Cardioprotection and Lifespan Extension by the Natural Polyamine Spermidine

Nat Med. 2016 Dec;22(12):1428-1438. doi: 10.1038/nm.4222. Epub 2016 Nov 14.

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.

MeSH terms

  • 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
  • Mitophagy / drug effects*
  • Myocytes, Cardiac / drug effects*
  • Phosphorylation / drug effects
  • Prospective Studies
  • Rats
  • Rats, Inbred Dahl
  • Spermidine / pharmacology*
  • Surveys and Questionnaires

Substances

  • Atg5 protein, mouse
  • Autophagy-Related Protein 5
  • Cardiotonic Agents
  • Connectin
  • Cytokines
  • Spermidine