A proposed refinement of the mitochondrial free radical theory of aging
A proposed refinement of the mitochondrial free radical theory of aging
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DOI：
10.1002/bies.950190211
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发表时间：
1997-02-01
期刊：
影响因子：
4
通讯作者：
deGrey, ADNJ
中科院分区：
文献类型：
--
作者：
deGrey, ADNJ
近年来，越来越多的证据支持由哈曼首先提出的自由基衰老理论。尽管如此，对细胞屈服于自由基影响的机制的理解仍被证明是难以捉摸的。本文提出了这样一种机制，基于一个先前未被探索的关于突变线粒体DNA增殖的假设：由于影响呼吸链的突变或缺失，呼吸功能降低的线粒体遭受较少的溶酶体降解，因为它们对自身膜造成自由基损伤的速度较慢。一旦这种突变发生在非分裂细胞的线粒体中，因此，携带它的线粒体将迅速填充该细胞，从而破坏细胞的呼吸能力。经历这种转变的细胞的积累导致了机体水平的衰老。讨论了假设与已知事实的一致性，并提出了技术上可行的测试，提出了提出的机制及其对哺乳动物衰老的总体贡献。
Over recent years, evidence has been accumulating in favour of the free radical theory of aging, first proposed by Harman. Despite this, an understanding of the mechanism by which cells might succumb to the effects of free radicals has proved elusive. This paper proposes such a mechanism, based on a previously unexplored hypothesis for the proliferation of mutant mitochondrial DNA: that mitochondria with reduced respiratory function, due to a mutation or deletion affecting the respiratory chain, suffer less frequent lysosomal degradation, because they inflict free radical damage more slowly on their own membranes. Once such a mutation occurs in a mitochondrion of a non-dividing cell, therefore, mitochondria carrying it will rapidly populate that cell, thereby destroying the cell's respiratory capability. The accumulation of cells that have undergone this transition results in aging at the organismal level. The consistency of the hypothesis with known facts is discussed, and technically feasible tests are suggested, of both the proposed mechanism and its overall contribution to mammalian aging.