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高分辨率呼吸测定法——衰老研究中的一种现代工具。

High-resolution respirometry--a modern tool in aging research.

作者信息

Hütter E, Unterluggauer H, Garedew A, Jansen-Dürr P, Gnaiger E

机构信息

Department of Molecular Cell Biology, Institute for Biomedical Aging Research of the Austrian Academy of Sciences, Rennweg 10, Innsbruck, Austria.

出版信息

Exp Gerontol. 2006 Jan;41(1):103-9. doi: 10.1016/j.exger.2005.09.011. Epub 2005 Nov 23.

Abstract

Alterations in mitochondrial function are believed to play a major role in aging processes in many species, including fungi and animals, and increased oxidative stress is considered a major consequence of altered mitochondrial function. In support of this theory, a lot of correlative evidence has been collected, suggesting that changes in mitochondrial DNA accumulate with age in certain tissues. Furthermore, genetic experiments from lower eukaryotic model organisms, indicate a strong correlative link between increased resistance to oxidative stress and an extended lifespan; in addition, limited experimental evidence suggests that the inhibition of mitochondrial function by selected pharmacologically active compounds can extend lifespan in certain species. However, changes in mitochondrial function may affect aging in a different way in various tissues, and a clear statement about the role of mitochondrial deterioration during physiological aging is missing for most if not all species. At this point, respirometric analyses of mitochondrial function provide a tool to study age-associated changes in mitochondrial respiratory chain function and mitochondrial ATP production within living cells and isolated mitochondria. In the recent years, new instruments have been developed, which allow for an unprecedented high-resolution respirometry, which enables us to determine many parameters of mitochondrial function in routine assays using small samples of biological material. It is conceivable that this technology will become an important tool for all those, who are interested in experimentally addressing the mitochondrial theory of aging. In this article, we provide a synopsis of traditional respirometry and the advances of modern high-resolution respirometry, and discuss how future applications of this technology to recently established experimental models in aging research may provide exciting new insights into the role of mitochondria in the aging process.

摘要

线粒体功能的改变被认为在包括真菌和动物在内的许多物种的衰老过程中起主要作用,而氧化应激增加被认为是线粒体功能改变的主要后果。支持这一理论的是,已经收集了大量相关证据,表明线粒体DNA的变化在某些组织中会随着年龄的增长而积累。此外,来自低等真核模式生物的遗传学实验表明,对氧化应激的抵抗力增强与寿命延长之间存在很强的相关性;此外,有限的实验证据表明,某些具有药理活性的化合物对线粒体功能的抑制作用可以延长某些物种的寿命。然而,线粒体功能的变化在不同组织中可能以不同方式影响衰老,而且对于大多数(如果不是所有)物种来说,关于生理衰老过程中线粒体退化作用的明确表述尚付阙如。此时,线粒体功能的呼吸测定分析为研究活细胞和分离线粒体中线粒体呼吸链功能和线粒体ATP产生的年龄相关变化提供了一种工具。近年来,已经开发出了新的仪器,这些仪器能够实现前所未有的高分辨率呼吸测定,使我们能够在使用少量生物材料样本的常规检测中确定线粒体功能的许多参数。可以想象,这项技术将成为所有对通过实验验证衰老线粒体理论感兴趣的人的重要工具。在本文中,我们概述了传统呼吸测定法和现代高分辨率呼吸测定法的进展,并讨论了该技术未来在衰老研究中最新建立的实验模型中的应用如何能够为线粒体在衰老过程中的作用提供令人兴奋的新见解。

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