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.

中文翻译：

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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延长导致与衰老相关的慢性疾病激增。在过去的几十年里，一些研究提供了细胞衰老在许多这些病理学中的突出作用的证据。衰老细胞的关键特征包括细胞周期停滞、细胞凋亡抗性和分泌组向衰老相关分泌表型的转变，从而导致对衰老病理生理学很重要的各种中间生物活性因子的分泌增加。然而，细胞衰老是一个表型高度异质的过程，阻碍了完全特异性和准确的生物标志物的发现。还，通过削弱衰老开始或促进衰老细胞清除来防止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。我们还讨论了有关现有主要衰老治疗策略的功效、可靠性、发展阶段和人类适用性潜力的当前证据。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。我们还讨论了有关现有主要衰老治疗策略的功效、可靠性、发展阶段和人类适用性潜力的当前证据。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。我们还讨论了有关现有主要衰老治疗策略的功效、可靠性、发展阶段和人类适用性潜力的当前证据。我们探讨了衰老细胞的异质表型及其对目前用于衰老检测的生物标志物表达的影响。我们还讨论了有关现有主要衰老治疗策略的功效、可靠性、发展阶段和人类适用性潜力的当前证据。我们探讨了衰老细胞的异质表型及其对目前用于衰老检测的生物标志物表达的影响。我们还讨论了有关现有主要衰老治疗策略的功效、可靠性、发展阶段和人类适用性潜力的当前证据。