Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.
Metabolic Damage and Premature Thymus Aging Caused by Stromal Catalase Deficiency.
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DOI：
10.1016/j.celrep.2015.07.008
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发表时间：
2015-08-18
期刊：
影响因子：
8.8
通讯作者：
Petrie HT
中科院分区：
文献类型：
--
作者：
Griffith AV;Venables T;Shi J;Farr A;van Remmen H;Szweda L;Fallahi M;Rabinovitch P;Petrie HT
T淋巴细胞是免疫的基本介质，由胸腺按其大小比例产生。随着年龄的增长，胸腺迅速萎缩，导致新T细胞产生的进行性减少。这种减少的输出通过复制现有的T细胞来补偿，但它导致记忆T细胞逐渐占主导地位，并降低对新病原体或疫苗的反应能力。在这里，我们表明，加速和不可逆的胸腺萎缩的结果从基质中缺乏还原酶过氧化氢酶，导致有氧代谢产生的过氧化氢的损害增加。基质细胞中过氧化氢酶的遗传互补减少了萎缩，化学抗氧化剂也是如此，因此提供了抗氧化剂，代谢和正常免疫功能之间的机械联系。我们认为，不可逆的胸腺萎缩代表了一个传统的老化过程，是加速基质过氧化氢酶缺乏的背景下，强烈的合成代谢（淋巴）的环境。
T lymphocytes are essential mediators of immunity that are produced by the thymus in proportion to its size. The thymus atrophies rapidly with age, resulting in progressive diminution of new T cell production. This decreased output is compensated by duplication of existing T cells, but it results in gradual dominance by memory T cells and decreased ability to respond to new pathogens or vaccines. Here, we show that accelerated and irreversible thymic atrophy results from stromal deficiency in the reducing enzyme catalase, leading to increased damage by hydrogen peroxide generated by aerobic metabolism. Genetic complementation of catalase in stromal cells diminished atrophy, as did chemical antioxidants, thus providing a mechanistic link between antioxidants, metabolism, and normal immune function. We propose that irreversible thymic atrophy represents a conventional aging process that is accelerated by stromal catalase deficiency in the context of an intensely anabolic (lymphoid) environment.