Austad Steven N
Department of Biology, University of Alabama at Birmingham, 1720 Second Avenue South, CH 464, Birmingham, AL 35294-1170, USA.
Integr Comp Biol. 2018 Sep 1;58(3):559-566. doi: 10.1093/icb/icy068.
The mitochondrial hypothesis of aging evolved from the rate-of-living theory. That theory posited that the rate of aging was largely determined by the rate of energy expenditure. The mechanistic link between energy expenditure and aging was hypothesized to be oxidative stress. As both energy expenditure and reactive oxygen species (ROS) centered on the mitochondria that organelle became a central focus of aging research. Until about the turn of the 21st century available evidence largely supported the efficiency of mitochondrial function as a key contributor to aging. However as methods for investigating mitochondrial oxidant production and tissue level oxidative damage improved, evidentiary support for the theory weakened. Recently, direct disruption of mitochondrial function has been shown not to shorten life or health as expected, but in many cases in multiple laboratory species disrupted mitochondrial function has lengthened life, sometimes without apparent tradeoffs. Does this mean that mitochondrial function plays no role in aging as had been posited for many years? One key consideration is that experiments under laboratory conditions can be misleading about physiological processes that occur in the uncertain conditions of nature. Before we discard the mitochondrial hypothesis of aging, more field experiments targeted at that hypothesis need to be performed. Fortunately, emerging technology is making such experiment more possible than ever before.
衰老的线粒体假说源于生命速率理论。该理论假定,衰老速率在很大程度上由能量消耗速率决定。能量消耗与衰老之间的机制联系被假定为氧化应激。由于能量消耗和活性氧(ROS)都以线粒体为中心,该细胞器成为衰老研究的核心焦点。直到21世纪之交,现有证据在很大程度上支持线粒体功能效率是衰老的关键因素这一观点。然而,随着研究线粒体氧化剂产生和组织水平氧化损伤的方法得到改进,该理论的证据支持减弱。最近,线粒体功能的直接破坏并未如预期那样缩短寿命或损害健康,而是在许多情况下,在多个实验室物种中,线粒体功能破坏延长了寿命,有时还没有明显的权衡。这是否意味着线粒体功能在衰老过程中多年来所假定的那样不起作用呢?一个关键的考虑因素是,实验室条件下的实验对于在自然不确定条件下发生的生理过程可能具有误导性。在我们摒弃衰老的线粒体假说之前,需要针对该假说进行更多的实地实验。幸运的是,新兴技术使此类实验比以往任何时候都更有可能实现。