The circadian clock and extracellular matrix homeostasis in aging and age-related diseases.
The circadian clock and extracellular matrix homeostasis in aging and age-related diseases.
复制标题
衰老和年龄相关疾病中的生物钟和细胞外基质稳态。
DOI：
10.1152/ajpcell.00122.2023
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Dudek M
中科院分区：
文献类型：
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作者：
Dudek M
细胞外基质（ECM）是存在于所有组织和器官内的非细胞支架成分。它提供了重要的生物化学和生物力学线索来指导细胞行为，并已被证明是在昼夜节律钟调节下，这是一种高度保守的细胞内在计时机制，随着24小时的节奏环境而进化。衰老是许多疾病的主要风险因素，包括癌症、纤维化和神经退行性疾病。衰老和我们的现代24/7社会都会扰乱昼夜节律，这可能会导致ECM稳态的改变。了解ECM的日常动态以及这种机制如何随年龄变化将对组织健康，疾病预防和改善治疗产生深远的影响。保持有节奏的振荡被认为是健康的标志。另一方面，衰老的许多标志是昼夜节律计时机制的关键调节器。在这篇综述中，我们总结了ECM与生物钟和组织衰老的新工作。我们讨论了在衰老过程中ECM的生物力学和生化特性的变化可能有助于生物钟失调。我们还考虑了如何阻尼时钟随着年龄的增长可能会损害日常动态调节ECM稳态在基质丰富的组织。这篇综述的目的是鼓励新的概念和可检验的假说之间的双向相互作用的生物钟和ECM的背景下老化。
The extracellular matrix (ECM) is the noncellular scaffolding component present within all tissues and organs. It provides crucial biochemical and biomechanical cues to instruct cellular behavior and has been shown to be under circadian clock regulation, a highly conserved cell-intrinsic timekeeping mechanism that has evolved with the 24-hour rhythmic environment. Aging is a major risk factor for many diseases, including cancer, fibrosis, and neurodegenerative disorders. Both aging and our modern 24/7 society disrupt circadian rhythms, which could contribute to altered ECM homeostasis. Understanding the daily dynamics of ECM and how this mechanism changes with age will have a profound impact on tissue health, disease prevention, and improving treatments. Maintaining rhythmic oscillations has been proposed as a hallmark of health. On the other hand, many hallmarks of aging turn out to be key regulators of circadian timekeeping mechanisms. In this review, we summarize new work linking the ECM with circadian clocks and tissue aging. We discuss how the changes in the biomechanical and biochemical properties of ECM during aging may contribute to circadian clock dysregulation. We also consider how the dampening of clocks with age could compromise the daily dynamic regulation of ECM homeostasis in matrix-rich tissues. This review aims to encourage new concepts and testable hypotheses about the two-way interactions between circadian clocks and ECM in the context of aging.