Shaanxi Key Laboratory of Brain Disorders, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.
J Gerontol A Biol Sci Med Sci. 2022 Nov 21;77(11):2207-2218. doi: 10.1093/gerona/glac097.
Senescent cells express and secrete a variety of extracellular modulators that include cytokines, chemokines, proteases, growth factors, and some enzymes associated with extracellular matrix remodeling, defined as the senescence-associated secretory phenotype (SASP). SASP reinforces senescent cell cycle arrest, stimulates and recruits immune cells for immune-mediated clearance of potentially tumorigenic cells, limits or induces fibrosis, and promotes wound healing and tissue regeneration. On the other hand, SASP mediates chronic inflammation leading to the destruction of tissue structure and function and stimulating the growth and survival of tumor cells. SASP is highly heterogeneous and the role of SASP depends on the context. The regulation of SASP occurs at multiple levels including chromatin remodeling, transcription, mRNA translation, intracellular trafficking, and secretion. Several SASP modulators have already been identified setting the stage for future research on their clinical applications. In this review, we summarize in detail the potential signaling pathways that trigger and regulate SASP production during aging and senescence.
衰老细胞表达和分泌多种细胞外调节剂，包括细胞因子、趋化因子、蛋白酶、生长因子和一些与细胞外基质重塑相关的酶，这些被定义为衰老相关分泌表型 (SASP)。SASP 增强衰老细胞的细胞周期停滞，刺激并招募免疫细胞进行免疫介导的潜在致瘤细胞清除，限制或诱导纤维化，并促进伤口愈合和组织再生。另一方面，SASP 介导慢性炎症，导致组织结构和功能的破坏，并刺激肿瘤细胞的生长和存活。SASP 具有高度异质性，其作用取决于具体情况。SASP 的调控发生在多个层面，包括染色质重塑、转录、mRNA 翻译、细胞内运输和分泌。已经鉴定出几种 SASP 调节剂，为它们的临床应用的未来研究奠定了基础。在这篇综述中，我们详细总结了在衰老和衰老过程中触发和调节 SASP 产生的潜在信号通路。
