Centre for Biological Engineering, Wolfson School of Manufacturing and Mechanical, Engineering, Holywell Park, Loughborough University, LE11 3TU.
Centre for Biological Engineering, Wolfson School of Manufacturing and Mechanical, Engineering, Holywell Park, Loughborough University, LE11 3TU.
Ageing Res Rev. 2018 May;43:17-25. doi: 10.1016/j.arr.2018.02.001. Epub 2018 Feb 7.
In response to persistent DNA damage, induction into cell senescence promotes an immunogenic program which facilitates immune clearance of these damaged cells. Under physiological conditions, senescent cells can activate both innate and adaptive immune responses, functioning to maintain tissue homeostasis. In addition, emerging findings suggest that programmed induction of cell senescence may be important for regulating reproductive processes, partly facilitated by immune clearance. However, likely owing to ageing of the immune system, a failure to eliminate senescent cells can contribute to their persistence in tissues, leading to the development and progression of age-related diseases. Such immune failure may in part be due to activation of the senescence program in immune cells, leading to their dysfunction. Furthermore, senescent cells under certain biological contexts have been shown to instead promote immune suppression, a response that may reflect differences between an acute verses chronic senescent phenotype. In this review, we provide an overview of the research to date concerning senescence immunosurviellance, including a focused discussion on the mechanisms by which macrophages may recognise senescent cells. Senescence immunotherapy strategies as an alternative to senolytics for the removal of senescent cells will also be discussed.
针对持续的 DNA 损伤，诱导细胞衰老会促进免疫原性程序，从而促进这些受损细胞的免疫清除。在生理条件下，衰老细胞可以激活先天免疫和适应性免疫反应，从而维持组织内环境稳定。此外，新的研究结果表明，程序性诱导细胞衰老可能对调节生殖过程很重要，部分原因是通过免疫清除来实现。然而，由于免疫系统的衰老，未能清除衰老细胞可能导致其在组织中持续存在，从而导致与年龄相关的疾病的发展和进展。这种免疫失败可能部分归因于免疫细胞中衰老程序的激活，导致其功能障碍。此外，在某些生物学环境下，衰老细胞反而会促进免疫抑制，这种反应可能反映了急性与慢性衰老表型之间的差异。在这篇综述中，我们概述了迄今为止有关衰老免疫监视的研究，包括重点讨论了巨噬细胞识别衰老细胞的机制。我们还将讨论衰老免疫疗法策略作为衰老细胞清除的替代方案，即衰老抑制剂。
