Cardioprotection and lifespan extension by the natural polyamine spermidine.
Nat. Med. 22, 1428-1438 (2016)
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Preserved Ejection Fraction; Diastolic Heart-failure; Tandem Mass-spectrometry; Salt-sensitive Rats; Pressure-overload; Amino-acids; Arginine Bioavailability; Mitochondrial Autophagy; Myocardial Hypertrophy; Robust Quantification
ISSN (print) / ISBN 1078-8956
Zeitschrift Nature medicine
Quellenangaben Band: 22, Heft: 12, Seiten: 1428-1438
Verlag Nature Publ. Co.
Verlagsort New York, NY