Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype.
Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype.
复制标题
细胞衰老的机制：细胞周期停滞和衰老相关的分泌表型。
DOI：
10.3389/fcell.2021.645593
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发表时间：
2021
影响因子：
5.5
通讯作者：
Jat P
中科院分区：
文献类型：
--
作者：
Kumari R;Jat P
细胞衰老是一种稳定的细胞周期停滞，可以在正常细胞响应各种内在和外在刺激以及发育信号而触发。衰老被认为是一个高度动态的、多步骤的过程，在此过程中，衰老细胞的特性以一种依赖于环境的方式不断进化和多样化。它与多种细胞和分子变化以及明显的表型改变有关，包括对有丝分裂刺激无反应的稳定增殖阻滞。衰老细胞保持活力，代谢活性发生改变，基因表达发生剧烈变化，并形成复杂的衰老相关分泌表型。细胞衰老会损害组织修复和再生，从而导致衰老。清除衰老细胞可以减轻与年龄相关的组织功能障碍，延长健康寿命。衰老也可以作为一种有效的抗肿瘤机制，通过防止潜在癌细胞的增殖。它是一种细胞程序，就像一把双刃剑，对生物体的健康既有有益的影响，也有有害的影响，被认为是进化拮抗多效性的一个例子。p53/p21WAF1/CIP1和p16INK4A/pRB肿瘤抑制通路的激活在调节衰老中发挥核心作用。一些其他的途径最近被牵连到介导衰老和衰老表型。在这里，我们回顾了细胞衰老和衰老相关的生长停滞的分子机制，特别关注细胞停止分裂的原因、生长停滞的稳定性、高分泌表型以及不同途径是如何整合的。
Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells in response to various intrinsic and extrinsic stimuli, as well as developmental signals. Senescence is considered to be a highly dynamic, multi-step process, during which the properties of senescent cells continuously evolve and diversify in a context dependent manner. It is associated with multiple cellular and molecular changes and distinct phenotypic alterations, including a stable proliferation arrest unresponsive to mitogenic stimuli. Senescent cells remain viable, have alterations in metabolic activity and undergo dramatic changes in gene expression and develop a complex senescence-associated secretory phenotype. Cellular senescence can compromise tissue repair and regeneration, thereby contributing toward aging. Removal of senescent cells can attenuate age-related tissue dysfunction and extend health span. Senescence can also act as a potent anti-tumor mechanism, by preventing proliferation of potentially cancerous cells. It is a cellular program which acts as a double-edged sword, with both beneficial and detrimental effects on the health of the organism, and considered to be an example of evolutionary antagonistic pleiotropy. Activation of the p53/p21WAF1/CIP1 and p16INK4A/pRB tumor suppressor pathways play a central role in regulating senescence. Several other pathways have recently been implicated in mediating senescence and the senescent phenotype. Herein we review the molecular mechanisms that underlie cellular senescence and the senescence associated growth arrest with a particular focus on why cells stop dividing, the stability of the growth arrest, the hypersecretory phenotype and how the different pathways are all integrated.
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影响因子：
64.8
作者：
Baker DJ;Childs BG;Durik M;Wijers ME;Sieben CJ;Zhong J;Saltness RA;Jeganathan KB;Verzosa GC;Pezeshki A;Khazaie K;Miller JD;van Deursen JM
通讯作者：
van Deursen JM
影响因子：
64.8
作者：
Bartkova, Jirina;Rezaei, Nousin;Gorgoulis, Vassilis G.
通讯作者：
Gorgoulis, Vassilis G.
DOI：
10.1038/nri3921
发表时间：
2015-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.5
作者：
Barradas, Marta;Anderton, Emma;Gil, Jesus
通讯作者：
Gil, Jesus
影响因子：
10.5
作者：
Agger, Karl;Cloos, Paul A. C.;Helin, Kristian
通讯作者：
Helin, Kristian