Majewska Julia, Krizhanovsky Valery
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Nat Aging. 2025 Aug;5(8):1415-1424. doi: 10.1038/s43587-025-00910-5. Epub 2025 Aug 14.
Senescent cells are intrinsically immunogenic and can be eliminated by the immune system to facilitate tissue repair and regeneration. However, immune-mediated elimination is compromised with age, causing senescent cell accumulation in tissues, thus limiting healthspan and lifespan and promoting age-related diseases such as cancer. Here, we review how different components of the innate and adaptive immune systems, including natural killer cells, macrophages, neutrophils, dendritic cells, T cells and B cells, target senescent cells and how the intrinsic properties of senescent cells can lead to their escape from surveillance. We also discuss the phenomenon of senescence in immune cells themselves and how this affects the surveillance of senescent and cancerous cells. Finally, we touch on emerging therapeutic strategies to enhance the immunosurveillance of senescent cells, as understanding the molecular basis of senescence immunosurveillance and why its potency fails during aging may offer opportunities to treat senescence-mediated age-associated diseases and tissue dysfunction.
衰老细胞本质上具有免疫原性,可被免疫系统清除以促进组织修复和再生。然而,免疫介导的清除作用会随着年龄增长而受损,导致衰老细胞在组织中积累,从而限制健康寿命和寿命,并促进诸如癌症等与年龄相关的疾病。在此,我们综述先天性和适应性免疫系统的不同组成部分,包括自然杀伤细胞、巨噬细胞、中性粒细胞、树突状细胞、T细胞和B细胞,如何靶向衰老细胞,以及衰老细胞的内在特性如何导致它们逃避监测。我们还讨论免疫细胞自身的衰老现象以及这如何影响对衰老细胞和癌细胞的监测。最后,我们探讨增强对衰老细胞免疫监测的新兴治疗策略,因为了解衰老免疫监测的分子基础以及为何其效力在衰老过程中失效,可能为治疗衰老介导的年龄相关疾病和组织功能障碍提供机会。