Department of Dermatology, University of Luebeck, Luebeck, Germany.
PLoS One. 2010 Apr 21;5(4):e10206. doi: 10.1371/journal.pone.0010206.
Aging is a multi-factorial process, however, it is generally accepted that reactive oxygen species (ROS) are significant contributors. Mitochondria are important players in the aging process because they produce most of the cellular ROS. Despite the strength of the free-radical hypothesis, the use of free radical scavengers to delay aging has generated mixed results in vertebrate models, and clinical evidence of efficacy is lacking. This is in part due to the production of pro-oxidant metabolites by many antioxidants while scavenging ROS, which counteract their potentially beneficial effects. As such, a more effective approach is to enhance mitochondrial metabolism by reducing electron leakage with attendant reduction of ROS generation. Here, we report on the actions of a novel endogenous indole derivative, indolepropionamide (IPAM), which is similar in structure to melatonin. Our results suggest that IPAM binds to the rate-limiting component of oxidative phosphorylation in complex I of the respiratory chain and acts as a stabilizer of energy metabolism, thereby reducing ROS production. IPAM reversed the age-dependent decline of mitochondrial energetic capacity and increased rotifer lifespan, and it may, in fact, constitute a novel endogenous anti-aging substance of physiological importance.
衰老是一个多因素的过程，但人们普遍认为活性氧（ROS）是一个重要的贡献者。线粒体在衰老过程中起着重要的作用，因为它们产生了大部分的细胞 ROS。尽管自由基假说的力量很强，但使用自由基清除剂来延缓衰老在脊椎动物模型中产生了混合的结果，而且缺乏有效的临床证据。部分原因是许多抗氧化剂在清除 ROS 的同时会产生促氧化剂代谢物，从而抵消了它们潜在的有益作用。因此，一种更有效的方法是通过减少电子泄漏来增强线粒体代谢，从而减少 ROS 的产生。在这里，我们报告了一种新型内源性吲哚衍生物吲哚丙酰胺（IPAM）的作用，它的结构与褪黑素相似。我们的结果表明，IPAM 与呼吸链复合体 I 中氧化磷酸化的限速成分结合，并作为能量代谢的稳定剂，从而减少 ROS 的产生。IPAM 逆转了与年龄相关的线粒体能量能力下降，并延长了轮虫的寿命，它实际上可能构成一种具有生理重要性的新型内源性抗衰老物质。
