RRC ID 47771
Author 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 AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Carmona-Gutierrez D, Büttner 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 MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Mühlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F.
Title Cardioprotection and lifespan extension by the natural polyamine spermidine.
Journal Nat. Med.
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.
Volume 22(12)
Pages 1428-1438
Published 2016-12
DOI 10.1038/nm.4222
PII nm.4222
PMID 27841876
PMC PMC5806691
MeSH Adult Aged Aging / drug effects* Aging / immunology Aging / metabolism Animals Autophagy / drug effects* Autophagy-Related Protein 5 / genetics Blood Pressure / drug effects* Cardiomegaly / diagnostic imaging Cardiotonic Agents / pharmacology Cardiovascular Diseases / epidemiology Chromatography, High Pressure Liquid Connectin / drug effects Connectin / metabolism Cytokines / drug effects Cytokines / immunology Diastole Diet / statistics & numerical data Echocardiography Female Gene Expression / drug effects Glucose Tolerance Test Heart / diagnostic imaging Heart / drug effects* Heart Failure Humans Immunoblotting Inflammation Longevity / drug effects* Male Mass Spectrometry Mice Middle Aged Mitochondria, Heart / drug effects* Mitochondria, Heart / metabolism Mitochondrial Degradation / drug effects* Myocytes, Cardiac / drug effects* Phosphorylation / drug effects Prospective Studies Rats Rats, Inbred Dahl Spermidine / pharmacology* Surveys and Questionnaires
IF 32.621
Times Cited 8
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
Resource
Mice B6.129S-Atg5<tm1Myok>(RBRC02975)