1. Cardioprotection and lifespan extension by the natural polyamine spermidine
- Author
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Burkert Pieske, Uwe Primessnig, Johannes Beckers, Tobias Pendl, Thomas R. Pieber, Peter Willeit, Andreas Meinitzer, Luca Scorrano, Johann Willeit, Wolfgang A. Linke, Sophie H. Narath, Birgit Rathkolb, Alexander H. Kirsch, Helmut Fuchs, Jan Rozman, Mingming Tong, Christopher Dammbrueck, Dirk Janik, Tobias Eisenberg, Marion Horsch, Gert Trausinger, Andreas Zimmermann, Slaven Stekovic, Christian Mühlfeld, Sabrina Schroeder, Stefan Kiechl, Valerie Gailus-Durner, Patrick Rockenfeller, Didac Carmona-Gutierrez, Tarek Moustafa, Viktoria Herbst, Simon Sedej, Mahmoud Abdellatif, Kristin Moreth, Guido Kroemer, Frauke Neff, Albrecht Schmidt, Emilie Schrepfer, Alexandros Rahn, Alexandra Harger, Guenter Haemmerle, Federico Pietrocola, Stephan J. Sigrist, Raimund Pechlaner, Kathrin Eller, Joern Dengjel, Christoph Magnes, Junichi Sadoshima, Corinna Simonini, Manuel Mayr, Zehan Hu, Marion von Frieling-Salewsky, Julia Schipke, Sabrina Büttner, Angelina S. Gross, Christoph Ruckenstuhl, Martin Hrabé de Angelis, Oskar Knittelfelder, and Frank Madeo
- Subjects
0301 basic medicine ,Male ,Aging ,Spermidine ,Physiology ,Gene Expression ,Blood Pressure ,Mass Spectrometry ,Mitochondria, Heart ,Autophagy-Related Protein 5 ,chemistry.chemical_compound ,Mice ,Diastole ,Surveys and Questionnaires ,Mitophagy ,Connectin ,Myocytes, Cardiac ,Prospective Studies ,Phosphorylation ,Heart metabolism ,Chromatography, High Pressure Liquid ,2. Zero hunger ,Cardioprotection ,Heart ,General Medicine ,Middle Aged ,RC667 ,3. Good health ,Cardiovascular Diseases ,Echocardiography ,Cytokines ,Female ,QP517 ,Adult ,medicine.medical_specialty ,Cardiotonic Agents ,ATG5 ,Immunoblotting ,Longevity ,Cardiomegaly ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Internal medicine ,medicine ,Autophagy ,Animals ,Humans ,QP506 ,Aged ,Heart Failure ,Inflammation ,Rats, Inbred Dahl ,Glucose Tolerance Test ,medicine.disease ,QP ,Diet ,Rats ,030104 developmental biology ,Endocrinology ,Blood pressure ,chemistry ,Heart failure ,Polyamine ,RC - 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.
- Published
- 2016