Verduijn Joost, Coutant Kelly, Fane Mitchell E, Galluzzi Lorenzo
Cancer Signaling and Microenvironment Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
Cell Death Differ. 2025 Jun 23. doi: 10.1038/s41418-025-01535-2.
Along with organismal aging, multiple compartments of the immune system undergo a progressive functional degeneration that may contribute to - or at least allow for - disease, a scenario that is commonly known as "immunosenescence". While not all immune cell populations suffer from organismal aging through similar mechanisms, immunosenescence appears to involve numerical alterations in specific immune cell types that - at least in some settings - result from the unscheduled activation of regulated cell death (RCD), often along with unbalanced hematopoietic output downstream of thymic involution and bone marrow defects. Here, we critically discuss core RCD mechanisms including apoptosis, necroptosis, ferroptosis, pyroptosis and NETosis as key regulators of global immune homeostasis in the context of immunosenescence.
随着机体衰老，免疫系统的多个部分会逐渐发生功能退化，这可能会导致疾病，或者至少为疾病的发生创造条件，这种情况通常被称为“免疫衰老”。虽然并非所有免疫细胞群体都通过相似的机制受到机体衰老的影响，但免疫衰老似乎涉及特定免疫细胞类型的数量变化，至少在某些情况下，这些变化是由程序性细胞死亡（RCD）的非计划性激活导致的，通常还伴随着胸腺退化和骨髓缺陷下游造血输出的失衡。在此，我们批判性地讨论了核心RCD机制，包括凋亡、坏死性凋亡、铁死亡、焦亡和中性粒细胞胞外陷阱形成，这些机制在免疫衰老的背景下是全球免疫稳态的关键调节因子。
