Protein acetylation in cardiac aging.
Protein acetylation in cardiac aging.
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DOI：
10.1016/j.yjmcc.2021.04.007
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发表时间：
2021-08
影响因子：
5
通讯作者：
Stratton, Matthew S.
中科院分区：
文献类型：
--
作者：
Francois, Ashley;Canella, Alessandro;Marcho, Lynn M.;Stratton, Matthew S.
生物衰老归因于控制遗传和代谢完整性的系统进行性功能障碍。在细胞水平上，衰老通过累积的 DNA 损伤和突变、活性氧、脂质和蛋白质的交替修饰、基因表达程序的交替以及线粒体功能障碍而表现出来。这些影响总和导致组织形态改变和器官功能障碍。蛋白质酰化已成为这些过程中年龄依赖性变化的关键介质。尽管学术界和工业界几十年来一直在关注心力衰竭的研究，但心力衰竭仍然是美国主要的死亡原因，心力衰竭的 5 年死亡率仍然超过 40%。超过 90% 的心力衰竭死亡发生在 65 岁以上的患者中，心力衰竭是 Medicare 受益人住院的主要原因。 1931 年，科尔和科赫发现骨骼肌中磷酸盐的积累与年龄有关。这些和类似的发现为现已被广泛接受的新陈代谢与衰老之间的联系理论提供了支持证据。近二十年后，人们描述了心脏中与年龄相关的生化分子变化。从这些小小的开始，该领域近年来取得了长足的发展。对心脏衰老的研究日益关注，部分原因是多个公共卫生领域的进步推动了衰老相关疾病在人群水平上的临床表现。据估计，到 2030 年，全球人口的 25% 将超过 65 岁。这篇综述概述了与心脏衰老相关的生物过程的乙酰化依赖性调节，并介绍了心脏功能和衰老中新兴的非乙酰、酰基赖氨酸修饰。
Biological aging is attributed to progressive dysfunction in systems governing genetic and metabolic integrity. At the cellular level, aging is evident by accumulated DNA damage and mutation, reactive oxygen species, alternate lipid and protein modifications, alternate gene expression programs, and mitochondrial dysfunction. These effects sum to drive altered tissue morphology and organ dysfunction. Protein-acylation has emerged as a critical mediator of age-dependent changes in these processes. Despite decades of research focus from academia and industry, heart failure remains a leading cause of death in the United States while the 5 year mortality rate for heart failure remains over 40%. Over 90% of heart failure deaths occur in patients over the age of 65 and heart failure is the leading cause of hospitalization in Medicare beneficiaries. In 1931, Cole and Koch discovered age-dependent accumulation of phosphates in skeletal muscle. These and similar findings provided supporting evidence for, now well accepted, theories linking metabolism and aging. Nearly two decades later, age-associated alterations in biochemical molecules were described in the heart. From these small beginnings, the field has grown substantially in recent years. This growing research focus on cardiac aging has, in part, been driven by advances on multiple public health fronts that allow population level clinical presentation of aging related disorders. It is estimated that by 2030, 25% of the worldwide population will be over the age of 65. This review provides an overview of acetylation-dependent regulation of biological processes related to cardiac aging and introduces emerging non-acetyl, acyl-lysine modifications in cardiac function and aging.
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选择性抑制BET溴结构域。
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