| Literature DB >> 27841876 |
Tobias Eisenberg1,2, Mahmoud Abdellatif3, Sabrina Schroeder1, Uwe Primessnig3,4, Slaven Stekovic1, Tobias Pendl1, Alexandra Harger1,5, Julia Schipke6,7, Andreas Zimmermann1, Albrecht Schmidt3, Mingming Tong8, Christoph Ruckenstuhl1, Christopher Dammbrueck1, Angelina S Gross1, Viktoria Herbst3, Christoph Magnes9, Gert Trausinger9, Sophie Narath9, Andreas Meinitzer10, Zehan Hu11,12, Alexander Kirsch13, Kathrin Eller13, Didac Carmona-Gutierrez1, Sabrina Büttner1,14, Federico Pietrocola15,16,17,18,19, Oskar Knittelfelder1, Emilie Schrepfer20,21, Patrick Rockenfeller1,22, Corinna Simonini3, Alexandros Rahn6, Marion Horsch23, Kristin Moreth23, Johannes Beckers23,24,25, Helmut Fuchs23, Valerie Gailus-Durner23, Frauke Neff23,26, Dirk Janik23,26, Birgit Rathkolb23,25,27, Jan Rozman23,25, Martin Hrabe de Angelis23,24,25, Tarek Moustafa1,5, Guenter Haemmerle1, Manuel Mayr28, Peter Willeit29,30, Marion von Frieling-Salewsky31, Burkert Pieske3,4,32, Luca Scorrano20,21, Thomas Pieber5,9, Raimund Pechlaner29, Johann Willeit29, Stephan J Sigrist33,34, Wolfgang A Linke31, Christian Mühlfeld6,7, Junichi Sadoshima8, Joern Dengjel11,12, Stefan Kiechl29, Guido Kroemer15,16,17,18,19,35,36, Simon Sedej2,3, Frank Madeo1,2.
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.Entities:
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Year: 2016 PMID： 27841876 PMCID： PMC5806691 DOI： 10.1038/nm.4222
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440