Centre for Inflammatory Disease, Imperial College London, Hammersmith Hospital, London, UK.
Medical Research Council London Institute of Medical Sciences, London, UK.
J Cell Biol. 2021 Feb 1;220(2). doi: 10.1083/jcb.202010162.
Senescence is a cellular program that prevents the replication of old, damaged, or cancerous cells. Senescent cells become growth arrested and undergo changes in their morphology, chromatin organization, and metabolism, and produce a bioactive secretome. This secretome, the senescence-associated secretory phenotype (SASP), mediates many of the pathophysiological effects associated with senescent cells, for example, recruiting and activating immune cells such as macrophages. The relation between senescent cells and macrophages is intriguing: senescent cells recruit macrophages, can induce them to undergo senescence, or can influence their polarization. Senescent cells and macrophages share multiple phenotypic characteristics; both have a high secretory status, increased lysosome numbers, or the ability to activate the inflammasome. Senescent cells accumulate during aging and disease, and killing them results in widespread benefits. Here we discuss similarities between senescent cells and macrophages and interpret the latest developments in macrophage biology to understand the molecular mechanisms of cellular senescence. We describe evidence and effects of senescence in macrophages and speculate on the ontogeny of the senescent-like state in macrophages. Finally, we examine the macrophage-senescent cell interplay and its impact on macrophage effector functions during inflammatory conditions and in the tumor microenvironment.
衰老是一种细胞程序性死亡，可防止衰老、受损或癌变细胞的复制。衰老细胞生长停滞，并在形态、染色质组织和代谢方面发生变化，同时产生具有生物活性的分泌组。该分泌组，即衰老相关分泌表型（SASP），介导了与衰老细胞相关的许多病理生理效应，例如招募和激活巨噬细胞等免疫细胞。衰老细胞与巨噬细胞之间的关系很有趣：衰老细胞招募巨噬细胞，可诱导其衰老，或影响其极化。衰老细胞和巨噬细胞具有多种表型特征；两者都具有高分泌状态、增加的溶酶体数量或激活炎症小体的能力。衰老细胞在衰老和疾病过程中积累，清除它们会带来广泛的益处。在这里，我们讨论了衰老细胞和巨噬细胞之间的相似性，并解释了巨噬细胞生物学的最新进展，以了解细胞衰老的分子机制。我们描述了巨噬细胞中衰老的证据和影响，并推测了巨噬细胞中衰老样状态的发生。最后，我们研究了巨噬细胞-衰老细胞的相互作用及其对炎症条件下和肿瘤微环境中巨噬细胞效应功能的影响。
