Cardioprotection and lifespan extension by the natural polyamine spermidine

By T. Eisenberg, M. Abdellatif, Sabrina Schroeder, U. Primessnig, Slaven Stekovic, T. Pendl, A. Harger, J. Schipke, Andreas Zimmermann, A. Schmidt and 49 more. Nature Medicine, 2016

1,039 citations recorded by the source corpus.

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.

Subfields: Epidemiology, Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/70d811ce1dbf1feb9b330d5e8a4ca77d61db91c7

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Citations in the corpus

Spermidine in health and disease (2018, background): “The spermidine-mediated ultrastructural and functional improvement of mitochondria from aged cardiac muscles (44) and from skeletal muscle (stem) cells (70–72) further support the potential utility of spermidine in the treatment of muscle-related disorders.”
Health Benefits of the Mediterranean Diet: Metabolic and Molecular Mechanisms (2018, neutral): “Spermidine is known to inhibit histone acetyltransferases, which results in higher resistance to oxidative stress, to increase autophagy as well as to markedly reduce subclinical inflammation and the rates of cell necrosis during aging (60).”
Autophagy and Mitophagy in Cardiovascular Disease. (2017, background): “A 40% decrease in caloric intake limited cardiac senescence and improved diastolic function in 8-month-old Fischer rats, a beneficial effect that was associated with autophagy activation in the myocardium.41 Caloric restriction and the administration of rapamycin reversed age-dependent cardiac hyper”