Ageing is associated with diminished apoptotic cell clearance in vivo
Ageing is associated with diminished apoptotic cell clearance in vivo
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DOI：
10.1111/j.1365-2249.2008.03658.x
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发表时间：
2008-06-01
影响因子：
4.6
通讯作者：
Walsh, K.
中科院分区：
文献类型：
--
作者：
Aprahamian, T.;Takemura, Y.;Walsh, K.
衰老导致免疫系统功能障碍和自身抗体的积累。由于凋亡细胞的快速吞噬清除是防止自身免疫发展所必需的，我们使用两种独立的测定法检查了年轻和老年小鼠中凋亡物质的相对清除率。首先，发现2岁的小鼠在紫外线照射皮肤后清除凋亡角质形成细胞的能力受损。其次，与8周龄小鼠相比，老年小鼠体内暴露于凋亡Jurkat T细胞的腹腔巨噬细胞的吞噬活性降低。与这些发现一致，老年小鼠表现出自身免疫性体征，出现抗核抗体和肾小球大小增加以及肾小球内补体沉积。体外试验表明，与用年轻小鼠血清处理的巨噬细胞相比，用老年小鼠血清预处理的巨噬细胞吞噬凋亡小体的能力降低。这些数据表明，衰老过程伴随着清除凋亡碎片的能力下降。这种凋亡碎片的积累可能导致老年生物体中发生的免疫系统功能障碍。
Ageing leads to immune system dysfunction and the accumulation of autoantibodies. Because the rapid phagocytic clearance of apoptotic cells is required to prevent the development of autoimmunity, we examined the relative clearance of apoptotic material in young and aged mice using two independent assays. First, 2-year-old mice were found to be impaired in their ability to clear apoptotic keratinocytes following ultraviolet irradiation of the skin. Secondly, peritoneal macrophages exposed to apoptotic Jurkat T cells in vivo displayed diminished phagocytic activity in aged mice compared with 8-week-old mice. Consistent with these findings, aged mice exhibited signs of autoimmunity with the appearance of anti-nuclear antibodies and increased kidney glomerular size as well as complement deposits within the glomeruli. In vitro assays revealed that the pretreatment of macrophages with the serum from aged mice led to a reduction in their ability to phagocytose apoptotic bodies compared with macrophages treated with serum from young mice. These data show that the ageing process is accompanied by a diminished ability to clear apoptotic debris. This accumulation of apoptotic debris could contribute to immune system dysfunction that occurs in aged organisms.