Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Research Institute of Stomatology & Stomatological Hospital and Dental School, Tongji University, Shanghai, China.
Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Research Institute of Stomatology & Stomatological Hospital and Dental School, Tongji University, Shanghai, China.
Mol Cells. 2024 Nov;47(11):100113. doi: 10.1016/j.mocell.2024.100113. Epub 2024 Sep 19.
During the aging process or disease progression, normal cells and tissues in the body undergo various stresses, leading to cell damage and the need for repair, adaptation, apoptosis, or defense responses. Cellular senescence is a key player in this process, influencing the rate of aging and disease progression. It can be triggered by different stress factors, resulting in irreversible cell cycle arrest and functional decline. Senescent cells often show high expression of cell cycle factors such as p21 and p16, which are involved in cell cycle arrest. p16 has long been recognized as a significant marker of aging. Recent evidence suggests that p21 cells and p16 cells represent distinct cell populations in terms of cell type, tissue location, accumulation kinetics, and physiological functions. This article focuses on recent advancements in understanding p21-dependent cellular senescence. It starts by providing an overview of the role of p21 in 3 primary cellular senescence phenotypes where it plays a crucial role. It then delves into the pathogenesis of diseases closely linked to p21-dependent cellular senescence, particularly metabolic disorders and cardiovascular diseases. The article also discusses progress in p21-related animal models and outlines strategies for utilizing p21 to intervene in cellular senescence by delaying aging, eliminating senescent cells, and rejuvenating senescent cells. This review systematically examines the pathogenesis of p21-dependent cellular senescence, emphasizing its importance in studying aging heterogeneity and developing new senolytic therapies. It aims to stimulate future research on leveraging p21 to enhance the characteristics of senescent cells, allowing more precise methods for eliminating harmful senescent cells at the right time, thereby delaying aging and potentially achieving rejuvenation.
在衰老过程或疾病进展中，体内的正常细胞和组织会经历各种应激，导致细胞损伤和需要修复、适应、凋亡或防御反应。细胞衰老在这个过程中是一个关键因素，影响着衰老和疾病进展的速度。它可以由不同的应激因素触发，导致细胞周期不可逆停滞和功能下降。衰老细胞通常表现出高水平的细胞周期因子，如 p21 和 p16，这些因子参与细胞周期停滞。p16 长期以来一直被认为是衰老的重要标志物。最近的证据表明，p21 细胞和 p16 细胞在细胞类型、组织位置、积累动力学和生理功能方面代表了不同的细胞群体。本文重点介绍了对 p21 依赖性细胞衰老的最新认识进展。它首先概述了 p21 在三种主要的细胞衰老表型中的作用，p21 在这些表型中起着至关重要的作用。然后，它深入探讨了与 p21 依赖性细胞衰老密切相关的疾病的发病机制，特别是代谢紊乱和心血管疾病。本文还讨论了与 p21 相关的动物模型的进展，并概述了利用 p21 干预细胞衰老的策略，包括延缓衰老、消除衰老细胞和使衰老细胞年轻化。本综述系统地研究了 p21 依赖性细胞衰老的发病机制，强调了其在研究衰老异质性和开发新的衰老细胞清除疗法方面的重要性。它旨在激发未来对利用 p21 增强衰老细胞特征的研究，从而更精确地在适当的时间消除有害的衰老细胞，延缓衰老并可能实现年轻化。
