Cardioprotection and lifespan extension by the natural polyamine spermidine

• DOI: 10.1038/nm.4222
• Publication Date: 2016-11-14T16:55:09Z
• Authors: Tobias Eisenberg; Mahmoud Abdellatif; Sabrina Schroeder; Uwe Primessnig; Slaven Stekovic; Tobias Pendl; Alexandra Harger; Julia Schipke; Andreas Zimmermann; Albrecht Schmidt; Mingming Tong; Christoph Ruckens...; Christopher Dammb...; Angelina S Gross; Viktoria Herbst; Christoph Magnes; Gert Trausinger; Sophie Narath; Andreas Meinitzer; Zehan Hu; Alexander Kirsch; Kathrin Eller; Didac Carmona-Gut...; Sabrina Büttner; Federico Pietrocola; Oskar Knittelfelder; Emilie Schrepfer; Patrick Rockenfeller; Corinna Simonini; Alexandros Rahn; Marion Horsch; Kristin Moreth; Johannes Beckers; Helmut Fuchs; Valerie Gailus-Du...; Frauke Neff; Dirk Janik; Birgit Rathkolb; Jan Rozman; Martin Hrabe de A...; Tarek Moustafa; Guenter Haemmerle; Manuel Mayr; Peter Willeit; Marion von Frieli...; Burkert Pieske; Luca Scorrano; Thomas Pieber; Raimund Pechlaner; Johann Willeit; Stephan J Sigrist; Wolfgang A Linke; Christian Mühlfeld; Junichi Sadoshima; Joern Dengjel; Stefan Kiechl; Guido Kroemer; Simon Sedej; Frank Madeo
• Keywords: Adult; 0301 basic medicine; Aging; Cardiotonic Agents; 610; Gene Expression; Blood Pressure; Cardiomegaly; Autophagy-Related Protein 5; 03 medical and health sciences; Diastole; Autophagy; Animals; Connectin; QP506; Chromatography, High Pressure Liquid; Aged; 2. Zero hunger; Q; R; Heart; Glucose Tolerance Test; QP; RC667; Diet; 3. Good health; [SDV] Life Sciences [q-bio]; Cardiovascular Diseases; Echocardiography; Cytokines; Female; QP517; RC

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.