MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Wolfson Drive, Birmingham, B15 2TT, United Kingdom.
MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Wolfson Drive, Birmingham, B15 2TT, United Kingdom; National Institute for Health Research Birmingham Biomedical Research Centre, University Hospital Birmingham NHS Foundation Trust and University of Birmingham, Birmingham, United Kingdom.
Pharmacol Res. 2021 Jan;163:105323. doi: 10.1016/j.phrs.2020.105323. Epub 2020 Dec 1.
Ageing is a universal biological phenomenon that is accompanied by the development of chronic, low-grade inflammation and remodelling of the immune system resulting in compromised immune function. In this review, we explore how the trafficking of innate and adaptive immune cells under homeostatic and inflammatory conditions is dysregulated in ageing. We particularly highlight the age-related changes in the expression of adhesion molecules and chemokine receptor/ligands, and the accumulation of senescent cells that drive modulated leukocyte trafficking. These age-related changes to leukocyte trafficking are multifactorial and specific to leukocyte subset, tissue, type of vascular bed, and inflammatory status. However, dysregulated leukocyte trafficking ultimately affects immune responses in older adults. We therefore go on to discuss approved drugs, including anti-integrins, anti-chemokines and statins, as well as novel therapeutics that may be used to target dysregulated leukocyte trafficking in ageing, improve immune responses and delay the onset of age-related diseases.
衰老是一种普遍的生物现象，伴随着慢性、低水平炎症的发展和免疫系统的重塑，导致免疫功能受损。在这篇综述中，我们探讨了在稳态和炎症条件下，先天和适应性免疫细胞的迁移如何在衰老过程中失调。我们特别强调了与年龄相关的粘附分子和趋化因子受体/配体表达的变化，以及衰老细胞的积累，这些变化驱动了白细胞迁移的调节。白细胞迁移的这些与年龄相关的变化是多因素的，并且特定于白细胞亚群、组织、血管床类型和炎症状态。然而，白细胞迁移的失调最终会影响老年人的免疫反应。因此，我们接着讨论了已批准的药物，包括抗整合素、抗趋化因子和他汀类药物，以及可能用于靶向衰老过程中白细胞迁移失调、改善免疫反应和延缓与年龄相关疾病发生的新型治疗方法。
