Cellular Senescence: From Mechanisms to Current Biomarkers and Senotherapies.

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Vasco Lucas, Cláudia Cavadas, Célia Alexandra Aveleira
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引用次数: 7

Abstract

An increase in life expectancy in developed countries has led to a surge of chronic aging-related diseases. In the last few decades, several studies have provided evidence of the prominent role of cellular senescence in many of these pathologies. Key traits of senescent cells include cell cycle arrest, apoptosis resistance, and secretome shift to senescence-associated secretory phenotype resulting in increased secretion of various intermediate bioactive factors important for senescence pathophysiology. However, cellular senescence is a highly phenotypically heterogeneous process, hindering the discovery of totally specific and accurate biomarkers. Also, strategies to prevent the pathologic effect of senescent cell accumulation during aging by impairing senescence onset or promoting senescent cell clearance have shown great potential during in vivo studies, and some are already in early stages of clinical translation. The adaptability of these senotherapeutic approaches to human application has been questioned due to the lack of proper senescence targeting and senescence involvement in important physiologic functions. In this review, we explore the heterogeneous phenotype of senescent cells and its influence on the expression of biomarkers currently used for senescence detection. We also discuss the current evidence regarding the efficacy, reliability, development stage, and potential for human applicability of the main existing senotherapeutic strategies. SIGNIFICANCE STATEMENT: This paper is an extensive review of what is currently known about the complex process of cellular senescence and explores its most defining features. The main body of the discussion focuses on how the multifeature fluctuation of the senescence phenotype and the physiological role of cellular senescence have both caused a limitation in the search for truly reliable senescence biomarkers and the progression in the development of senotherapies.

Abstract Image

细胞衰老:从机制到当前的生物标志物和衰老疗法。
发达国家预期寿命的增加导致与衰老有关的慢性疾病激增。在过去的几十年里,一些研究已经提供了细胞衰老在许多这些病理中的突出作用的证据。衰老细胞的关键特征包括细胞周期阻滞、细胞凋亡抵抗和分泌组向衰老相关分泌表型的转变,导致各种对衰老病理生理重要的中间生物活性因子的分泌增加。然而,细胞衰老是一个高度表型异质性的过程,阻碍了完全特异性和准确的生物标志物的发现。此外,通过抑制衰老发生或促进衰老细胞清除来预防衰老过程中衰老细胞积累的病理效应的策略在体内研究中显示出了巨大的潜力,有些已经处于临床转化的早期阶段。由于缺乏适当的衰老靶向和衰老参与重要的生理功能,这些衰老治疗方法对人类应用的适应性受到质疑。在这篇综述中,我们探讨了衰老细胞的异质性表型及其对目前用于衰老检测的生物标志物表达的影响。我们还讨论了目前关于现有主要老年治疗策略的有效性、可靠性、发展阶段和人类适用性的证据。意义声明:本文对目前已知的细胞衰老的复杂过程进行了广泛的回顾,并探讨了其最明确的特征。讨论的主体集中在衰老表型的多特征波动和细胞衰老的生理作用如何导致寻找真正可靠的衰老生物标志物和衰老治疗发展的进展受到限制。
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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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