Cardiac Aging - Benefits of Exercise, Nrf2 Activation and Antioxidant Signaling.
Cardiac Aging - Benefits of Exercise, Nrf2 Activation and Antioxidant Signaling.
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DOI：
10.1007/978-981-10-4307-9_13
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发表时间：
2017
影响因子：
--
通讯作者：
M. Narasimhan;N. Rajasekaran
中科院分区：
文献类型：
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作者：
M. Narasimhan;N. Rajasekaran
随着年龄的增长，心血管功能障碍和心力衰竭不仅会损害老年人的心功能，而且会影响老年人的生活质量，最终降低老年人的预期寿命。值得注意的是，心脏组织可以在某些条件下过早老化，例如基因突变、持续氧化还原应激和过载、异常分子信号传导、DNA损伤、端粒磨损和其他病理损伤。虽然心血管相关的发病率和死亡率正在上升，仍然是一个全球性的健康威胁，但在其医疗管理方面只有很少到适度的改善。这是由于生活方式的改变，年龄相关的心肌结构和功能重塑的分子机制是多因素的，并在不同的水平错综复杂地运作。沿着这些路线，内在的氧化还原机制和氧化应激（OS）在心肌中被广泛研究。随着年龄的增长，活性氧（ROS）的积累和由此产生的氧化损伤已被证明会增加心肌对多种并发症的易感性，如动脉粥样硬化、高血压、缺血性心脏病、心肌病和心力衰竭。人们越来越感兴趣的是试图增强中和ROS和减少OS的机制，作为一种可能的抗衰老干预措施和治疗年龄相关疾病。抗OS的天然防御系统涉及一种称为核红细胞2-p45相关因子2（nuclear erythroid-2-p45-related factor-2，Nrf 2）的主转录因子，该因子调节多个抗氧化基因。令人信服的证据存在于Nrf 2增益的功能，通过药理学干预措施，在抵消氧化损伤，并提供细胞保护，在几个器官，包括但不限于肺，肝，肾，脑等，然而，到目前为止，只有少数研究已经描述了Nrf 2的潜在作用，其非药理诱导心脏衰老。本章探讨了各种运动模式对Nrf 2信号传导的影响，沿着其对衰老心脏中OS级联反应的反应和后果。
Cardiovascular dysfunction and heart failure associated with aging not only impairs the cardiac function but also the quality of life eventually decreasing the life expectancy of the elderly. Notably, cardiac tissue can prematurely age under certain conditions such as genetic mutation, persistent redox stress and overload, aberrant molecular signaling, DNA damage, telomere attrition, and other pathological insults. While cardiovascular-related morbidity and mortality is on the rise and remains a global health threat, there has been only little to moderate improvements in its medical management. This is due to the fact that the lifestyle changes to molecular mechanisms underlying age-related myocardial structure and functional remodeling are multifactorial and intricately operate at different levels. Along these lines, the intrinsic redox mechanisms and oxidative stress (OS) are widely studied in the myocardium. The accumulation of reactive oxygen species (ROS) with age and the resultant oxidative damage has been shown to increase the susceptibility of the myocardium to multiple complications such as atherosclerosis, hypertension, ischemic heart disease, cardiac myopathy, and heart failure. There has been growing interest in trying to enhance the mechanisms that neutralize the ROS and curtailing OS as a possible anti-aging intervention and as a treatment for age-related disorders. Natural defense system to fight against OS involves a master transcription factor named nuclear erythroid-2-p45-related factor-2 (Nrf2) that regulates several antioxidant genes. Compelling evidence exists on the Nrf2 gain of function through pharmacological interventions in counteracting the oxidative damage and affords cytoprotection in several organs including but not limited to lung, liver, kidney, brain, etc. Nevertheless, thus far, only a few studies have described the potential role of Nrf2 and its non-pharmacological induction in cardiac aging. This chapter explores the effects of various modes of exercise on Nrf2 signaling along with its responses and ramifications on the cascade of OS in the aging heart.