"Inside every old person is a young person wondering what happened." So, what is aging? Aging is a manifestation of progressive, time-dependent failure of molecular mechanisms that create disorder within a system of DNA and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere, universe). Continuous signaling, transmitted with different kinetics across each of these environments, confers a "mutual enslavement" that creates ordered functions among the components within the system. Accrual of this molecular disorder over time, i.e. during aging, causes progressive changes in the structure and function of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of signaling within the DNA environment system within the heart and arteries become disordered with advancing age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation and nitration phosphorylation, lead to altered misfolding and disordered molecular interactions. The stoichiometry and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is not executed by "professional" inflammatory cells (i.e. white blood cells), however, but by activation of renin-angiotensin-aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and cardiac cells' phenotype shifts, resulting in production of inflammatory cytokines. Progressive molecular disorder within the heart and arteries over time leads to an excessive allostatic load on the CV system, that results in an increase and "overshoot" in the inflammatory defense signaling. This age-associated molecular disorder-induced inflammation that accrues in the heart and arteries does not, itself, cause clinical signs or symptoms of CVD. Clinical signs and symptoms of these CVDs begin to emerge, however, when the age-associated inflammation in the heart and arteries exceeds a threshold. Thus, an emerging school of thought is that accelerated age-associated alterations within the heart and arteries, per se, ought to be considered to be a type of CVD, because the molecular disorder and the inflammatory milieu it creates within the heart and arteries with advancing age are the roots of the pathophysiology of most cardiovascular diseases, e.g. athersclerosis and hypertension. Because many effects of aging on the CV system can be delayed or attenuated by changes in lifestyle, e.g. diet and exercise, or by presently available drugs, e.g. those that suppress Ang II signaling, CV aging is a promising frontier in preventive cardiology that is not only ripe for, but also in dire need of attention! There is an urgency to incorporate the concept of cardiovascular aging as a disease into clinical medicine. But, sadly, the reality of the age-associated molecular disorder within the heart and ateries has, for the most part, been kept outside of mainstream clinical medicine. This article is part of a Special Issue entitled CV Aging.

中文翻译：

---

所以！什么是老化？心血管衰老是一种疾病吗？

“每个老人的内心都有一个年轻人，想知道发生了什么。” 那么，什么是衰老呢？衰老是分子机制渐进性、时间依赖性失效的表现，这些失效在 DNA 系统及其环境（核、细胞质、组织、器官、生物体、其他生物体、社会、陆地、大气、宇宙）内造成紊乱。连续信号以不同的动力学在每个环境中传输，赋予“相互奴役”，从而在系统内的组件之间创建有序的功能。随着时间的推移，即在衰老过程中，这种分子紊乱的累积会导致心脏和动脉的结构和功能发生渐进性变化，这在人类、非人类灵长类动物、兔子和大鼠中非常相似，从而损害心血管储备功能，并赋予显着的心血管储备功能。发生心血管疾病的风险。随着年龄的增长，心脏和动脉内 DNA 环境系统内信号传导的几乎所有方面都会变得紊乱：信号发生变化，信号感知、信号传输和信号响应、细胞更新受损、由于改变而导致的蛋白质组变化基因组转录、mRNA 翻译和蛋白质稳态。一些分子的密度降低，翻译后修饰（例如氧化和硝化磷酸化）导致错误折叠改变和分子相互作用紊乱。酶的化学计量和动力学以及构成关键心脏和血管细胞功能以及去除受损细胞器和蛋白质的强大储备机制基础的那些反应恶化。CV 细胞产生炎症防御，试图限制分子紊乱。然而，由此产生的促炎环境并不是由“专业”炎症细胞（即白细胞）执行的，而是通过激活肾素-血管紧张素-醛固酮内皮素信号级联来执行的，该级联会导致内皮和血管平滑肌以及心肌细胞的表型转变，从而导致炎症细胞因子的产生。随着时间的推移，心脏和动脉内的进行性分子紊乱会导致心血管系统的过度稳态负荷，从而导致炎症防御信号的增加和“超调”。这种在心脏和动脉中产生的与年龄相关的分子紊乱引起的炎症本身不会引起 CVD 的临床体征或症状。然而，当心脏和动脉中与年龄相关的炎症超过阈值时，这些心血管疾病的临床体征和症状就开始出现。因此，一个新兴的思想流派认为，心脏和动脉内与年龄相关的加速变化本身应该被认为是心血管疾病的一种，因为它在心脏和动脉内产生的分子紊乱和炎症环境年龄增长是大多数心血管疾病病理生理学的根源，例如动脉粥样硬化和高血压。由于生活方式的改变（例如饮食和锻炼）或目前可用的药物（例如抑制血管紧张素II信号传导的药物）可以延迟或减弱衰老对心血管系统的许多影响，因此心血管衰老是预防心脏病学中一个有前途的前沿领域。水到渠成，还急需重视！迫切需要将心血管衰老作为一种疾病的概念纳入临床医学。但遗憾的是，心脏和动脉内与年龄相关的分子疾病的现实在很大程度上被排除在主流临床医学之外。本文是题为 CV Aging 的特刊的一部分。