Ye Jiayu, Melam Anupama, Stewart Sheila A
Department of Cell Biology & Physiology, Washington University School of Medicine, St. Louis, MO, USA.
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
Nat Rev Cancer. 2025 Aug 4. doi: 10.1038/s41568-025-00840-9.
Ageing is a process characterized by a wide array of cellular and systemic changes that together increase the risk of developing cancer. While cell-autonomous mutations within incipient tumour cells are important, age-related changes in the microenvironment are critical partners in the transformation process and response to therapy. However, aspects of ageing that are important and the degree to which they contribute to cancer remain obscure. One of the factors that impacts ageing is increased cellular senescence but it is important to note that ageing and cellular senescence are not synonymous. We highlight open questions, including if senescent cells have phenotypically distinct impacts in aged versus young tissue, or if it is the cell type that dictates the impact of senescence on tissue homeostasis and disease. Finally, it is probable that our current definition of cellular senescence encompasses more than one mechanistically distinct cellular state; thus, we highlight phenotypic differences that have been noted across cell types and tissues of origin. This Review focuses on the role that senescent stromal cells have in cancer, with a particular emphasis on fibroblasts given the amount of work that has focused on them.
衰老过程的特征是一系列细胞和全身变化，这些变化共同增加了患癌风险。虽然初始肿瘤细胞内的细胞自主突变很重要，但微环境中与年龄相关的变化是肿瘤转化过程和对治疗反应的关键因素。然而，衰老的重要方面及其对癌症的影响程度仍不清楚。影响衰老的因素之一是细胞衰老增加，但需要注意的是，衰老和细胞衰老并非同义词。我们强调了一些悬而未决的问题，包括衰老细胞在老年组织和年轻组织中是否具有表型上不同的影响，或者是否是细胞类型决定了衰老对组织稳态和疾病的影响。最后，我们目前对细胞衰老的定义可能涵盖了不止一种机制上不同的细胞状态；因此，我们强调了在不同细胞类型和组织来源中所观察到的表型差异。本综述重点关注衰老的基质细胞在癌症中的作用，鉴于针对成纤维细胞的研究工作很多，因此特别强调了成纤维细胞。
