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Cardioprotection and lifespan extension by the natural polyamine spermidine
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Journal Article
Cardioprotection and lifespan extension by the natural polyamine spermidine
2016
Overview
Spermidine, a naturally occurring polyamine, extends the lifespan of mice and is cardioprotective in both aged mice and hypertensive rats. In humans, high dietary spermidine intake is associated with reduced blood pressure and a lower incidence of cardiovascular disease.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Aging
/ Animals
/ Autophagy-Related Protein 5 - genetics
/ Blood Pressure - drug effects
/ Cardiomegaly - diagnostic imaging
/ Cardiotonic Agents - pharmacology
/ Cardiovascular Diseases - epidemiology
/ Chromatography, High Pressure Liquid
/ Diastole
/ Diet - statistics & numerical data
/ Feeding
/ Female
/ Gene Expression - drug effects
/ Humans
/ Male
/ Mice
/ Mitochondria, Heart - drug effects
/ Mitochondria, Heart - metabolism
/ Myocytes, Cardiac - drug effects
/ Phosphorylation - drug effects
/ Rats
/ Salts
