Immunology, Microenvironment & Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Immunology, Microenvironment & Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
Trends Cell Biol. 2022 Jun;32(6):513-526. doi: 10.1016/j.tcb.2021.12.003. Epub 2022 Jan 7.
Cellular senescence is a stable cell growth arrest. Senescent cells are metabolically active, as exemplified by the secretion of inflammatory cytokines, chemokines, and growth factors, which is termed senescence-associated secretory phenotype (SASP). The SASP exerts a range of functions in both normal health and pathology, which is possibly best characterized in cancers and physical aging. Recent studies demonstrated that chromatin is instrumental in regulating the SASP both through nuclear transcription and via the innate immune cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in the cytoplasm. Here, we will review these regulatory mechanisms, with an emphasis on most recent developments in the field. We will highlight the challenges and opportunities in developing intervention approaches, such as targeting chromatin regulatory mechanisms, to alter the SASP as an emerging approach to combat cancers and achieve healthy aging.
细胞衰老（Cellular senescence）是一种稳定的细胞生长停滞。衰老细胞具有代谢活性，其表现为炎症细胞因子、趋化因子和生长因子的分泌，这被称为衰老相关分泌表型（Senescence-Associated Secretory Phenotype，SASP）。SASP 在正常健康和病理学中发挥了一系列功能，这在癌症和身体衰老中表现得最为明显。最近的研究表明，染色质通过核转录和细胞质中环鸟苷酸-腺苷酸合酶（cyclic GMP-AMP synthase，cGAS）-干扰素基因刺激物（stimulator of interferon genes，STING）途径在调节 SASP 方面发挥了重要作用。在这里，我们将回顾这些调节机制，并特别强调该领域的最新进展。我们将强调开发干预方法（如靶向染色质调节机制）的挑战和机遇，以改变 SASP，作为一种新兴的抗癌和实现健康衰老的方法。
