Bascom Palmer Eye Institute, Neuroscience Program, Dept. of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Ageing Res Rev. 2013 Sep;12(4):1005-12. doi: 10.1016/j.arr.2013.05.006. Epub 2013 Jun 4.
Immunologically-silent phagocytosis of apoptotic cells is critical to maintaining tissue homeostasis and innate immune balance. Aged phagocytes reduce their functional activity, leading to accumulation of unphagocytosed debris, chronic sterile inflammation and exacerbation of tissue aging and damage. Macrophage dysfunction plays an important role in immunosenescence. Microglial dysfunction has been linked to age-dependent neurodegenerations. Retinal pigment epithelial (RPE) cell dysfunction has been implicated in the pathogenesis of age-related macular degeneration (AMD). Despite several reports on the characterization of aged phagocytes, the role of phagocyte dysfunction in tissue aging and degeneration is yet to be fully appreciated. Lack of knowledge of molecular mechanisms by which aging reduces phagocyte function has hindered our capability to exploit the therapeutic potentials of phagocytosis for prevention or delay of tissue degeneration. This review summarizes our current knowledge of phagocyte dysfunction in aged tissues and discusses possible links to age-related diseases. We highlight the challenges to decipher the molecular mechanisms, present new research approaches and envisage future strategies to prevent phagocyte dysfunction, tissue aging and degeneration.
免疫静默吞噬凋亡细胞对于维持组织内稳态和固有免疫平衡至关重要。衰老的吞噬细胞功能活性降低，导致未被吞噬的碎片积累、慢性无菌性炎症以及组织衰老和损伤加剧。巨噬细胞功能障碍在免疫衰老中起重要作用。小胶质细胞功能障碍与年龄相关性神经退行性变有关。视网膜色素上皮 (RPE) 细胞功能障碍与年龄相关性黄斑变性 (AMD) 的发病机制有关。尽管有几项关于衰老吞噬细胞特征的报道，但吞噬细胞功能障碍在组织衰老和退化中的作用尚未得到充分认识。由于缺乏有关衰老降低吞噬细胞功能的分子机制的知识，我们利用吞噬作用的治疗潜力来预防或延缓组织退化的能力受到了限制。本综述总结了我们目前对衰老组织中吞噬细胞功能障碍的认识，并讨论了与年龄相关疾病的可能联系。我们强调了解密分子机制的挑战，提出了新的研究方法，并设想了未来预防吞噬细胞功能障碍、组织衰老和退化的策略。
