Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, Belgium.
University of Lille, CNRS, Inserm, Pasteur Institute of Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, 59000 Lille, France.
Int J Mol Sci. 2023 Jun 28;24(13):10788. doi: 10.3390/ijms241310788.
Cellular senescence is a complex cell state that can occur during physiological ageing or after exposure to stress signals, regardless of age. It is a dynamic process that continuously evolves in a context-dependent manner. Senescent cells interact with their microenvironment by producing a heterogenous and plastic secretome referred to as the senescence-associated secretory phenotype (SASP). Hence, understanding the cross-talk between SASP and the microenvironment can be challenging due to the complexity of signal exchanges. In this review, we first aim to update the definition of senescence and its associated biomarkers from its discovery to the present day. We detail the regulatory mechanisms involved in the expression of SASP at multiple levels and develop how SASP can orchestrate microenvironment modifications, by focusing on extracellular matrix modifications, neighboring cells' fate, and intercellular communications. We present hypotheses on how these microenvironmental events may affect dynamic changes in SASP composition in return. Finally, we discuss the various existing approaches to targeting SASP and clarify what is currently known about the biological effects of these modified SASPs on the cellular environment.
细胞衰老（cellular senescence）是一种复杂的细胞状态，它可以在生理衰老或暴露于应激信号时发生，而与年龄无关。它是一个动态过程，以依赖于上下文的方式不断演变。衰老细胞通过产生一种异质和可塑性的分泌组，即衰老相关分泌表型（SASP），与微环境相互作用。因此，由于信号交换的复杂性，理解 SASP 与微环境之间的串扰可能具有挑战性。在这篇综述中，我们首先旨在更新从发现至今衰老及其相关生物标志物的定义。我们详细描述了 SASP 在多个水平上表达所涉及的调节机制，并通过关注细胞外基质的修饰、相邻细胞的命运和细胞间通讯，研究了 SASP 如何协调微环境的修饰。我们提出了关于这些微环境事件如何可能影响 SASP 组成的动态变化的假设。最后，我们讨论了靶向 SASP 的各种现有方法，并阐明了目前已知的这些修饰的 SASP 对细胞环境的生物学效应。
