The mitochondrial theory of aging: Is the culprit a faulty disposal system rather than indigenous mitochondrial alterations?
The mitochondrial theory of aging: Is the culprit a faulty disposal system rather than indigenous mitochondrial alterations?
复制标题
DOI：
10.1016/s0531-5565(99)00010-8
复制
发表时间：
1999-08-01
影响因子：
3.9
通讯作者：
Gershon, D
中科院分区：
文献类型：
--
作者：
Gershon, D
线粒体损伤和线粒体在细胞中的比例随着年龄的增长而增加。根据衰老的线粒体理论，这种现象主要是由于氧化损伤造成的，是衰老的主要(有些人认为是主要的)决定因素。简单地说，这一现象在衰老过程中扮演的角色并不是唯一至关重要的。它还将争辩说，主要是基于理论依据(由于缺乏足够的当前信息)，受影响线粒体降解减少的积累是由于羟基自由基的产生减少所致，正如Aubrey和De Grey(1997)所建议的并由科瓦尔德(在本期中)扩展的那样。似乎更有可能的是，在衰老有机体的细胞中，虚弱线粒体的吞噬溶酶体处理系统发生了很大的变化。此外，鉴于受损的线粒体在细胞凋亡的初始步骤中的重要作用，以及缺乏证据表明衰老个体的细胞大量凋亡，存在的损害可能比线粒体衰老理论预期的要轻。为了更好地理解本文中提出的论点，本文包括了关于线粒体生物学的简要基本概述。同时，对Aubrey和De Grey(1997)和科瓦尔德(1999)提出的假说提出了实验验证的建议。(C)1999 Elsevier Science Inc.保留所有权利。
Mitochondrial damage and the proportion of effete mitochondria in cells increase with age. According to the mitochondrial theory of aging, this phenomenon is mostly due to oxidative damage and is a major (and, some argue, the main) determinant of aging. It will be argued briefly that this phenomenon plays a role that is not exclusively crucial in aging. It will also be contended, essentially on theoretical grounds (for lack of sufficient current information), that there is low probability that the accumulation of reduced degradation of affected mitochondria is due to diminished production of hydroxyl radicals, as suggested by Aubrey and de Grey (1997) and expanded by Kowald (in this issue). What seems more likely is that the phagolysosomal disposal system of effete mitochondria is considerably altered in cells of aging organisms. Also, in view of the significant role of damaged mitochondria in the initial steps in apoptosis and the lack of evidence of massive apoptosis of cells in senescent individuals, the damage that exists may be milder than anticipated by the mitochondrial theory of aging. A brief fundamental summary on the biology of mitochondria is included for the sake of better understanding the arguments presented in this article. Also, suggestions are made for experimental testing of the hypotheses presented by Aubrey and de Grey (1997) and Kowald (1999). (C) 1999 Elsevier Science Inc. All rights reserved.