Dong Ming, Yang Ziyi, Fang Hongcheng, Xiang Jiaqing, Xu Cong, Zhou Yanqing, Wu Qianying, Liu Jie
1Department of Pathophysiology, Guangdong Key Laboratory of Genome Stability and Human Disease Prevention, Shenzhen University Health Science Center, Guangdong, China.
2Shenzhen Shajing Hospital, Affiliated of Guangzhou Medical University, Shenzhen, Guangdong, China.
Aging Dis. 2020 Mar 9;11(2):365-376. doi: 10.14336/AD.2019.0522. eCollection 2020 Apr.
Cardiac function of the human heart changes with age. The age-related change of systolic function is subtle under normal conditions, but abrupt under stress or in a pathogenesis state. Aging decreases the cardiac tolerance to stress and increases susceptibility to ischemia, which caused by aging-induced Ca transient impairment and metabolic dysfunction. The changes of contractility proteins and the relative molecules are in a non-linear fashion. Specifically, the expression and activation of cMLCK increase first then fall during ischemia and reperfusion (I/R). This change is responsible for the nonmonotonic contractility alteration in I/R which the underlying mechanism is still unclear. Contractility recovery in I/R is also attenuated by age. The age-related change in cardiac contractility influences the therapeutic effect and intervention timepoint. For most cardiac ischemia therapies, the therapeutic result in the elderly is not identical to the young. Anti-aging treatment has the potential to prevent the development of ischemic injury and improves cardiac function. In this review we discuss the mechanism underlying the contractility changes in the aged heart and age-induced ischemic injury. The potential mechanism underlying the increased susceptibility to ischemic injury in advanced age is highlighted. Furthermore, we discuss the effect of age and the administration time for intervention in cardiac ischemia therapies.
人类心脏的心脏功能随年龄而变化。在正常情况下，收缩功能与年龄相关的变化较为细微，但在应激状态或发病状态下则较为明显。衰老会降低心脏对压力的耐受性，并增加对缺血的易感性，这是由衰老引起的钙瞬变损伤和代谢功能障碍所致。收缩蛋白及相关分子的变化呈非线性方式。具体而言，在缺血再灌注（I/R）过程中，钙调蛋白依赖的肌球蛋白轻链激酶（cMLCK）的表达和激活先升高后降低。这种变化导致了I/R过程中收缩力的非单调改变，其潜在机制仍不清楚。I/R过程中的收缩力恢复也会因年龄而减弱。心脏收缩力与年龄相关的变化会影响治疗效果和干预时间点。对于大多数心脏缺血治疗而言，老年人的治疗结果与年轻人并不相同。抗衰老治疗有可能预防缺血性损伤的发展并改善心脏功能。在本综述中，我们讨论了老年心脏收缩力变化及年龄诱导的缺血性损伤的潜在机制。重点强调了高龄时对缺血性损伤易感性增加的潜在机制。此外，我们还讨论了年龄及干预给药时间对心脏缺血治疗的影响。
