Department of Clinical Pharmacy and Pharmacology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Department of Physiology, Amsterdam Cardiovascular Sciences, VU University Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
Nat Rev Cardiol. 2017 Nov;14(11):637-653. doi: 10.1038/nrcardio.2017.89. Epub 2017 Jun 29.
The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing. Failure of protein quality control involves impairment of chaperones, ubiquitin-proteosomal systems, autophagy, and loss of sarcomeric and cytoskeletal proteins, all of which relate to induction of cardiomyocyte senescence. Targeting protein quality control to maintain cardiac proteostasis offers a novel therapeutic strategy to promote cardiac health and combat cardiac disease. Currently marketed drugs are available to explore this concept in the clinical setting.
由于人口老龄化，心脏病的发病率和患病率（全球主要死因）可能会增加。关于衰老机制的主流理论以细胞蛋白质稳态（蛋白质稳态）的逐渐脱轨和蛋白质质量控制的丧失为核心因素。在心脏中，由于遗传设计缺陷或环境诱导的“磨损”，蛋白质通透性丧失会使蛋白质质量控制不堪重负，从而导致蛋白质稳态脱轨，并导致心脏衰老。蛋白质质量控制的失败涉及伴侣蛋白、泛素-蛋白酶体系统、自噬以及肌节和细胞骨架蛋白的丧失，所有这些都与诱导心肌细胞衰老有关。靶向蛋白质质量控制以维持心脏蛋白质稳态为促进心脏健康和对抗心脏疾病提供了一种新的治疗策略。目前市场上有药物可用于在临床环境中探索这一概念。
