天然多胺亚精胺的心脏保护和延长寿命

Cardioprotection and lifespan extension by the natural polyamine spermidine

Keywords：Myocardium, mitochondria, spermidine, oxidative phosphorylation capacity

关键词：心肌、线粒体、亚精胺、氧化磷酸化能力

组织：心脏
作者：Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Ruckenstuhl C, Dammbrueck C, Gross AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, CarmonaGutierrez D, Büttner S, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Horsch M, Moreth K, Beckers J, Fuchs H, Gailus-Durner V, Neff F, Janik D, Rathkolb B, Rozman J, de Angelis MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Mühlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F.
出版期刊：《Nature Medicine》2021/2/3

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 hypertensioninduced 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 the protection from cardiovascular disease.

文章摘要：

衰老与心血管疾病和死亡的风险增加有关。在这里，我们展示了口服补充天然多胺亚精胺可延长小鼠的寿命并发挥心脏保护作用，减少老年小鼠的心脏肥大并保持舒张功能。亚精胺喂养增强了心脏自噬、线粒体自噬和线粒体呼吸，还改善了体内心肌细胞的机械弹性特性，同时增加了肌联蛋白磷酸化并抑制了亚临床炎症。亚精胺喂养未能在心肌细胞中缺乏自噬相关蛋白 Atg5 的小鼠中提供心脏保护。在喂食高盐饮食（高血压诱发充血性心力衰竭模型）的达尔盐敏感大鼠中，亚精胺喂养可降低全身血压，增加肌联蛋白磷酸化并防止心脏肥大和舒张功能下降，从而延缓心脏进展失败。根据食物问卷评估，在人类中，高水平的膳食亚精胺与血压降低和心血管疾病发病率降低相关。我们的研究结果表明了一种新的可行的预防心血管疾病的策略。Spermidine是一种天然类药物，实验表明Spermidine可改善小鼠的心肌细胞组成以及线粒体功能。在C57BL/6雄性小鼠的生命后期添加喂食药物 Spermidine（+S），并对24月龄小鼠的心肌纯化线粒体进行能量代谢分析。实验过程中可见，当滴加试剂ADP用于启动ATP合酶功能，将TCA产生的电子传递与磷酸化过程进行耦联，服用Spermidine（+S）的小鼠心肌纯化线粒体的功能较对照组小鼠有明显的上升，数据统计可见Spermidine（+S）药物可改善线粒体中的ATP合酶的功能，进而提高线粒体的氧化磷酸化能力。

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