Cardioprotection and lifespan extension by the natural polyamine spermidine.
Tobias EisenbergMahmoud AbdellatifSabrina SchroederUwe PrimessnigSlaven StekovicTobias PendlAlexandra HargerJulia SchipkeAndreas ZimmermannAlbrecht SchmidtMingming TongChristoph RuckenstuhlChristopher DammbrueckAngelina S GrossViktoria HerbstChristoph MagnesGert TrausingerSophie NarathAndreas MeinitzerZehan HuAlexander KirschKathrin EllerDidac Carmona-GutierrezSabrina BüttnerFederico PietrocolaOskar KnittelfelderEmilie SchrepferPatrick RockenfellerCorinna SimoniniAlexandros RahnMarion HorschKristin MorethJohannes BeckersHelmut FuchsValerie Gailus-DurnerFrauke NeffDirk JanikBirgit RathkolbJan RozmanMartin Hrabě de AngelisTarek MoustafaGuenter HaemmerleManuel MayrPeter WilleitMarion von Frieling-SalewskyBurkert PieskeLuca ScorranoThomas PieberRaimund PechlanerJohann WilleitStephan J SigristWolfgang A LinkeChristian MühlfeldJunichi SadoshimaJoern DengjelStefan KiechlGuido KroemerSimon SedejFrank MadeoPublished in: Nature medicine (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.
Keyphrases
- blood pressure
- cardiovascular disease
- heart failure
- left ventricular
- oxidative stress
- hypertensive patients
- high fat diet induced
- cell death
- heart rate
- high glucose
- type diabetes
- signaling pathway
- endoplasmic reticulum stress
- diabetic rats
- cardiovascular events
- atrial fibrillation
- insulin resistance
- cardiac resynchronization therapy
- protein kinase
- cardiovascular risk factors
- risk assessment
- adipose tissue
- drug induced
- ejection fraction
- metabolic syndrome
- acute heart failure