In animal mitochondria, the four electron reduction of molecular oxygen to produce water at respiratory complex IV is the terminal step in substrate oxidation. However, respiratory complexes I, II, and III can participate in the single electron reduction of oxygen to produce the radical species superoxide. This progenitor reactive oxygen species (ROS) participates in a number of reactions that generate other ROS. These molecules may react with, and damage, intracellular macromolecules, leading to cellular dysfunction. Mitochondrial ROS production is often considered from this perspective of macromolecular damage and is central to the "oxidative damage theory of aging", which suggests the accumulation of oxidative damage in animal cells underlies the aging phenotype and limits lifespan. In this review, we discuss some experimental results accumulated over the past decade that are inconsistent with this theory. A limitation of the theory is that it presupposes mitochondrial ROS are inherently harmful. However, it is increasingly apparent that some basic cellular functions are physiologically regulated by normal levels of mitochondrial ROS. For example, cell growth and division, the apoptotic pathway, and mitochondrial fusion-fission dynamics all appear to be redox-regulated by mitochondrial ROS and perhaps the matrix manganese superoxide dismutase (MnSOD). Therefore, it is less clear how the balance between ROS regulation of normal cellular activities and ROS-mediated macromolecular damage is maintained and how this relates to aging and longevity in animals. Résumé :Dans les mitochondries animales, la réduction à quatre électrons de l'oxygène moléculaire pour produire de l'eau au complexe respiratoire IV est l'étape terminale de l'oxydation du substrat. Toutefois, les complexes respiratoires I, II et III peuvent participer à la réduction à un seul électron de l'oxygène pour produire le superoxyde radicalaire. Cette forme réactive de l'oxygène (FRO) précurseur intervient dans diverses réactions qui génèrent d'autres FRO. Ces molécules peuvent réagir avec des macromolécules intracellulaires et les endommager, menant ainsi à un dysfonctionnement cellulaire. La production de FRO mitochondriales est souvent considérée du point de vue des dommages macromoléculaires et occupe une place centrale dans la théorie du vieillissement découlant des dommages oxydatifs, qui postule que l'accumulation de dommages oxydatifs dans les cellules animales sous-tend le phénotype du vieillissement et limite la durée de vie. Dans la présente synthèse, nous abordons certains résultats expérimentaux accumulés au cours de la dernière décennie qui sont incompatibles avec cette théorie. Une des limites de la théorie est qu'elle présume que les FRO mitochondriales sont nécessairement néfastes. Il appert toutefois de plus en plus que des concentrations normales de FRO mitochondriales assurent une régulation physiologique de certaines fonctions cellulaires de base. Par exemple, la croissance et la division cellulaires, le mécanisme apoptotique et l...

Discovering key cellular and molecular traits that promote longevity is a major goal of aging and longevity research. One experimental strategy is to determine which traits have been selected during the evolution of longevity in naturally long-lived animal species. This comparative approach has been applied to lifespan research for nearly four decades, yielding hundreds of datasets describing aspects of cell and molecular biology hypothesized to relate to animal longevity. Here, we introduce a Comparative Cellular and Molecular Biology of Longevity Database, available at ( http://genomics.brocku.ca/ccmbl/ ), as a compendium of comparative cell and molecular data presented in the context of longevity. This open access database will facilitate the meta-analysis of amalgamated datasets using standardized maximum lifespan (MLSP) data (from AnAge). The first edition contains over 800 data records describing experimental measurements of cellular stress resistance, reactive oxygen species metabolism, membrane composition, protein homeostasis, and genome homeostasis as they relate to vertebrate species MLSP. The purpose of this review is to introduce the database and briefly demonstrate its use in the meta-analysis of combined datasets.