund and Willeit, Johann and Sigrist, Stephan J and Linke, Wolfgang A and Mühlfeld, Christian and Sadoshima, Junichi and Dengjel, Joern and Kiechl, Stefan and Kroemer, Guido and Sedej, Simon and Madeo, Frank (2016) Cardioprotection and lifespan extension by the natural polyamine spermidine. Nature Medicine, (22). pp. 1428-1438. ISSN 1078-8956. (doi:https://doi.org/10.1038/nm.4222) (Full text available)

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http://doi.org/10.1038/nm.4222

Abstract

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. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.

Item Type: Article
Subjects: Q Science
Q Science > QP Physiology (Living systems)
Q Science > QP Physiology (Living systems) > QP506 Molecular biology
Q Science > QP Physiology (Living systems) > QP517 Biochemistry
R Medicine
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC667 Diseases of the circulatory (cardiovascular) system
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: P. Rockenfeller
Date Deposited: 18 Nov 2016 11:45 UTC
Last Modified: 16 May 2017 23:00 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/58741 (The current URI for this page, for reference purposes)
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