Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Geriatr Gerontol Int. 2011 Apr;11(2):143-56. doi: 10.1111/j.1447-0594.2010.00675.x. Epub 2011 Jan 4.
Caloric restriction is an established intervention, of which anti-aging effects are scientifically proven. It has pleiotropic effects on the cardiovascular system: vascular protection, improvement of myocardial ischemic tolerance and retardation of cardiac senescence. First, increasing evidence from both experimental and clinical studies supports the concept that "a man is as old as his arteries". Caloric restriction could prevent the progression of atherosclerosis and vascular aging through direct and indirect mechanisms. Second, the hearts of senescent animals are more susceptible to ischemia than those of young animals. We demonstrated that short-term and prolonged caloric restriction confers cardioprotection against ischemia/reperfusion injury in young and aged rodents. Furthermore, we showed that the increase in circulating adiponectin levels and subsequent activation of adenosine monophosphate-activated protein kinase are necessary for the cardioprotection afforded by short-term caloric restriction. In contrast, the mechanisms by which prolonged caloric restriction confers cardioprotection seem more complicated. Adiponectin, nitric oxide synthase and sirtuin may form a network of cardiovascular protection during caloric restriction. Recently, by using genetically engineered mice, we found that, in addition to endothelial nitric oxide synthase, neuronal nitric oxide synthase plays an essential role in the development of cardioprotection afforded by prolonged caloric restriction. Third, long-term caloric restriction has cardiac-specific effects that attenuate the age-associated impairment seen in left ventricular diastolic function. It is possible that long-term caloric restriction partially retards cardiac senescence by attenuating oxidative damage in the aged heart. Overall, we strongly believe that caloric restriction could reduce morbidity and mortality of cardiovascular events in humans.
热量限制是一种已被证实的干预措施，其抗衰老作用已得到科学验证。它对心血管系统有多种作用：血管保护、改善心肌缺血耐受和延缓心脏衰老。首先，越来越多的实验和临床研究证据支持“人的动脉有多老，人就有多老”这一概念。热量限制可以通过直接和间接机制预防动脉粥样硬化和血管老化的进展。其次，衰老动物的心脏比年轻动物更容易发生缺血。我们证明，短期和长期热量限制可使年轻和老年啮齿动物的心脏对缺血/再灌注损伤产生保护作用。此外，我们还表明，循环脂联素水平的升高和随后的腺苷一磷酸激活蛋白激酶的激活，是短期热量限制提供的心脏保护所必需的。相比之下，长期热量限制提供心脏保护的机制似乎更为复杂。脂联素、一氧化氮合酶和沉默调节蛋白可能在热量限制期间形成心血管保护网络。最近，通过使用基因工程小鼠，我们发现，除了内皮型一氧化氮合酶外，神经元型一氧化氮合酶在长期热量限制提供的心脏保护的发展中也起着至关重要的作用。第三，长期热量限制对心脏有特异性作用，可以减轻左心室舒张功能随年龄增长而出现的损害。长期热量限制可能通过减轻衰老心脏的氧化损伤，部分延缓心脏衰老。总的来说，我们坚信热量限制可以降低人类心血管事件的发病率和死亡率。
