Cardioprotection and lifespan extension by the natural polyamine spermidine

被引：988

作者：

Eisenberg, Tobias ^{[1
,2
]}

Abdellatif, Mahmoud ^{[3
]}

Schroeder, Sabrina ^{[1
]}

Primessnig, Uwe ^{[3
,4
]}

Stekovic, Slaven ^{[1
]}

Pendl, Tobias ^{[1
]}

Harger, Alexandra ^{[1
,5
]}

Schipke, Julia ^{[6
,7
]}

Zimmermann, Andreas ^{[1
]}

Schmidt, Albrecht ^{[3
]}

Tong, Mingming ^{[8
]}

Ruckenstuhl, Christoph ^{[1
]}

Dammbrueck, Christopher ^{[1
]}

Gross, Angelina S. ^{[1
]}

Herbst, Viktoria ^{[3
]}

Magnes, Christoph ^{[9
]}

Trausinger, Gert ^{[9
]}

Narath, Sophie ^{[9
]}

Meinitzer, Andreas ^{[10
]}

Hu, Zehan ^{[11
,12
]}

Kirsch, Alexander ^{[13
]}

Eller, Kathrin ^{[13
]}

Carmona-Gutierrez, Didac ^{[1
]}

Buettner, Sabrina ^{[1
,14
]}

Pietrocola, Federico ^{[15
,16
,18
,19
]}

Knittelfelder, Oskar ^{[1
]}

Schrepfer, Emilie ^{[20
,21
]}

Rockenfeller, Patrick ^{[1
,22
]}

Simonini, Corinna ^{[3
]}

Rahn, Alexandros ^{[6
]}

Horsch, Marion ^{[23
]}

Moreth, Kristin ^{[23
]}

Beckers, Johannes ^{[23
,24
,25
]}

Fuchs, Helmut ^{[23
]}

Gailus-Durner, Valerie ^{[23
]}

Neff, Frauke ^{[23
,26
]}

Janik, Dirk ^{[23
,26
]}

Rathkolb, Birgit ^{[23
,25
,27
]}

Rozman, Jan ^{[23
,25
]}

de Angelis, Martin Hrabe ^{[23
,24
,25
]}

Moustafa, Tarek ^{[1
,5
]}

Haemmerle, Guenter ^{[1
]}

Mayr, Manuel ^{[28
]}

Willeit, Peter ^{[29
,30
]}

von Frieling-Salewsky, Marion ^{[31
]}

Pieske, Burkert ^{[3
,4
,32
]}

Scorrano, Luca ^{[20
,21
]}

Pieber, Thomas ^{[5
,9
]}

Pechlaner, Raimund ^{[29
]}

Willeit, Johann ^{[29
]}

机构：

[1] Graz Univ, Inst Mol Biosci, NAWI Graz, Graz, Austria

[2] BioTechMed Graz, Graz, Austria

[3] Med Univ Graz, Dept Cardiol, Graz, Austria

[4] Charite, Dept Internal Med & Cardiol, Campus Virchow Klinikum, Berlin, Germany

[5] Med Univ Graz, Dept Internal Med, Graz, Austria

[6] Hannover Med Sch, Inst Funct & Appl Anat, Hannover, Germany

[7] Cluster Excellence REBIRTH Regenerat Biol Reconst, Hannover, Germany

[8] Rutgers New Jersey Med Sch, Dept Cell Biol & Mol Med, Newark, NJ USA

[9] Joanneum Res Forsch Gesell mbH, HLTH, Inst Biomed & Hlth Sci, Graz, Austria

[10] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria

[11] Univ Freiburg, FRIAS Freiburg Inst Adv Studies, ZBSA Ctr Biol Syst Anal, Dept Dermatol,Med Ctr,BIOSS Ctr Biol Signalling S, Freiburg, Germany

[12] Univ Fribourg, Dept Biol, Fribourg, Switzerland

[13] Med Univ Graz, Clin Div Nephrol, Graz, Austria

[14] Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden

[15] Ctr Rech Cordeliers, Equipe Labellisee Ligue Canc 11, Paris, France

[16] Gustave Roussy Comprehens Canc Ctr, Cell Biol & Metabol Platforms, Villejuif, France

[17] INSERM, U1138, Paris, France

[18] Univ Paris 05, Sorbonne Paris Cite, Paris, France

[19] Univ Paris 06, Paris, France

[20] Univ Padua, Dept Biol, Padua, Italy

[21] Venetian Inst Mol Med, Dulbecco Telethon Inst, Padua, Italy

[22] Univ Kent, Sch Biosci, Kent Fungal Grp, Canterbury, Kent, England

[23] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, German Mouse Clin, Inst Expt Genet, Neuherberg, Germany

[24] Tech Univ Munich, Chair Expt Genet, Sch Life Sci Weihenstephan, Freising Weihenstephan, Germany

[25] German Ctr Diabet Res DZD, Neuherberg, Germany

[26] Helmholtz Zentrum Munchen, Inst Pathol, German Res Ctr Environm Hlth, Neuherberg, Germany

[27] Ludwig Maximilians Univ Munchen, Inst Mol Anim Breeding & Biotechnol, Gene Ctr, Munich, Germany

[28] Kings Coll London, Kings British Heart Fdn Ctr, London, England

[29] Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria

[30] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[31] Ruhr Univ Bochum, Dept Cardiovasc Physiol, Bochum, Germany

[32] German Heart Ctr Berlin, Dept Internal Med & Cardiol, Berlin, Germany

[33] Free Univ Berlin, Inst Biol, Berlin, Germany

[34] Charite, NeuroCure, Berlin, Germany

[35] Hop Europeen Georges Pompidou, Pole Biol, Paris, France

[36] Karolinska Inst, Dept Womens & Childrens Hlth, Karolinska Univ Hosp, Stockholm, Sweden

来源：

NATURE MEDICINE | 2016年 / 22卷 / 12期

基金：

奥地利科学基金会; 瑞典研究理事会; 欧洲研究理事会; 瑞士国家科学基金会;

关键词：

CONGESTIVE-HEART-FAILURE; EJECTION FRACTION; ARGININE BIOAVAILABILITY; MITOCHONDRIAL AUTOPHAGY; MYOCARDIAL HYPERTROPHY; ROBUST QUANTIFICATION; AMINO-ACIDS; MICE; MASS; DYSFUNCTION;

D O I：

10.1038/nm.4222

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1428 / +

页数：17

共 88 条

[1]

Spectral transfer function analysis of respiratory hemodynamic fluctuations predicts end-diastolic stiffness in preserved ejection fraction heart failure [J].