Severity of cardiovascular disease increases markedly in elderly patients. In addition, many therapeutic strategies that decrease cardiac injury in adult patients are invalid in elderly patients. Thus, it is a challenge to protect the aged heart in the context of underlying chronic or acute cardiac diseases including ischemia-reperfusion injury. The cause(s) of this age-related increased damage remain unknown. Aging impairs the function of the mitochondrial electron transport chain (ETC), leading to decreased energy production and increased oxidative stress due to generation of reactive oxygen species (ROS). Additionally, ROS-induced oxidative stress can increase cardiac injury during ischemia-reperfusion by potentiating mitochondrial permeability transition pore (MPTP) opening. Aging leads to increased endoplasmic reticulum (ER) stress, which contributes to mitochondrial dysfunction, including reduced function of the ETC. The activation of both cytosolic and mitochondrial calcium-activated proteases termed calpains leads to mitochondrial dysfunction and decreased ETC function. Intriguingly, mitochondrial ROS generation also induces ER stress, highlighting the dynamic interaction between mitochondria and ER. Here, we discuss the role of ER stress in sensitizing and potentiating mitochondrial dysfunction in response to ischemia-reperfusion, and the promising potential therapeutic benefit of inhibition of ER stress and / or calpains to attenuate cardiac injury in elderly patients.

老年患者心血管疾病的严重程度显着增加。此外，许多减少成年患者心脏损伤的治疗策略对老年患者无效。因此，在包括缺血-再灌注损伤在内的潜在慢性或急性心脏疾病的情况下保护老年心脏是一项挑战。这种与年龄相关的损害增加的原因仍然未知。衰老会损害线粒体电子传递链 (ETC) 的功能，由于活性氧 (ROS) 的产生，导致能量产生减少和氧化应激增加。此外，ROS 诱导的氧化应激可通过增强线粒体通透性转换孔 (MPTP) 的开放来增加缺血再灌注期间的心脏损伤。衰老导致内质网 (ER) 应激增加，这会导致线粒体功能障碍，包括 ETC 功能降低。细胞溶质和线粒体钙激活蛋白酶（称为钙蛋白酶）的激活导致线粒体功能障碍和 ETC 功能降低。有趣的是，线粒体 ROS 的产生也诱导了内质网应激，突出了线粒体和内质网之间的动态相互作用。在这里，我们讨论了 ER 应激在响应缺血再灌注时敏感和增强线粒体功能障碍中的作用，以及抑制 ER 应激和/或钙蛋白酶以减轻老年患者心脏损伤的潜在治疗益处。细胞溶质和线粒体钙激活蛋白酶（称为钙蛋白酶）的激活导致线粒体功能障碍和 ETC 功能降低。有趣的是，线粒体 ROS 的产生也诱导了内质网应激，突出了线粒体和内质网之间的动态相互作用。在这里，我们讨论了内质网应激在响应缺血再灌注时敏感和增强线粒体功能障碍的作用，以及抑制内质网应激和/或钙蛋白酶以减轻老年患者心脏损伤的潜在治疗益处。细胞溶质和线粒体钙激活蛋白酶（称为钙蛋白酶）的激活导致线粒体功能障碍和 ETC 功能降低。有趣的是，线粒体 ROS 的产生也诱导了内质网应激，突出了线粒体和内质网之间的动态相互作用。在这里，我们讨论了内质网应激在响应缺血再灌注时敏感和增强线粒体功能障碍的作用，以及抑制内质网应激和/或钙蛋白酶以减轻老年患者心脏损伤的潜在治疗益处。