Changes in primary lymphoid organs with aging.
Changes in primary lymphoid organs with aging.
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DOI：
10.1016/j.smim.2012.04.005
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发表时间：
2012-10
影响因子：
7.8
通讯作者：
Sempowski GD
中科院分区：
文献类型：
--
作者：
Chinn IK;Blackburn CC;Manley NR;Sempowski GD
衰老与免疫功能下降有关，导致老年人发病率和死亡率增加。免疫衰老伴随着两个主要淋巴器官（骨髓和胸腺）的年龄相关变化，导致B和T淋巴细胞的产生和功能降低。在骨髓中，随着年龄的增长，造血干细胞表现出降低的自我更新潜力，增加的骨髓生成倾向，以及减少的淋巴细胞产生。这些老化的功能性后遗症部分是由氧化应激增加、炎症、脂肪细胞分化和缺氧成骨细胞龛破坏引起的。在胸腺中，衰老与组织退化有关，表现为胸腺上皮细胞结构的紊乱和肥胖增加。这种失调与基质-胸腺细胞“交叉对话”的丧失相关，导致幼稚T细胞的输出减少。越来越多的证据表明，随着衰老，胸腺炎症、全身应激、局部Foxn 1和角质形成细胞生长因子表达以及性类固醇水平在积极推动胸腺退化和整个生命周期的整体适应性免疫衰老方面发挥着关键作用。随着对介导骨髓和胸腺随衰老退化的复杂机制和途径的更好理解，开发安全有效的干预措施以预防或恢复随衰老而丧失的免疫功能的潜力增加。
Aging is associated with decreased immune function that leads to increased morbidity and mortality in the elderly. Immune senescence is accompanied by age-related changes in two primary lymphoid organs, bone marrow and thymus, that result in decreased production and function of B and T lymphocytes. In bone marrow, hematopoietic stem cells exhibit reduced self-renewal potential, increased skewing toward myelopoiesis, and decreased production of lymphocytes with aging. These functional sequelae of aging are caused in part by increased oxidative stress, inflammation, adipocyte differentiation, and disruption of hypoxic osteoblastic niches. In thymus, aging is associated with tissue involution, exhibited by a disorganization of the thymic epithelial cell architecture and increased adiposity. This dysregulation correlates with a loss of stroma-thymocyte ‘cross-talk’, resulting in decreased export of naïve T cells. Mounting evidence argues that with aging, thymic inflammation, systemic stress, local Foxn1 and keratinocyte growth factor expression, and sex steroid levels play critical roles in actively driving thymic involution and overall adaptive immune senescence across the lifespan. With a better understanding of the complex mechanisms and pathways that mediate bone marrow and thymus involution with aging, potential increases for the development of safe and effective interventions to prevent or restore loss of immune function with aging.
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DOI：
10.1073/pnas.93.12.5742
发表时间：
1996-06-11
影响因子：
11.1
作者：
Blackburn, CC;Augustine, CL;Morahan, G
通讯作者：
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影响因子：
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作者：
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20.3
作者：
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影响因子：
2.6
作者：
Chen, JC;Astle, CM;Harrison, DE
通讯作者：
Harrison, DE
DOI：
10.1073/pnas.0913834107
发表时间：
2010-08-03
影响因子：
11.1
作者：
Coussens, Matthew;Davy, Philip;Allsopp, Richard
通讯作者：
Allsopp, Richard