Department of Pathology, University of Washington, Seattle, Washington, USA.
Antioxid Redox Signal. 2012 Jun 15;16(12):1492-526. doi: 10.1089/ars.2011.4179. Epub 2012 Apr 3.
Cardiovascular diseases (CVDs) are the major causes of death in the western world. The incidence of cardiovascular disease as well as the rate of cardiovascular mortality and morbidity increase exponentially in the elderly population, suggesting that age per se is a major risk factor of CVDs. The physiologic changes of human cardiac aging mainly include left ventricular hypertrophy, diastolic dysfunction, valvular degeneration, increased cardiac fibrosis, increased prevalence of atrial fibrillation, and decreased maximal exercise capacity. Many of these changes are closely recapitulated in animal models commonly used in an aging study, including rodents, flies, and monkeys. The application of genetically modified aged mice has provided direct evidence of several critical molecular mechanisms involved in cardiac aging, such as mitochondrial oxidative stress, insulin/insulin-like growth factor/PI3K pathway, adrenergic and renin angiotensin II signaling, and nutrient signaling pathways. This article also reviews the central role of mitochondrial oxidative stress in CVDs and the plausible mechanisms underlying the progression toward heart failure in the susceptible aging hearts. Finally, the understanding of the molecular mechanisms of cardiac aging may support the potential clinical application of several "anti-aging" strategies that treat CVDs and improve healthy cardiac aging.
心血管疾病 (CVDs) 是西方世界主要的死亡原因。心血管疾病的发病率以及心血管死亡率和发病率在老年人群中呈指数级增长，这表明年龄本身就是 CVDs 的一个主要危险因素。人类心脏衰老的生理变化主要包括左心室肥厚、舒张功能障碍、瓣膜退化、心肌纤维化增加、心房颤动的患病率增加以及最大运动能力下降。这些变化中的许多在常用于衰老研究的动物模型中得到了很好的重现，包括啮齿动物、苍蝇和猴子。转基因老年小鼠的应用为心脏衰老涉及的几个关键分子机制提供了直接证据，例如线粒体氧化应激、胰岛素/胰岛素样生长因子/PI3K 通路、肾上腺素能和肾素血管紧张素 II 信号以及营养信号通路。本文还综述了线粒体氧化应激在 CVDs 中的核心作用以及易感衰老心脏中心力衰竭进展的潜在机制。最后，对心脏衰老分子机制的理解可能支持几种“抗衰老”策略的潜在临床应用，这些策略可治疗 CVDs 并改善健康的心脏衰老。
